INTRODUCTION — Lichen sclerosus (LS) is a chronic, progressive skin disorder characterized by thin, white, wrinkled skin that is itchy and often painful (show picture 1). LS can develop on any skin surface, but usually is localized to the labia minora and/or labia majora (the inner and outer genital lips) and anal region (show figure 1). In 15 to 20 percent of patients, LS lesions develop on other skin surfaces, such as the thighs, breasts, wrists, shoulders, neck, and even the inside the mouth.
Females are most often affected by LS before puberty and during the peri- or postmenopausal period. Men can also develop LS. Although it is not clear exactly how many people have LS, it is estimated between 1 out of 300 and 1 out of 1000 patients referred to dermatologists have LS.
POTENTIAL CAUSES AND RISK FACTORS — The cause of LS is not clear; healthcare providers suspect that a number of factors may be involved.
Genetic factors — LS seems to be more common in some families. People who are genetically predisposed to LS may develop symptoms after experiencing trauma, injury, or sexual abuse.
Disorders of the immune system — People with LS are at a greater risk of developing autoimmune disorders, which develop when the body's immune system mistakenly attacks and injures normal body tissues. These may include some types of thyroid disease, anemia, diabetes, alopecia areata, and vitiligo.
Infections — Researchers have tried to identify an infectious organism as a cause of LS, but no clear data have shown that there is an infectious source [1]. LS is not contagious.
SIGNS AND SYMPTOMS
Feature of LS in women — Some women with LS feel dull, painful discomfort in the vulva, while other women with LS have no symptoms. Several common symptoms of LS include: Vulvar itching — The most common symptom of LS is itching. It may be so severe that it interferes with sleep. Anal itching, fissures, bleeding, and pain (See "Patient information: Anal fissure") Painful sexual intercourse (dyspareunia) — This can occur as a result of repeated cracking of the skin (fissuring) or from narrowing of the vaginal opening due to scarring.
Typically, women with LS have thin, white, wrinkled skin on the labia minora and/or labia majora, often extending down and around the anus (show figure 1). Purple-colored areas of bruising may be seen. Cracks (also known as fissures) may form in the skin in the area around the anus, the labia, and the clitoris. The vaginal opening may appear yellow and waxy. Relatively minor rubbing or sex may lead to bleeding due to the fragility of the involved skin.
If lichen sclerosus is not treated, it may progress and change the appearance and structure of the genital area as the outer and inner lips of the vulva fuse (stick together) and bury the clitoris (show picture 2). The opening of the vagina can become narrowed, and cracks, fissures, and thickened, scarred skin in the genital and anal area can make sexual intercourse or genital examination painful. LS does not affect the inner reproductive organs, such as the vagina and uterus.
LS may also cause lesions to occur in areas outside the genitals, especially the upper body, breasts, and upper arms. These lesions tend to be white, flat or raised, and are not as itchy as the affected skin of the genitals and anus.
Features of LS in men — In men, lichen sclerosus may appear on the head of the penis. Men who develop lichen sclerosus are usually uncircumcised (they have not had the foreskin of the penis removed), and the foreskin can become tight, shrunken, and scarred over the head of the penis. Men with lichen sclerosus may also have problems pulling back the foreskin and may experience decreased sensation at the tip of the penis, painful erections, and problems with urination [2].
DIAGNOSIS — Providers typically use the following methods to diagnose lichen sclerosus.
History and physical examination — A medical history and examination of the vulvar and anal areas will be done, looking for the signs and symptoms of lichen sclerosus.
Biopsy — To confirm a suspected diagnosis of lichen sclerosus, a biopsy is always recommended. A small piece of the affected skin will be removed and examined with a microscope.
Excluding other conditions — Tests may be done to exclude other conditions that could cause symptoms similar to those of lichen sclerosus, such as: Lichen planus (a skin disease that can also cause itching and fusing of genital skin). Lichen planus can occur together with lichen sclerosus. Low estrogen level (a lack of the hormone estrogen can rarely cause fusing of genital skin but is often the cause of painful intercourse) Vitiligo (a disorder that can cause white skin patches similar to those of lichen sclerosus). Vitiligo can occur together with lichen sclerosus. Pemphigoid (a blistering skin disorder that also causes scarring of the vulva) is extremely rare. Hemorrhoids (which can also cause cracks in the skin of the anus)
LS and cancer — Women with LS affecting the vulva are at increased risk for developing vulvar cancer. In some cases, women may be diagnosed with both LS and cancer at the same time, even though they had no symptoms. For this reason, the skin of patients with vulvar LS should be examined at least yearly, but women should examine themselves regularly for lumps or sores that do not heal. Biopsy should be performed if there are thickened areas that fails to thin with treatment or there are persistently open or nonresolving lesions. LS lesions outside the genital area are not associated with an increased risk of cancer.
Men with LS that affects the skin of the penis have an increased risk of penile cancer.
TREATMENT — The goals of treatment of LS are to relieve bothersome symptoms and to prevent the condition from worsening. A clinician may recommend medication for the physical symptoms, and may refer the patient for support and therapy for other issues associated with the condition, such as problems with sexual functioning.
Most patients with LS, even those without noticeable symptoms, need to use medication on a regular and ongoing basis.
Patients who are diagnosed with LS should talk to their clinician about: The lifelong and potentially progressive nature of LS; appropriate treatment can stop progression Ways to manage the condition The increased risk of vulvar cancer and the need for ongoing monitoring How to keep the genital area healthy and avoid scratching (show table 1)
Depending on the severity of the condition, a healthcare provider may recommend one or more of the following treatments: Topical steroid ointments reduce inflammation and itching. Steroid creams should be avoided because they contain ingredients that irritate the skin. Generic formulations are less desirable due to variations in the ingredients that may be less effective and more irritating. Steroid injections, especially if topical steroids are not effective Short-term retinoid treatments, which are derived from vitamin A, reduce scarring and inflammation, but are reserved for complicated cases. Tacrolimus ointment and/or pimecrolimus cream can be used to reduce itching, inflammation, and redness, but these medications have not been extensively studied and are not proven to stop scarring [3]. Oral or topical tricyclic antidepressants (TCAs) are sometimes recommended for vulvar pain that persists despite topical steroids. When used orally, the dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce pain perception when used in low doses, but the exact mechanism of their benefit is unknown.
TCAs commonly used for pain managment include amitriptyline, desipramine, and nortriptyline. Patients beginning TCAs commonly experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are taken in the evening. TCAs are generally started in low doses and inreased gradually. Their full effect may not be seen for weeks to months.
Surgery is not routinely used to treat LS because lichen sclerosus tends to recur after the skin heals. However, patients whose genital tissues have grown together may have surgery to separate the fused tissues. Recurrence of the scarring occurs frequently. Limited local excision (removal of the affected tissues) can cure vulvar cancer if it is detected early when the area is small.
Men who have lichen sclerosus are generally treated with circumcision, which removes the foreskin of the penis. After circumcision, LS does not usually come back.
WHAT PATIENTS CAN EXPECT — The good news for patients who have been diagnosed with lichen sclerosus is that treatments such as topical steroid ointments are very effective. In one study of 377 patients (74 girls and 253 women), 96 percent of patients showed improvement in their LS symptoms, and 66 percent of patients had relief of all LS symptoms. Thus, early treatment of LS with topical steroids could prevent scarring. However, the likelihood of LS symptom improvement depended upon the patient's age; younger patients have a greater chance for relief of symptoms [4,5]. Regardless of age, follow up in necessary throughout the lifetime.
SUMMARY Lichen sclerosus (LS) is a chronic skin disorder that can develop on any skin surface, but most often affects the genital and anal regions. Although the cause of LS is unclear, the disorder seems to be more common in certain families, suggesting a genetic component. LS is not caused by an infection and it is not contagious. (See "Potential causes and risk factors" above). Symptoms of LS in women may include pain or itching in the vulvar and/or anal area, and the development of thin, white, wrinkled skin on and around the labia. Bruising or cracks (fissures) may also appear, and the fragile skin may bleed with rubbing or sexual activity. In men, LS can develop on the head of the penis, and usually affects the foreskin of uncircumcised males. (See "Signs and symptoms" above). If LS is not treated, it may worsen and cause permanent changes to the genitals. To diagnose LS, a healthcare provider conducts a medical history and physical examination; a biopsy can confirm the diagnosis and rule out other conditions that cause similar symptoms. Patients with LS affecting the genitals are at increased risk for developing cancer, and should be examined regularly for changes. (See "Diagnosis" above). The goals of therapy of LS are to reduce symptoms and prevent the condition from progressing; most patients find that their symptoms improve with treatment over time. Steroid ointments or injections can help reduce inflammation and itching; pain may be treated with medication. (See "Treatment" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Academy of Dermatology
(www.aad.org)
American Urological Association
(www.auanet.org)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(www.niams.nih.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Lichen Sclerosus Support Group
(www.lichensclerosus.org)
National Vulvodynia Association
(www.nva.org)
[2-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Funaro, D. Lichen sclerosus: a review and practical approach. Dermatol Ther 2004; 17:28.
2. Questions and Answers about Lichen Sclerosus. National Institute of Arthritis and Musculoskeletal and Skin Diseases 2004. www.niams.nih.gov/hi/topics/lichen/lichen.htm (Accessed 8/4/06).
3. Kunstfeld, R, Kirnbauer, R, Stingl, G, Karlhofer, FM. Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139:850.
4. Cooper, SM, Gao, XH, Powell, JJ, Wojnarowska, F. Does treatment of vulvar lichen sclerosus influence its prognosis?. Arch Dermatol 2004; 140:702.
5. Renaud-Vilmer, C, Cavelier-Balloy, B, Porcher, R, Dubertret, L. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004; 140:709.
Monday, October 15, 2007
Lichen sclerosus
INTRODUCTION — Lichen sclerosus (LS) is a chronic, progressive skin disorder characterized by thin, white, wrinkled skin that is itchy and often painful (show picture 1). LS can develop on any skin surface, but usually is localized to the labia minora and/or labia majora (the inner and outer genital lips) and anal region (show figure 1). In 15 to 20 percent of patients, LS lesions develop on other skin surfaces, such as the thighs, breasts, wrists, shoulders, neck, and even the inside the mouth.
Females are most often affected by LS before puberty and during the peri- or postmenopausal period. Men can also develop LS. Although it is not clear exactly how many people have LS, it is estimated between 1 out of 300 and 1 out of 1000 patients referred to dermatologists have LS.
POTENTIAL CAUSES AND RISK FACTORS — The cause of LS is not clear; healthcare providers suspect that a number of factors may be involved.
Genetic factors — LS seems to be more common in some families. People who are genetically predisposed to LS may develop symptoms after experiencing trauma, injury, or sexual abuse.
Disorders of the immune system — People with LS are at a greater risk of developing autoimmune disorders, which develop when the body's immune system mistakenly attacks and injures normal body tissues. These may include some types of thyroid disease, anemia, diabetes, alopecia areata, and vitiligo.
Infections — Researchers have tried to identify an infectious organism as a cause of LS, but no clear data have shown that there is an infectious source [1]. LS is not contagious.
SIGNS AND SYMPTOMS
Feature of LS in women — Some women with LS feel dull, painful discomfort in the vulva, while other women with LS have no symptoms. Several common symptoms of LS include: Vulvar itching — The most common symptom of LS is itching. It may be so severe that it interferes with sleep. Anal itching, fissures, bleeding, and pain (See "Patient information: Anal fissure") Painful sexual intercourse (dyspareunia) — This can occur as a result of repeated cracking of the skin (fissuring) or from narrowing of the vaginal opening due to scarring.
Typically, women with LS have thin, white, wrinkled skin on the labia minora and/or labia majora, often extending down and around the anus (show figure 1). Purple-colored areas of bruising may be seen. Cracks (also known as fissures) may form in the skin in the area around the anus, the labia, and the clitoris. The vaginal opening may appear yellow and waxy. Relatively minor rubbing or sex may lead to bleeding due to the fragility of the involved skin.
If lichen sclerosus is not treated, it may progress and change the appearance and structure of the genital area as the outer and inner lips of the vulva fuse (stick together) and bury the clitoris (show picture 2). The opening of the vagina can become narrowed, and cracks, fissures, and thickened, scarred skin in the genital and anal area can make sexual intercourse or genital examination painful. LS does not affect the inner reproductive organs, such as the vagina and uterus.
LS may also cause lesions to occur in areas outside the genitals, especially the upper body, breasts, and upper arms. These lesions tend to be white, flat or raised, and are not as itchy as the affected skin of the genitals and anus.
Features of LS in men — In men, lichen sclerosus may appear on the head of the penis. Men who develop lichen sclerosus are usually uncircumcised (they have not had the foreskin of the penis removed), and the foreskin can become tight, shrunken, and scarred over the head of the penis. Men with lichen sclerosus may also have problems pulling back the foreskin and may experience decreased sensation at the tip of the penis, painful erections, and problems with urination [2].
DIAGNOSIS — Providers typically use the following methods to diagnose lichen sclerosus.
History and physical examination — A medical history and examination of the vulvar and anal areas will be done, looking for the signs and symptoms of lichen sclerosus.
Biopsy — To confirm a suspected diagnosis of lichen sclerosus, a biopsy is always recommended. A small piece of the affected skin will be removed and examined with a microscope.
Excluding other conditions — Tests may be done to exclude other conditions that could cause symptoms similar to those of lichen sclerosus, such as: Lichen planus (a skin disease that can also cause itching and fusing of genital skin). Lichen planus can occur together with lichen sclerosus. Low estrogen level (a lack of the hormone estrogen can rarely cause fusing of genital skin but is often the cause of painful intercourse) Vitiligo (a disorder that can cause white skin patches similar to those of lichen sclerosus). Vitiligo can occur together with lichen sclerosus. Pemphigoid (a blistering skin disorder that also causes scarring of the vulva) is extremely rare. Hemorrhoids (which can also cause cracks in the skin of the anus)
LS and cancer — Women with LS affecting the vulva are at increased risk for developing vulvar cancer. In some cases, women may be diagnosed with both LS and cancer at the same time, even though they had no symptoms. For this reason, the skin of patients with vulvar LS should be examined at least yearly, but women should examine themselves regularly for lumps or sores that do not heal. Biopsy should be performed if there are thickened areas that fails to thin with treatment or there are persistently open or nonresolving lesions. LS lesions outside the genital area are not associated with an increased risk of cancer.
Men with LS that affects the skin of the penis have an increased risk of penile cancer.
TREATMENT — The goals of treatment of LS are to relieve bothersome symptoms and to prevent the condition from worsening. A clinician may recommend medication for the physical symptoms, and may refer the patient for support and therapy for other issues associated with the condition, such as problems with sexual functioning.
Most patients with LS, even those without noticeable symptoms, need to use medication on a regular and ongoing basis.
Patients who are diagnosed with LS should talk to their clinician about: The lifelong and potentially progressive nature of LS; appropriate treatment can stop progression Ways to manage the condition The increased risk of vulvar cancer and the need for ongoing monitoring How to keep the genital area healthy and avoid scratching (show table 1)
Depending on the severity of the condition, a healthcare provider may recommend one or more of the following treatments: Topical steroid ointments reduce inflammation and itching. Steroid creams should be avoided because they contain ingredients that irritate the skin. Generic formulations are less desirable due to variations in the ingredients that may be less effective and more irritating. Steroid injections, especially if topical steroids are not effective Short-term retinoid treatments, which are derived from vitamin A, reduce scarring and inflammation, but are reserved for complicated cases. Tacrolimus ointment and/or pimecrolimus cream can be used to reduce itching, inflammation, and redness, but these medications have not been extensively studied and are not proven to stop scarring [3]. Oral or topical tricyclic antidepressants (TCAs) are sometimes recommended for vulvar pain that persists despite topical steroids. When used orally, the dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce pain perception when used in low doses, but the exact mechanism of their benefit is unknown.
TCAs commonly used for pain managment include amitriptyline, desipramine, and nortriptyline. Patients beginning TCAs commonly experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are taken in the evening. TCAs are generally started in low doses and inreased gradually. Their full effect may not be seen for weeks to months.
Surgery is not routinely used to treat LS because lichen sclerosus tends to recur after the skin heals. However, patients whose genital tissues have grown together may have surgery to separate the fused tissues. Recurrence of the scarring occurs frequently. Limited local excision (removal of the affected tissues) can cure vulvar cancer if it is detected early when the area is small.
Men who have lichen sclerosus are generally treated with circumcision, which removes the foreskin of the penis. After circumcision, LS does not usually come back.
WHAT PATIENTS CAN EXPECT — The good news for patients who have been diagnosed with lichen sclerosus is that treatments such as topical steroid ointments are very effective. In one study of 377 patients (74 girls and 253 women), 96 percent of patients showed improvement in their LS symptoms, and 66 percent of patients had relief of all LS symptoms. Thus, early treatment of LS with topical steroids could prevent scarring. However, the likelihood of LS symptom improvement depended upon the patient's age; younger patients have a greater chance for relief of symptoms [4,5]. Regardless of age, follow up in necessary throughout the lifetime.
SUMMARY Lichen sclerosus (LS) is a chronic skin disorder that can develop on any skin surface, but most often affects the genital and anal regions. Although the cause of LS is unclear, the disorder seems to be more common in certain families, suggesting a genetic component. LS is not caused by an infection and it is not contagious. (See "Potential causes and risk factors" above). Symptoms of LS in women may include pain or itching in the vulvar and/or anal area, and the development of thin, white, wrinkled skin on and around the labia. Bruising or cracks (fissures) may also appear, and the fragile skin may bleed with rubbing or sexual activity. In men, LS can develop on the head of the penis, and usually affects the foreskin of uncircumcised males. (See "Signs and symptoms" above). If LS is not treated, it may worsen and cause permanent changes to the genitals. To diagnose LS, a healthcare provider conducts a medical history and physical examination; a biopsy can confirm the diagnosis and rule out other conditions that cause similar symptoms. Patients with LS affecting the genitals are at increased risk for developing cancer, and should be examined regularly for changes. (See "Diagnosis" above). The goals of therapy of LS are to reduce symptoms and prevent the condition from progressing; most patients find that their symptoms improve with treatment over time. Steroid ointments or injections can help reduce inflammation and itching; pain may be treated with medication. (See "Treatment" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Academy of Dermatology
(www.aad.org)
American Urological Association
(www.auanet.org)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(www.niams.nih.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Lichen Sclerosus Support Group
(www.lichensclerosus.org)
National Vulvodynia Association
(www.nva.org)
[2-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Funaro, D. Lichen sclerosus: a review and practical approach. Dermatol Ther 2004; 17:28.
2. Questions and Answers about Lichen Sclerosus. National Institute of Arthritis and Musculoskeletal and Skin Diseases 2004. www.niams.nih.gov/hi/topics/lichen/lichen.htm (Accessed 8/4/06).
3. Kunstfeld, R, Kirnbauer, R, Stingl, G, Karlhofer, FM. Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139:850.
4. Cooper, SM, Gao, XH, Powell, JJ, Wojnarowska, F. Does treatment of vulvar lichen sclerosus influence its prognosis?. Arch Dermatol 2004; 140:702.
5. Renaud-Vilmer, C, Cavelier-Balloy, B, Porcher, R, Dubertret, L. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004; 140:709.
Females are most often affected by LS before puberty and during the peri- or postmenopausal period. Men can also develop LS. Although it is not clear exactly how many people have LS, it is estimated between 1 out of 300 and 1 out of 1000 patients referred to dermatologists have LS.
POTENTIAL CAUSES AND RISK FACTORS — The cause of LS is not clear; healthcare providers suspect that a number of factors may be involved.
Genetic factors — LS seems to be more common in some families. People who are genetically predisposed to LS may develop symptoms after experiencing trauma, injury, or sexual abuse.
Disorders of the immune system — People with LS are at a greater risk of developing autoimmune disorders, which develop when the body's immune system mistakenly attacks and injures normal body tissues. These may include some types of thyroid disease, anemia, diabetes, alopecia areata, and vitiligo.
Infections — Researchers have tried to identify an infectious organism as a cause of LS, but no clear data have shown that there is an infectious source [1]. LS is not contagious.
SIGNS AND SYMPTOMS
Feature of LS in women — Some women with LS feel dull, painful discomfort in the vulva, while other women with LS have no symptoms. Several common symptoms of LS include: Vulvar itching — The most common symptom of LS is itching. It may be so severe that it interferes with sleep. Anal itching, fissures, bleeding, and pain (See "Patient information: Anal fissure") Painful sexual intercourse (dyspareunia) — This can occur as a result of repeated cracking of the skin (fissuring) or from narrowing of the vaginal opening due to scarring.
Typically, women with LS have thin, white, wrinkled skin on the labia minora and/or labia majora, often extending down and around the anus (show figure 1). Purple-colored areas of bruising may be seen. Cracks (also known as fissures) may form in the skin in the area around the anus, the labia, and the clitoris. The vaginal opening may appear yellow and waxy. Relatively minor rubbing or sex may lead to bleeding due to the fragility of the involved skin.
If lichen sclerosus is not treated, it may progress and change the appearance and structure of the genital area as the outer and inner lips of the vulva fuse (stick together) and bury the clitoris (show picture 2). The opening of the vagina can become narrowed, and cracks, fissures, and thickened, scarred skin in the genital and anal area can make sexual intercourse or genital examination painful. LS does not affect the inner reproductive organs, such as the vagina and uterus.
LS may also cause lesions to occur in areas outside the genitals, especially the upper body, breasts, and upper arms. These lesions tend to be white, flat or raised, and are not as itchy as the affected skin of the genitals and anus.
Features of LS in men — In men, lichen sclerosus may appear on the head of the penis. Men who develop lichen sclerosus are usually uncircumcised (they have not had the foreskin of the penis removed), and the foreskin can become tight, shrunken, and scarred over the head of the penis. Men with lichen sclerosus may also have problems pulling back the foreskin and may experience decreased sensation at the tip of the penis, painful erections, and problems with urination [2].
DIAGNOSIS — Providers typically use the following methods to diagnose lichen sclerosus.
History and physical examination — A medical history and examination of the vulvar and anal areas will be done, looking for the signs and symptoms of lichen sclerosus.
Biopsy — To confirm a suspected diagnosis of lichen sclerosus, a biopsy is always recommended. A small piece of the affected skin will be removed and examined with a microscope.
Excluding other conditions — Tests may be done to exclude other conditions that could cause symptoms similar to those of lichen sclerosus, such as: Lichen planus (a skin disease that can also cause itching and fusing of genital skin). Lichen planus can occur together with lichen sclerosus. Low estrogen level (a lack of the hormone estrogen can rarely cause fusing of genital skin but is often the cause of painful intercourse) Vitiligo (a disorder that can cause white skin patches similar to those of lichen sclerosus). Vitiligo can occur together with lichen sclerosus. Pemphigoid (a blistering skin disorder that also causes scarring of the vulva) is extremely rare. Hemorrhoids (which can also cause cracks in the skin of the anus)
LS and cancer — Women with LS affecting the vulva are at increased risk for developing vulvar cancer. In some cases, women may be diagnosed with both LS and cancer at the same time, even though they had no symptoms. For this reason, the skin of patients with vulvar LS should be examined at least yearly, but women should examine themselves regularly for lumps or sores that do not heal. Biopsy should be performed if there are thickened areas that fails to thin with treatment or there are persistently open or nonresolving lesions. LS lesions outside the genital area are not associated with an increased risk of cancer.
Men with LS that affects the skin of the penis have an increased risk of penile cancer.
TREATMENT — The goals of treatment of LS are to relieve bothersome symptoms and to prevent the condition from worsening. A clinician may recommend medication for the physical symptoms, and may refer the patient for support and therapy for other issues associated with the condition, such as problems with sexual functioning.
Most patients with LS, even those without noticeable symptoms, need to use medication on a regular and ongoing basis.
Patients who are diagnosed with LS should talk to their clinician about: The lifelong and potentially progressive nature of LS; appropriate treatment can stop progression Ways to manage the condition The increased risk of vulvar cancer and the need for ongoing monitoring How to keep the genital area healthy and avoid scratching (show table 1)
Depending on the severity of the condition, a healthcare provider may recommend one or more of the following treatments: Topical steroid ointments reduce inflammation and itching. Steroid creams should be avoided because they contain ingredients that irritate the skin. Generic formulations are less desirable due to variations in the ingredients that may be less effective and more irritating. Steroid injections, especially if topical steroids are not effective Short-term retinoid treatments, which are derived from vitamin A, reduce scarring and inflammation, but are reserved for complicated cases. Tacrolimus ointment and/or pimecrolimus cream can be used to reduce itching, inflammation, and redness, but these medications have not been extensively studied and are not proven to stop scarring [3]. Oral or topical tricyclic antidepressants (TCAs) are sometimes recommended for vulvar pain that persists despite topical steroids. When used orally, the dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce pain perception when used in low doses, but the exact mechanism of their benefit is unknown.
TCAs commonly used for pain managment include amitriptyline, desipramine, and nortriptyline. Patients beginning TCAs commonly experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are taken in the evening. TCAs are generally started in low doses and inreased gradually. Their full effect may not be seen for weeks to months.
Surgery is not routinely used to treat LS because lichen sclerosus tends to recur after the skin heals. However, patients whose genital tissues have grown together may have surgery to separate the fused tissues. Recurrence of the scarring occurs frequently. Limited local excision (removal of the affected tissues) can cure vulvar cancer if it is detected early when the area is small.
Men who have lichen sclerosus are generally treated with circumcision, which removes the foreskin of the penis. After circumcision, LS does not usually come back.
WHAT PATIENTS CAN EXPECT — The good news for patients who have been diagnosed with lichen sclerosus is that treatments such as topical steroid ointments are very effective. In one study of 377 patients (74 girls and 253 women), 96 percent of patients showed improvement in their LS symptoms, and 66 percent of patients had relief of all LS symptoms. Thus, early treatment of LS with topical steroids could prevent scarring. However, the likelihood of LS symptom improvement depended upon the patient's age; younger patients have a greater chance for relief of symptoms [4,5]. Regardless of age, follow up in necessary throughout the lifetime.
SUMMARY Lichen sclerosus (LS) is a chronic skin disorder that can develop on any skin surface, but most often affects the genital and anal regions. Although the cause of LS is unclear, the disorder seems to be more common in certain families, suggesting a genetic component. LS is not caused by an infection and it is not contagious. (See "Potential causes and risk factors" above). Symptoms of LS in women may include pain or itching in the vulvar and/or anal area, and the development of thin, white, wrinkled skin on and around the labia. Bruising or cracks (fissures) may also appear, and the fragile skin may bleed with rubbing or sexual activity. In men, LS can develop on the head of the penis, and usually affects the foreskin of uncircumcised males. (See "Signs and symptoms" above). If LS is not treated, it may worsen and cause permanent changes to the genitals. To diagnose LS, a healthcare provider conducts a medical history and physical examination; a biopsy can confirm the diagnosis and rule out other conditions that cause similar symptoms. Patients with LS affecting the genitals are at increased risk for developing cancer, and should be examined regularly for changes. (See "Diagnosis" above). The goals of therapy of LS are to reduce symptoms and prevent the condition from progressing; most patients find that their symptoms improve with treatment over time. Steroid ointments or injections can help reduce inflammation and itching; pain may be treated with medication. (See "Treatment" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Academy of Dermatology
(www.aad.org)
American Urological Association
(www.auanet.org)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(www.niams.nih.gov)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Lichen Sclerosus Support Group
(www.lichensclerosus.org)
National Vulvodynia Association
(www.nva.org)
[2-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Funaro, D. Lichen sclerosus: a review and practical approach. Dermatol Ther 2004; 17:28.
2. Questions and Answers about Lichen Sclerosus. National Institute of Arthritis and Musculoskeletal and Skin Diseases 2004. www.niams.nih.gov/hi/topics/lichen/lichen.htm (Accessed 8/4/06).
3. Kunstfeld, R, Kirnbauer, R, Stingl, G, Karlhofer, FM. Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139:850.
4. Cooper, SM, Gao, XH, Powell, JJ, Wojnarowska, F. Does treatment of vulvar lichen sclerosus influence its prognosis?. Arch Dermatol 2004; 140:702.
5. Renaud-Vilmer, C, Cavelier-Balloy, B, Porcher, R, Dubertret, L. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004; 140:709.
Sunday, October 14, 2007
Infertility treatment with clomiphene (Clomid® or Serophene®)
INTRODUCTION — Infertility is defined as a couple's inability to become pregnant after one year of unprotected intercourse. In any given year, about 15 percent of couples in North America and Europe who are trying to conceive are infertile.
The fertility of a couple depends upon several factors in both the male and female partner. Among all cases of infertility, about 20 percent can be traced to male factors, 38 percent can be traced to female factors, 27 percent can be traced to factors in both the male and female partners, and 15 percent cannot be traced to obvious factors in either partner.
When infertility occurs, the male and female partners are evaluated to determine the cause and best treatment options. For couples where the woman is not ovulating regularly, one treatment option involves the female partner taking an oral medication, clomiphene citrate (Clomid® or Serophene®).
This topic will review the use of clomiphene in the treatment of female infertility. The evaluation of the infertile couple, as well as the causes and treatment of male infertility, is discussed separately. (See "Patient information: Evaluation of the infertile couple" and see "Patient information: Treatment of infertility in men").
OVULATION — To understand why and how clomiphene is used, it is necessary to understand normal ovulation. Normally, a woman's ovaries produce one egg every 24 to 35 days. Ovulation usually occurs about 12 to 14 days before the next menstrual period (show figure 1). A woman's best chances for becoming pregnant occurs around the day of ovulation and two to four days before ovulation. This would be approximately 10 to 14 days after the first day of the menstrual cycle (day 1 of the menstrual cycle is the first day of bleeding).
A complex balance of hormones is required to stimulate ovulation, changes in hormone levels can cause ovulation to occur irregularly or to temporarily stop. A woman who has absent or irregular ovulation is said to have anovulation or oligoovulation.
There are several types of anovulation, as defined by the World Health Organization (WHO). These types are organized by the woman's blood level of follicle stimulating hormone (FSH) and estrogen (estradiol). FSH is a hormone produced by the pituitary (a gland within the brain) and estrogen is a hormone produced by the ovaries. The levels of these hormones change throughout the menstrual cycle, as shown in figure 1 (show figure 1).
Women who are most likely to respond to clomiphene include those who do not have an excessively elevated level of FSH (demonstrating a decrease in the number of eggs within the ovaries) and who have uterine bleeding when treated with a progestin (WHO class 2) (show table 1). This includes women with polycystic ovary syndrome.
WHAT IS CLOMIPHENE? — Clomiphene is a hormone that acts on the hypothalamus, pituitary gland, and ovary to increase levels of FSH and luteinizing hormone (LH, which is also important in the process of ovulation). An increased level of these hormones improves the chances of growing an ovarian follicle that can then trigger ovulation. In women who ovulate irregularly, approximately 80 percent who take clomiphene will ovulate, and 30 to 40 percent of all women who take clomiphene become pregnant. These numbers apply to women who have taken three cycles of clomiphene.
Pretreatment evaluation — Before any infertility treatment begins, a woman and her partner should be evaluated to be sure that clomiphene is the best treatment. This evaluation may include a complete history and physical examination, a semen analysis (for men), blood testing, and other tests depending upon the individual situation. (See "Patient information: Evaluation of the infertile couple").
Dosing — Clomiphene is usually started on day three, four, or five of the menstrual cycle at a dose of 50 mg once daily for five days. The first day of bleeding is arbitrarily called cycle day one. If the woman does not have regular menstrual cycles (which is usually the situation), she may be given a course of progestin medication to induce a period.
The couple is advised to have intercourse every other day for one week, beginning around day 10 of the clomiphene cycle. The couple may plan intercourse by using an ovulation predictor kit, which uses a urine sample to predict when ovulation is about to occur by measuring the LH level; these are available without a prescription. Most fertility specialists recommend the use of the ovulation predictor kit.
Some clinicians measure the blood level of progesterone one week before the expected menstrual period to determine if ovulation occurred; blood testing may be preferred to ovulation predictor kits because it provides reliable evidence that ovulation occurred (rather than a prediction that ovulation might occur).
Some healthcare providers recommend transvaginal ultrasound monitoring for women undergoing clomiphene treatment. This involves inserting a thin probe into the vagina and using sound waves to view the size and number of developing follicles (which contain an egg).
Use of an ovulation predictor kit, blood testing, and/or ultrasound are not required for women using clomiphene, and testing does not improve pregnancy rates significantly. However, almost all fertility specialists recommend use of an ovulation predictor kit and blood testing to confirm ovulation. Some recommend ultrasound, but this requires more office visits and increases the cost of treatment.
If ovulation does not occur during the first month, the clomiphene dose may be increased. There is no benefit of increasing the clomiphene dose if ovulation occurs, even if pregnancy does not occur. Most pregnancies occur within the first six cycles of using clomiphene, and there is little benefit of continuing clomiphene treatment after six unsuccessful cycles.
Benefits — The benefit of clomiphene is that it is relatively inexpensive and can be used before other, more expensive testing (such as hysterosalpingogram or laparoscopy) or infertility treatments (eg, in vitro fertilization). It does not require monitoring with ultrasound or blood hormone levels, although monitoring may be recommended in some cases. Clomiphene improves the chances of becoming pregnant for most women who ovulate irregularly, and carries a low risk of dangerous side effects.
Risks — Risks of clomiphene therapy include a slightly increased rate of multiple pregnancies; approximately 6 percent of women who use clomiphene have twins, while less than 0.5 percent have triplets or greater. There is a small risk of the ovaries becoming enlarged, although severe enlargement (known as ovarian hyperstimulation syndrome) is rare.
Common side effects of clomiphene include hot flashes, abdominal bloating and pain, nausea and vomiting, and breast tenderness. Visual symptoms such as blurring, double vision, or seeing spots occur in 1 to 2 percent of women, and usually resolve when treatment stops. Mood swings, depression, and headaches can occur, but are rarely serious enough to cause the woman to stop treatment.
There is no increased risk of birth defects, miscarriage, or learning disability in children of women who took clomiphene. There is no increased risk of breast cancer or uterine cancer. There may be a slightly increased risk of ovarian cancer if more than 12 cycles of clomiphene are used.
IMPROVING CLOMIPHENE SUCCESS — Women who do not become pregnant after three cycles of clomiphene may need further testing before continuing with treatment. This may include a hysterosalpingogram, blood testing, and if not previously done, a semen analysis of the male partner. (See "Patient information: Evaluation of the infertile couple").
If these tests are normal and the couple would like to continue with clomiphene treatment, additional interventions may improve success. Depending upon the individual, this may include weight loss or gain, or use of additional medications such as metformin or dexamethasone.
Weight loss — Women who are overweight or obese and who ovulate infrequently often benefit from weight loss as a treatment for their infertility. Overweight is defined as having a body mass index (BMI) greater than 27 kg/m2. To calculate BMI, divide weight in pounds by height in inches; then divide that number by height in inches and multiply by 703. A BMI table may also be used (show table 2A-2B).
Weight loss is an inexpensive and low-risk treatment with no side effects that has been proven to improve the chances of ovulation and pregnancy in women who are overweight. In addition, having a normal or near-normal weight can reduce the risk of complications during pregnancy. Furthermore, achieving and maintaining a weight in the normal range has life-long health benefits. A combination of decreased calorie intake and exercise are recommended to achieve a 5 to 10 percent weight loss. (See "Patient information: Diet and health").
Weight gain — Women who are underweight (defined as a BMI less than 17 kg/m2), have eating disorders (eg, bulimia or anorexia), or participate in strenuous exercise regimens may ovulate irregularly or not at all. These women may be advised to gain weight to a goal BMI of at least 19 kg/m2 (show table 2A-2B), increase calorie intake, and modify exercise habits to include less strenuous activities.
Treatment with human chorionic gonadotropin — Some women who do not have an increase in their LH level midcycle do not ovulate (show figure 1), despite having a normally developed follicle (which contains an egg). These women often benefit from an injection of human chorionic gonadotropin (hCG), which acts like LH to trigger ovulation. Transvaginal ultrasound is used to determine when the follicle is ready, and the woman or her partner can be taught to give the injection at home. Ovulation occurs 36 to 44 hours after the injection, and intercourse can be timed accordingly.
Treatment for insulin resistance — Women with polycystic ovary syndrome who have absent or irregular ovulation are often insulin resistant. Insulin is a hormone produced by the pancreas that functions to break down food into energy. Insulin resistance causes the body to produce excessive amounts of insulin, which leads to elevated levels of other hormones that interfere with ovulation. Treatment of insulin resistance can reduce these hormones, increase the chances of normal ovulation, and improve the chances of responding to clomiphene.
Metformin — Metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®) is a medication that is used in the treatment of type 2 diabetes mellitus. It has also been used to treat insulin resistance in women with polycystic ovary syndrome and infertility if clomiphene treatment and/or weight loss is not successful. Some women who do not ovulate with clomiphene may ovulate with the combination of metformin plus clomiphene.
Metformin is thought to be safe to take while trying to become pregnant, but should be stopped once pregnancy is confirmed.
Glucocorticoid treatment — Women who are anovulatory WHO class 2 (show table 1) and have not ovulated in response to clomiphene treatment may benefit from treatment with clomiphene as well as a glucocorticoid (a type of steroid). Dexamethasone or prednisone are the glucorticoids most commonly used. One regimen is to use a glucocorticoid daily from the start of the treatment cycle through ovulation
CLOMIPHENE FAILURE — If a woman with anovulation does not become pregnant after three to six cycles of clomiphene, other infertility treatments may be considered. These include surgical treatments, ovulation induction with injectable medications and/or in vitro fertilization.
COSTS OF INFERTILITY TREATMENT — The costs of infertility treatments can be high depending upon what tests are required, the type and dose of medication(s) used, and the number of months that it takes to become pregnant. Insurance policies cover the costs of infertility treatment in some areas, although this varies by location and individual insurance policy. At this time, less than half of the states within the U.S. have laws requiring insurers to cover infertility treatment.
More information about a state's laws can be obtained by calling the state Insurance Commissioner's office. More information can also be found by visiting the website for the American Society of Reproductive Medicine (www.asrm.org/Patients/insur.html).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
Resolve: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Use of clomiphene citrate in women. Fertil Steril 2003; 80:1302.
2. Hughes, E, Collins, J, Vandekerckhove, P. Clomiphene citrate for unexplained subfertility in women (Cochrane review). Cochrane Database Syst Rev 2000; :CD000057.
3. Smith, YR, Randolph, JF Jr, Christman, GM, et al. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril 1998; 70:165.
4. Barbieri, RL. Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. Am J Obstet Gynecol 2000; 183:1412.
The fertility of a couple depends upon several factors in both the male and female partner. Among all cases of infertility, about 20 percent can be traced to male factors, 38 percent can be traced to female factors, 27 percent can be traced to factors in both the male and female partners, and 15 percent cannot be traced to obvious factors in either partner.
When infertility occurs, the male and female partners are evaluated to determine the cause and best treatment options. For couples where the woman is not ovulating regularly, one treatment option involves the female partner taking an oral medication, clomiphene citrate (Clomid® or Serophene®).
This topic will review the use of clomiphene in the treatment of female infertility. The evaluation of the infertile couple, as well as the causes and treatment of male infertility, is discussed separately. (See "Patient information: Evaluation of the infertile couple" and see "Patient information: Treatment of infertility in men").
OVULATION — To understand why and how clomiphene is used, it is necessary to understand normal ovulation. Normally, a woman's ovaries produce one egg every 24 to 35 days. Ovulation usually occurs about 12 to 14 days before the next menstrual period (show figure 1). A woman's best chances for becoming pregnant occurs around the day of ovulation and two to four days before ovulation. This would be approximately 10 to 14 days after the first day of the menstrual cycle (day 1 of the menstrual cycle is the first day of bleeding).
A complex balance of hormones is required to stimulate ovulation, changes in hormone levels can cause ovulation to occur irregularly or to temporarily stop. A woman who has absent or irregular ovulation is said to have anovulation or oligoovulation.
There are several types of anovulation, as defined by the World Health Organization (WHO). These types are organized by the woman's blood level of follicle stimulating hormone (FSH) and estrogen (estradiol). FSH is a hormone produced by the pituitary (a gland within the brain) and estrogen is a hormone produced by the ovaries. The levels of these hormones change throughout the menstrual cycle, as shown in figure 1 (show figure 1).
Women who are most likely to respond to clomiphene include those who do not have an excessively elevated level of FSH (demonstrating a decrease in the number of eggs within the ovaries) and who have uterine bleeding when treated with a progestin (WHO class 2) (show table 1). This includes women with polycystic ovary syndrome.
WHAT IS CLOMIPHENE? — Clomiphene is a hormone that acts on the hypothalamus, pituitary gland, and ovary to increase levels of FSH and luteinizing hormone (LH, which is also important in the process of ovulation). An increased level of these hormones improves the chances of growing an ovarian follicle that can then trigger ovulation. In women who ovulate irregularly, approximately 80 percent who take clomiphene will ovulate, and 30 to 40 percent of all women who take clomiphene become pregnant. These numbers apply to women who have taken three cycles of clomiphene.
Pretreatment evaluation — Before any infertility treatment begins, a woman and her partner should be evaluated to be sure that clomiphene is the best treatment. This evaluation may include a complete history and physical examination, a semen analysis (for men), blood testing, and other tests depending upon the individual situation. (See "Patient information: Evaluation of the infertile couple").
Dosing — Clomiphene is usually started on day three, four, or five of the menstrual cycle at a dose of 50 mg once daily for five days. The first day of bleeding is arbitrarily called cycle day one. If the woman does not have regular menstrual cycles (which is usually the situation), she may be given a course of progestin medication to induce a period.
The couple is advised to have intercourse every other day for one week, beginning around day 10 of the clomiphene cycle. The couple may plan intercourse by using an ovulation predictor kit, which uses a urine sample to predict when ovulation is about to occur by measuring the LH level; these are available without a prescription. Most fertility specialists recommend the use of the ovulation predictor kit.
Some clinicians measure the blood level of progesterone one week before the expected menstrual period to determine if ovulation occurred; blood testing may be preferred to ovulation predictor kits because it provides reliable evidence that ovulation occurred (rather than a prediction that ovulation might occur).
Some healthcare providers recommend transvaginal ultrasound monitoring for women undergoing clomiphene treatment. This involves inserting a thin probe into the vagina and using sound waves to view the size and number of developing follicles (which contain an egg).
Use of an ovulation predictor kit, blood testing, and/or ultrasound are not required for women using clomiphene, and testing does not improve pregnancy rates significantly. However, almost all fertility specialists recommend use of an ovulation predictor kit and blood testing to confirm ovulation. Some recommend ultrasound, but this requires more office visits and increases the cost of treatment.
If ovulation does not occur during the first month, the clomiphene dose may be increased. There is no benefit of increasing the clomiphene dose if ovulation occurs, even if pregnancy does not occur. Most pregnancies occur within the first six cycles of using clomiphene, and there is little benefit of continuing clomiphene treatment after six unsuccessful cycles.
Benefits — The benefit of clomiphene is that it is relatively inexpensive and can be used before other, more expensive testing (such as hysterosalpingogram or laparoscopy) or infertility treatments (eg, in vitro fertilization). It does not require monitoring with ultrasound or blood hormone levels, although monitoring may be recommended in some cases. Clomiphene improves the chances of becoming pregnant for most women who ovulate irregularly, and carries a low risk of dangerous side effects.
Risks — Risks of clomiphene therapy include a slightly increased rate of multiple pregnancies; approximately 6 percent of women who use clomiphene have twins, while less than 0.5 percent have triplets or greater. There is a small risk of the ovaries becoming enlarged, although severe enlargement (known as ovarian hyperstimulation syndrome) is rare.
Common side effects of clomiphene include hot flashes, abdominal bloating and pain, nausea and vomiting, and breast tenderness. Visual symptoms such as blurring, double vision, or seeing spots occur in 1 to 2 percent of women, and usually resolve when treatment stops. Mood swings, depression, and headaches can occur, but are rarely serious enough to cause the woman to stop treatment.
There is no increased risk of birth defects, miscarriage, or learning disability in children of women who took clomiphene. There is no increased risk of breast cancer or uterine cancer. There may be a slightly increased risk of ovarian cancer if more than 12 cycles of clomiphene are used.
IMPROVING CLOMIPHENE SUCCESS — Women who do not become pregnant after three cycles of clomiphene may need further testing before continuing with treatment. This may include a hysterosalpingogram, blood testing, and if not previously done, a semen analysis of the male partner. (See "Patient information: Evaluation of the infertile couple").
If these tests are normal and the couple would like to continue with clomiphene treatment, additional interventions may improve success. Depending upon the individual, this may include weight loss or gain, or use of additional medications such as metformin or dexamethasone.
Weight loss — Women who are overweight or obese and who ovulate infrequently often benefit from weight loss as a treatment for their infertility. Overweight is defined as having a body mass index (BMI) greater than 27 kg/m2. To calculate BMI, divide weight in pounds by height in inches; then divide that number by height in inches and multiply by 703. A BMI table may also be used (show table 2A-2B).
Weight loss is an inexpensive and low-risk treatment with no side effects that has been proven to improve the chances of ovulation and pregnancy in women who are overweight. In addition, having a normal or near-normal weight can reduce the risk of complications during pregnancy. Furthermore, achieving and maintaining a weight in the normal range has life-long health benefits. A combination of decreased calorie intake and exercise are recommended to achieve a 5 to 10 percent weight loss. (See "Patient information: Diet and health").
Weight gain — Women who are underweight (defined as a BMI less than 17 kg/m2), have eating disorders (eg, bulimia or anorexia), or participate in strenuous exercise regimens may ovulate irregularly or not at all. These women may be advised to gain weight to a goal BMI of at least 19 kg/m2 (show table 2A-2B), increase calorie intake, and modify exercise habits to include less strenuous activities.
Treatment with human chorionic gonadotropin — Some women who do not have an increase in their LH level midcycle do not ovulate (show figure 1), despite having a normally developed follicle (which contains an egg). These women often benefit from an injection of human chorionic gonadotropin (hCG), which acts like LH to trigger ovulation. Transvaginal ultrasound is used to determine when the follicle is ready, and the woman or her partner can be taught to give the injection at home. Ovulation occurs 36 to 44 hours after the injection, and intercourse can be timed accordingly.
Treatment for insulin resistance — Women with polycystic ovary syndrome who have absent or irregular ovulation are often insulin resistant. Insulin is a hormone produced by the pancreas that functions to break down food into energy. Insulin resistance causes the body to produce excessive amounts of insulin, which leads to elevated levels of other hormones that interfere with ovulation. Treatment of insulin resistance can reduce these hormones, increase the chances of normal ovulation, and improve the chances of responding to clomiphene.
Metformin — Metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®) is a medication that is used in the treatment of type 2 diabetes mellitus. It has also been used to treat insulin resistance in women with polycystic ovary syndrome and infertility if clomiphene treatment and/or weight loss is not successful. Some women who do not ovulate with clomiphene may ovulate with the combination of metformin plus clomiphene.
Metformin is thought to be safe to take while trying to become pregnant, but should be stopped once pregnancy is confirmed.
Glucocorticoid treatment — Women who are anovulatory WHO class 2 (show table 1) and have not ovulated in response to clomiphene treatment may benefit from treatment with clomiphene as well as a glucocorticoid (a type of steroid). Dexamethasone or prednisone are the glucorticoids most commonly used. One regimen is to use a glucocorticoid daily from the start of the treatment cycle through ovulation
CLOMIPHENE FAILURE — If a woman with anovulation does not become pregnant after three to six cycles of clomiphene, other infertility treatments may be considered. These include surgical treatments, ovulation induction with injectable medications and/or in vitro fertilization.
COSTS OF INFERTILITY TREATMENT — The costs of infertility treatments can be high depending upon what tests are required, the type and dose of medication(s) used, and the number of months that it takes to become pregnant. Insurance policies cover the costs of infertility treatment in some areas, although this varies by location and individual insurance policy. At this time, less than half of the states within the U.S. have laws requiring insurers to cover infertility treatment.
More information about a state's laws can be obtained by calling the state Insurance Commissioner's office. More information can also be found by visiting the website for the American Society of Reproductive Medicine (www.asrm.org/Patients/insur.html).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
Resolve: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Use of clomiphene citrate in women. Fertil Steril 2003; 80:1302.
2. Hughes, E, Collins, J, Vandekerckhove, P. Clomiphene citrate for unexplained subfertility in women (Cochrane review). Cochrane Database Syst Rev 2000; :CD000057.
3. Smith, YR, Randolph, JF Jr, Christman, GM, et al. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril 1998; 70:165.
4. Barbieri, RL. Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. Am J Obstet Gynecol 2000; 183:1412.
Infertility treatment with clomiphene (Clomid® or Serophene®)
INTRODUCTION — Infertility is defined as a couple's inability to become pregnant after one year of unprotected intercourse. In any given year, about 15 percent of couples in North America and Europe who are trying to conceive are infertile.
The fertility of a couple depends upon several factors in both the male and female partner. Among all cases of infertility, about 20 percent can be traced to male factors, 38 percent can be traced to female factors, 27 percent can be traced to factors in both the male and female partners, and 15 percent cannot be traced to obvious factors in either partner.
When infertility occurs, the male and female partners are evaluated to determine the cause and best treatment options. For couples where the woman is not ovulating regularly, one treatment option involves the female partner taking an oral medication, clomiphene citrate (Clomid® or Serophene®).
This topic will review the use of clomiphene in the treatment of female infertility. The evaluation of the infertile couple, as well as the causes and treatment of male infertility, is discussed separately. (See "Patient information: Evaluation of the infertile couple" and see "Patient information: Treatment of infertility in men").
OVULATION — To understand why and how clomiphene is used, it is necessary to understand normal ovulation. Normally, a woman's ovaries produce one egg every 24 to 35 days. Ovulation usually occurs about 12 to 14 days before the next menstrual period (show figure 1). A woman's best chances for becoming pregnant occurs around the day of ovulation and two to four days before ovulation. This would be approximately 10 to 14 days after the first day of the menstrual cycle (day 1 of the menstrual cycle is the first day of bleeding).
A complex balance of hormones is required to stimulate ovulation, changes in hormone levels can cause ovulation to occur irregularly or to temporarily stop. A woman who has absent or irregular ovulation is said to have anovulation or oligoovulation.
There are several types of anovulation, as defined by the World Health Organization (WHO). These types are organized by the woman's blood level of follicle stimulating hormone (FSH) and estrogen (estradiol). FSH is a hormone produced by the pituitary (a gland within the brain) and estrogen is a hormone produced by the ovaries. The levels of these hormones change throughout the menstrual cycle, as shown in figure 1 (show figure 1).
Women who are most likely to respond to clomiphene include those who do not have an excessively elevated level of FSH (demonstrating a decrease in the number of eggs within the ovaries) and who have uterine bleeding when treated with a progestin (WHO class 2) (show table 1). This includes women with polycystic ovary syndrome.
WHAT IS CLOMIPHENE? — Clomiphene is a hormone that acts on the hypothalamus, pituitary gland, and ovary to increase levels of FSH and luteinizing hormone (LH, which is also important in the process of ovulation). An increased level of these hormones improves the chances of growing an ovarian follicle that can then trigger ovulation. In women who ovulate irregularly, approximately 80 percent who take clomiphene will ovulate, and 30 to 40 percent of all women who take clomiphene become pregnant. These numbers apply to women who have taken three cycles of clomiphene.
Pretreatment evaluation — Before any infertility treatment begins, a woman and her partner should be evaluated to be sure that clomiphene is the best treatment. This evaluation may include a complete history and physical examination, a semen analysis (for men), blood testing, and other tests depending upon the individual situation. (See "Patient information: Evaluation of the infertile couple").
Dosing — Clomiphene is usually started on day three, four, or five of the menstrual cycle at a dose of 50 mg once daily for five days. The first day of bleeding is arbitrarily called cycle day one. If the woman does not have regular menstrual cycles (which is usually the situation), she may be given a course of progestin medication to induce a period.
The couple is advised to have intercourse every other day for one week, beginning around day 10 of the clomiphene cycle. The couple may plan intercourse by using an ovulation predictor kit, which uses a urine sample to predict when ovulation is about to occur by measuring the LH level; these are available without a prescription. Most fertility specialists recommend the use of the ovulation predictor kit.
Some clinicians measure the blood level of progesterone one week before the expected menstrual period to determine if ovulation occurred; blood testing may be preferred to ovulation predictor kits because it provides reliable evidence that ovulation occurred (rather than a prediction that ovulation might occur).
Some healthcare providers recommend transvaginal ultrasound monitoring for women undergoing clomiphene treatment. This involves inserting a thin probe into the vagina and using sound waves to view the size and number of developing follicles (which contain an egg).
Use of an ovulation predictor kit, blood testing, and/or ultrasound are not required for women using clomiphene, and testing does not improve pregnancy rates significantly. However, almost all fertility specialists recommend use of an ovulation predictor kit and blood testing to confirm ovulation. Some recommend ultrasound, but this requires more office visits and increases the cost of treatment.
If ovulation does not occur during the first month, the clomiphene dose may be increased. There is no benefit of increasing the clomiphene dose if ovulation occurs, even if pregnancy does not occur. Most pregnancies occur within the first six cycles of using clomiphene, and there is little benefit of continuing clomiphene treatment after six unsuccessful cycles.
Benefits — The benefit of clomiphene is that it is relatively inexpensive and can be used before other, more expensive testing (such as hysterosalpingogram or laparoscopy) or infertility treatments (eg, in vitro fertilization). It does not require monitoring with ultrasound or blood hormone levels, although monitoring may be recommended in some cases. Clomiphene improves the chances of becoming pregnant for most women who ovulate irregularly, and carries a low risk of dangerous side effects.
Risks — Risks of clomiphene therapy include a slightly increased rate of multiple pregnancies; approximately 6 percent of women who use clomiphene have twins, while less than 0.5 percent have triplets or greater. There is a small risk of the ovaries becoming enlarged, although severe enlargement (known as ovarian hyperstimulation syndrome) is rare.
Common side effects of clomiphene include hot flashes, abdominal bloating and pain, nausea and vomiting, and breast tenderness. Visual symptoms such as blurring, double vision, or seeing spots occur in 1 to 2 percent of women, and usually resolve when treatment stops. Mood swings, depression, and headaches can occur, but are rarely serious enough to cause the woman to stop treatment.
There is no increased risk of birth defects, miscarriage, or learning disability in children of women who took clomiphene. There is no increased risk of breast cancer or uterine cancer. There may be a slightly increased risk of ovarian cancer if more than 12 cycles of clomiphene are used.
IMPROVING CLOMIPHENE SUCCESS — Women who do not become pregnant after three cycles of clomiphene may need further testing before continuing with treatment. This may include a hysterosalpingogram, blood testing, and if not previously done, a semen analysis of the male partner. (See "Patient information: Evaluation of the infertile couple").
If these tests are normal and the couple would like to continue with clomiphene treatment, additional interventions may improve success. Depending upon the individual, this may include weight loss or gain, or use of additional medications such as metformin or dexamethasone.
Weight loss — Women who are overweight or obese and who ovulate infrequently often benefit from weight loss as a treatment for their infertility. Overweight is defined as having a body mass index (BMI) greater than 27 kg/m2. To calculate BMI, divide weight in pounds by height in inches; then divide that number by height in inches and multiply by 703. A BMI table may also be used (show table 2A-2B).
Weight loss is an inexpensive and low-risk treatment with no side effects that has been proven to improve the chances of ovulation and pregnancy in women who are overweight. In addition, having a normal or near-normal weight can reduce the risk of complications during pregnancy. Furthermore, achieving and maintaining a weight in the normal range has life-long health benefits. A combination of decreased calorie intake and exercise are recommended to achieve a 5 to 10 percent weight loss. (See "Patient information: Diet and health").
Weight gain — Women who are underweight (defined as a BMI less than 17 kg/m2), have eating disorders (eg, bulimia or anorexia), or participate in strenuous exercise regimens may ovulate irregularly or not at all. These women may be advised to gain weight to a goal BMI of at least 19 kg/m2 (show table 2A-2B), increase calorie intake, and modify exercise habits to include less strenuous activities.
Treatment with human chorionic gonadotropin — Some women who do not have an increase in their LH level midcycle do not ovulate (show figure 1), despite having a normally developed follicle (which contains an egg). These women often benefit from an injection of human chorionic gonadotropin (hCG), which acts like LH to trigger ovulation. Transvaginal ultrasound is used to determine when the follicle is ready, and the woman or her partner can be taught to give the injection at home. Ovulation occurs 36 to 44 hours after the injection, and intercourse can be timed accordingly.
Treatment for insulin resistance — Women with polycystic ovary syndrome who have absent or irregular ovulation are often insulin resistant. Insulin is a hormone produced by the pancreas that functions to break down food into energy. Insulin resistance causes the body to produce excessive amounts of insulin, which leads to elevated levels of other hormones that interfere with ovulation. Treatment of insulin resistance can reduce these hormones, increase the chances of normal ovulation, and improve the chances of responding to clomiphene.
Metformin — Metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®) is a medication that is used in the treatment of type 2 diabetes mellitus. It has also been used to treat insulin resistance in women with polycystic ovary syndrome and infertility if clomiphene treatment and/or weight loss is not successful. Some women who do not ovulate with clomiphene may ovulate with the combination of metformin plus clomiphene.
Metformin is thought to be safe to take while trying to become pregnant, but should be stopped once pregnancy is confirmed.
Glucocorticoid treatment — Women who are anovulatory WHO class 2 (show table 1) and have not ovulated in response to clomiphene treatment may benefit from treatment with clomiphene as well as a glucocorticoid (a type of steroid). Dexamethasone or prednisone are the glucorticoids most commonly used. One regimen is to use a glucocorticoid daily from the start of the treatment cycle through ovulation
CLOMIPHENE FAILURE — If a woman with anovulation does not become pregnant after three to six cycles of clomiphene, other infertility treatments may be considered. These include surgical treatments, ovulation induction with injectable medications and/or in vitro fertilization.
COSTS OF INFERTILITY TREATMENT — The costs of infertility treatments can be high depending upon what tests are required, the type and dose of medication(s) used, and the number of months that it takes to become pregnant. Insurance policies cover the costs of infertility treatment in some areas, although this varies by location and individual insurance policy. At this time, less than half of the states within the U.S. have laws requiring insurers to cover infertility treatment.
More information about a state's laws can be obtained by calling the state Insurance Commissioner's office. More information can also be found by visiting the website for the American Society of Reproductive Medicine (www.asrm.org/Patients/insur.html).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
Resolve: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Use of clomiphene citrate in women. Fertil Steril 2003; 80:1302.
2. Hughes, E, Collins, J, Vandekerckhove, P. Clomiphene citrate for unexplained subfertility in women (Cochrane review). Cochrane Database Syst Rev 2000; :CD000057.
3. Smith, YR, Randolph, JF Jr, Christman, GM, et al. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril 1998; 70:165.
4. Barbieri, RL. Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. Am J Obstet Gynecol 2000; 183:1412.
The fertility of a couple depends upon several factors in both the male and female partner. Among all cases of infertility, about 20 percent can be traced to male factors, 38 percent can be traced to female factors, 27 percent can be traced to factors in both the male and female partners, and 15 percent cannot be traced to obvious factors in either partner.
When infertility occurs, the male and female partners are evaluated to determine the cause and best treatment options. For couples where the woman is not ovulating regularly, one treatment option involves the female partner taking an oral medication, clomiphene citrate (Clomid® or Serophene®).
This topic will review the use of clomiphene in the treatment of female infertility. The evaluation of the infertile couple, as well as the causes and treatment of male infertility, is discussed separately. (See "Patient information: Evaluation of the infertile couple" and see "Patient information: Treatment of infertility in men").
OVULATION — To understand why and how clomiphene is used, it is necessary to understand normal ovulation. Normally, a woman's ovaries produce one egg every 24 to 35 days. Ovulation usually occurs about 12 to 14 days before the next menstrual period (show figure 1). A woman's best chances for becoming pregnant occurs around the day of ovulation and two to four days before ovulation. This would be approximately 10 to 14 days after the first day of the menstrual cycle (day 1 of the menstrual cycle is the first day of bleeding).
A complex balance of hormones is required to stimulate ovulation, changes in hormone levels can cause ovulation to occur irregularly or to temporarily stop. A woman who has absent or irregular ovulation is said to have anovulation or oligoovulation.
There are several types of anovulation, as defined by the World Health Organization (WHO). These types are organized by the woman's blood level of follicle stimulating hormone (FSH) and estrogen (estradiol). FSH is a hormone produced by the pituitary (a gland within the brain) and estrogen is a hormone produced by the ovaries. The levels of these hormones change throughout the menstrual cycle, as shown in figure 1 (show figure 1).
Women who are most likely to respond to clomiphene include those who do not have an excessively elevated level of FSH (demonstrating a decrease in the number of eggs within the ovaries) and who have uterine bleeding when treated with a progestin (WHO class 2) (show table 1). This includes women with polycystic ovary syndrome.
WHAT IS CLOMIPHENE? — Clomiphene is a hormone that acts on the hypothalamus, pituitary gland, and ovary to increase levels of FSH and luteinizing hormone (LH, which is also important in the process of ovulation). An increased level of these hormones improves the chances of growing an ovarian follicle that can then trigger ovulation. In women who ovulate irregularly, approximately 80 percent who take clomiphene will ovulate, and 30 to 40 percent of all women who take clomiphene become pregnant. These numbers apply to women who have taken three cycles of clomiphene.
Pretreatment evaluation — Before any infertility treatment begins, a woman and her partner should be evaluated to be sure that clomiphene is the best treatment. This evaluation may include a complete history and physical examination, a semen analysis (for men), blood testing, and other tests depending upon the individual situation. (See "Patient information: Evaluation of the infertile couple").
Dosing — Clomiphene is usually started on day three, four, or five of the menstrual cycle at a dose of 50 mg once daily for five days. The first day of bleeding is arbitrarily called cycle day one. If the woman does not have regular menstrual cycles (which is usually the situation), she may be given a course of progestin medication to induce a period.
The couple is advised to have intercourse every other day for one week, beginning around day 10 of the clomiphene cycle. The couple may plan intercourse by using an ovulation predictor kit, which uses a urine sample to predict when ovulation is about to occur by measuring the LH level; these are available without a prescription. Most fertility specialists recommend the use of the ovulation predictor kit.
Some clinicians measure the blood level of progesterone one week before the expected menstrual period to determine if ovulation occurred; blood testing may be preferred to ovulation predictor kits because it provides reliable evidence that ovulation occurred (rather than a prediction that ovulation might occur).
Some healthcare providers recommend transvaginal ultrasound monitoring for women undergoing clomiphene treatment. This involves inserting a thin probe into the vagina and using sound waves to view the size and number of developing follicles (which contain an egg).
Use of an ovulation predictor kit, blood testing, and/or ultrasound are not required for women using clomiphene, and testing does not improve pregnancy rates significantly. However, almost all fertility specialists recommend use of an ovulation predictor kit and blood testing to confirm ovulation. Some recommend ultrasound, but this requires more office visits and increases the cost of treatment.
If ovulation does not occur during the first month, the clomiphene dose may be increased. There is no benefit of increasing the clomiphene dose if ovulation occurs, even if pregnancy does not occur. Most pregnancies occur within the first six cycles of using clomiphene, and there is little benefit of continuing clomiphene treatment after six unsuccessful cycles.
Benefits — The benefit of clomiphene is that it is relatively inexpensive and can be used before other, more expensive testing (such as hysterosalpingogram or laparoscopy) or infertility treatments (eg, in vitro fertilization). It does not require monitoring with ultrasound or blood hormone levels, although monitoring may be recommended in some cases. Clomiphene improves the chances of becoming pregnant for most women who ovulate irregularly, and carries a low risk of dangerous side effects.
Risks — Risks of clomiphene therapy include a slightly increased rate of multiple pregnancies; approximately 6 percent of women who use clomiphene have twins, while less than 0.5 percent have triplets or greater. There is a small risk of the ovaries becoming enlarged, although severe enlargement (known as ovarian hyperstimulation syndrome) is rare.
Common side effects of clomiphene include hot flashes, abdominal bloating and pain, nausea and vomiting, and breast tenderness. Visual symptoms such as blurring, double vision, or seeing spots occur in 1 to 2 percent of women, and usually resolve when treatment stops. Mood swings, depression, and headaches can occur, but are rarely serious enough to cause the woman to stop treatment.
There is no increased risk of birth defects, miscarriage, or learning disability in children of women who took clomiphene. There is no increased risk of breast cancer or uterine cancer. There may be a slightly increased risk of ovarian cancer if more than 12 cycles of clomiphene are used.
IMPROVING CLOMIPHENE SUCCESS — Women who do not become pregnant after three cycles of clomiphene may need further testing before continuing with treatment. This may include a hysterosalpingogram, blood testing, and if not previously done, a semen analysis of the male partner. (See "Patient information: Evaluation of the infertile couple").
If these tests are normal and the couple would like to continue with clomiphene treatment, additional interventions may improve success. Depending upon the individual, this may include weight loss or gain, or use of additional medications such as metformin or dexamethasone.
Weight loss — Women who are overweight or obese and who ovulate infrequently often benefit from weight loss as a treatment for their infertility. Overweight is defined as having a body mass index (BMI) greater than 27 kg/m2. To calculate BMI, divide weight in pounds by height in inches; then divide that number by height in inches and multiply by 703. A BMI table may also be used (show table 2A-2B).
Weight loss is an inexpensive and low-risk treatment with no side effects that has been proven to improve the chances of ovulation and pregnancy in women who are overweight. In addition, having a normal or near-normal weight can reduce the risk of complications during pregnancy. Furthermore, achieving and maintaining a weight in the normal range has life-long health benefits. A combination of decreased calorie intake and exercise are recommended to achieve a 5 to 10 percent weight loss. (See "Patient information: Diet and health").
Weight gain — Women who are underweight (defined as a BMI less than 17 kg/m2), have eating disorders (eg, bulimia or anorexia), or participate in strenuous exercise regimens may ovulate irregularly or not at all. These women may be advised to gain weight to a goal BMI of at least 19 kg/m2 (show table 2A-2B), increase calorie intake, and modify exercise habits to include less strenuous activities.
Treatment with human chorionic gonadotropin — Some women who do not have an increase in their LH level midcycle do not ovulate (show figure 1), despite having a normally developed follicle (which contains an egg). These women often benefit from an injection of human chorionic gonadotropin (hCG), which acts like LH to trigger ovulation. Transvaginal ultrasound is used to determine when the follicle is ready, and the woman or her partner can be taught to give the injection at home. Ovulation occurs 36 to 44 hours after the injection, and intercourse can be timed accordingly.
Treatment for insulin resistance — Women with polycystic ovary syndrome who have absent or irregular ovulation are often insulin resistant. Insulin is a hormone produced by the pancreas that functions to break down food into energy. Insulin resistance causes the body to produce excessive amounts of insulin, which leads to elevated levels of other hormones that interfere with ovulation. Treatment of insulin resistance can reduce these hormones, increase the chances of normal ovulation, and improve the chances of responding to clomiphene.
Metformin — Metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®) is a medication that is used in the treatment of type 2 diabetes mellitus. It has also been used to treat insulin resistance in women with polycystic ovary syndrome and infertility if clomiphene treatment and/or weight loss is not successful. Some women who do not ovulate with clomiphene may ovulate with the combination of metformin plus clomiphene.
Metformin is thought to be safe to take while trying to become pregnant, but should be stopped once pregnancy is confirmed.
Glucocorticoid treatment — Women who are anovulatory WHO class 2 (show table 1) and have not ovulated in response to clomiphene treatment may benefit from treatment with clomiphene as well as a glucocorticoid (a type of steroid). Dexamethasone or prednisone are the glucorticoids most commonly used. One regimen is to use a glucocorticoid daily from the start of the treatment cycle through ovulation
CLOMIPHENE FAILURE — If a woman with anovulation does not become pregnant after three to six cycles of clomiphene, other infertility treatments may be considered. These include surgical treatments, ovulation induction with injectable medications and/or in vitro fertilization.
COSTS OF INFERTILITY TREATMENT — The costs of infertility treatments can be high depending upon what tests are required, the type and dose of medication(s) used, and the number of months that it takes to become pregnant. Insurance policies cover the costs of infertility treatment in some areas, although this varies by location and individual insurance policy. At this time, less than half of the states within the U.S. have laws requiring insurers to cover infertility treatment.
More information about a state's laws can be obtained by calling the state Insurance Commissioner's office. More information can also be found by visiting the website for the American Society of Reproductive Medicine (www.asrm.org/Patients/insur.html).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
Resolve: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Use of clomiphene citrate in women. Fertil Steril 2003; 80:1302.
2. Hughes, E, Collins, J, Vandekerckhove, P. Clomiphene citrate for unexplained subfertility in women (Cochrane review). Cochrane Database Syst Rev 2000; :CD000057.
3. Smith, YR, Randolph, JF Jr, Christman, GM, et al. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril 1998; 70:165.
4. Barbieri, RL. Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. Am J Obstet Gynecol 2000; 183:1412.
Evaluation of the infertile couple
INTRODUCTION — Infertility is defined as the inability of a couple to become pregnant after one year of unprotected intercourse. Infertility is a common condition: in any given year, about 15 percent of the couples in the United States who are trying to conceive are not able to do so.
The ability of a couple to become pregnant depends on several factors in both the male and female partners. Among all cases of infertility, about 20 percent can be traced to male factors, 40 percent can be traced to female factors, and 30 percent can be traced to factors in both the male and female partners. In about 15 percent of couples, the etiology for infertility cannot be traced to specific factors in either partner.
Because fertility involves a complex interaction of male and female factors, healthcare providers routinely involve both partners in the evaluation.
EVALUATION OF MEN — Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes. Therefore, a variety of different conditions can lead to infertility. The evaluation of male infertility may point to an underlying cause, which can guide treatment. A healthcare provider usually begins with a medical history, physical examination, and a semen test. Other tests may be needed in some men.
History — A man's past health and medical history are important in the process of evaluation. A healthcare provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility testing.
Physical examination — A physical examination usually includes measurement of height and weight, assessment of body fat and muscle distribution, inspection of the skin and hair pattern, and visual examination of the genitals and breasts (show figure 1).
Special attention is given to features of testosterone deficiency, which may include loss of facial and body hair and decrease in the size of the testis.
Other conditions that can affect fertility include: Varicocele, a varicose vein of the testicle Absent vas deferens or thickening of the epididymis (show figure 1)
Semen analysis — A semen analysis (sperm count) is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen, and the number, motility, and shape of sperm.
A man should avoid sex and masturbation for two to seven days before providing the semen sample. Ideally, a sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the lab within one hour of collection.
If the initial semen analysis is abnormal, the clinician will often request an additional sample; this is best done one to two weeks later.
Blood tests — Blood tests provide information about hormones that play a role in male fertility. If sperm concentration is low or the clinician suspects a hormonal problem, blood tests to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone) may be ordered.
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be needed to check for absent or abnormal regions of the male chromosomes (Y chromosome).
Although infertility treatments may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to inform a couple about the possibility of parent-to-child transmission and possible impact of the abnormality.
Other tests — If obstruction of the reproductive tract (epididymis or vas deferens) is suspected, a transrectal ultrasound test may be ordered. This test can identify areas of blockage in the male reproductive tract.
A post-ejaculation urine sample is needed if retrograde ejaculation (movement of semen into the bladder) is suspected.
A testicular biopsy (collection of a small tissue sample) can be done by surgically opening the testis or by fine-needle aspiration (inserting a small needle into the testis and withdrawing a sample of tissue). An open biopsy is usually done in an operating room with general anesthesia while a fine-needle aspiration may be done with local anesthesia in an office setting. The biopsy allows the physician to examine the microscopic structure of the testes and determine if sperm are present.
EVALUATION OF WOMEN — Although a variety of tests are available for evaluating female infertility, it may not be necessary to have all of these tests. Healthcare providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — A woman's past health and medical history may provide some clues about the cause of infertility. The healthcare provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications used; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility evaluations.
Physical examination — A physical examination usually includes a general examination, with special attention to any signs of hormone deficiency or signs of other conditions that might impair fertility. The provider will also perform a pelvic examination, which can identify abnormalities of the reproductive tract and signs of low hormone levels (show figure 2).
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; in women, key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
Tests to evaluate ovulation — Ovulation (the release of an egg from an ovary) is essential for fertility. Abnormalities of ovulation can often be determined from a woman's menstrual history or hormone levels such as the pre-ovulatory LH surge or luteal phase progesterone (show figure 3).
Menstrual history — Amenorrhea (absent menstrual periods) usually signals an absence of ovulation, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular ovulation; although oligomenorrhea does not make pregnancy impossible, it can interfere with the ability to become pregnant.
Basal body temperature — Monitoring of basal body temperature (measured before getting out of bed in the morning) was previously recommended to determine if ovulation occurred. A woman's temperature usually rises by 0.5ºF to 1.0ºF after ovulation. However, basal body temperature patterns can be difficult to interpret and are not generally recommended in the evaluation of infertility.
Hormone levels — Levels of luteinizing hormone (LH) rise abruptly approximately 38 hours before ovulation. This hormone surge can be detected using an over-the-counter urinary test kit. However, this kit fails to detect the hormone surge about 15 percent of the time. Therefore, a clinician may recommend a blood test to confirm ovulation.
Blood levels of the hormone progesterone are a more accurate indicator of ovulation. Normally, levels of progesterone rise after ovulation. Progesterone tests are usually performed 18 to 24 days after the first day of a menstrual period.
Tests to evaluate the uterus and fallopian tubes — Uterine abnormalities that can contribute to infertility include congenital structural abnormalities, such as a uterine septum (a band of tissue that makes the uterine cavity small) (show figure 4); abnormalities linked to exposure to diethylstilbestrol (DES) (a hormone used in the past to prevent miscarriage), which can cause a T-shaped uterus (show figure 5); fibroids; polyps; and structural abnormalities that can result from gynecologic procedures.
Scarring and obstruction of the fallopian tubes can occur as a result of pelvic inflammatory disease, endometriosis or pelvic adhesions (scar tissue) from abdominal infection or surgery.
Hysterosalpingography — Hysterosalpingogram (HSG) is used to help identify structural abnormalities of the uterus and fallopian tubes. It involves inserting a small catheter through the cervix and into the uterus. A liquid dye is injected through the catheter, which fills the uterus and fallopian tubes. An x-ray is taken after the dye is injected, which shows the outline of the uterus and tubes (show radiograph 1). An abnormally shaped uterus or blocked fallopian tube would be visible on the x-ray (show radiograph 2).
The test is done while the woman is awake and lying on an x-ray table. Most women experience moderate to severe pelvic cramps when the dye is injected, but this usually improves after five to 10 minutes. The test is usually performed five to seven days after the menstrual period (before ovulation has occurred).
Hysteroscopy — In a hysteroscopy, a small tube with a camera is inserted through the cervix and into the uterus. Air or fluid is injected to expand the uterus and to allow the physician to see inside the uterus.
A hysteroscopy is usually performed in women who are thought to have an abnormal uterus, based upon hysterosalpingogram or ultrasound; several structural abnormalities can be surgically treated during hysteroscopy. Hysteroscopy is performed as a day (outpatient) surgery. Sedation with regional anesthesia (local, epidural, or spinal anesthesia) or general anesthesia is used during the procedure.
Pelvic ultrasound — In a transvaginal ultrasound, a small ultrasound probe is inserted into the vagina; this provides a clearer image of the uterus and ovaries than ultrasound that is performed through the abdomen. It does not require that the patient is sedated or anesthetized, and has few to no risks. It is used to measure the size and shape of the uterus and ovaries, and to determine if there are structural abnormalities (such as fibroids or ovarian cysts). If abnormalities are seen, further testing may be needed.
Laparoscopy — During laparoscopy, a thin, lighted tube is inserted through a small incision in the abdomen, allowing the physician to view the uterus, ovaries, and fallopian tubes. Laparoscopy is performed as a day surgery procedure, and requires that the patient receive general anesthesia.
Laparoscopy can detect damage and obstruction of the fallopian tubes, endometriosis, and other abnormalities of the pelvic structures. It is the best test for diagnosis of endometriosis or pelvic adhesions (scarring). Furthermore, endometriosis can be treated during laparoscopy, which can help to improve pregnancy rates in women with infertility who have endometriosis. However, laparoscopy is not routinely done during an evaluation of infertility.
Genetic tests — Genetic testing may be recommended if there is a suspicion that genetic or chromosomal abnormalities are contributing to infertility. These tests usually require a small blood sample, which is sent to a laboratory for evaluation.
Although assisted reproductive techniques may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to educate a couple about the possibility of parent to child transmission, possible impact of the abnormality, and treatments available to prevent parent-to-child transmission.
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — The process of trying to become pregnant and the inability to do so can lead to a variety of emotions, including anxiety, depression, anger, shame, and guilt. In one study, 40 percent of infertility patients suffered with some type of psychiatric disorder; the most common diagnosis was an anxiety disorder (23 percent), followed by major depressive disorder (17 percent) [1].
Both men and women can suffer from these problems, which can further hinder a couple's ability to become pregnant. Psychological distress is associated with infertility treatment failure and interventions to relieve stress are associated with increased pregnancy rates.
The best approach for treatment of psychological distress related to infertility treatment has not been determined. However, some experts suggest relaxation techniques, stress-management, coping skills training, and group support. Evaluation by a psychiatrist may be needed for some persons with significant symptoms of anxiety or depression.
TREATMENT — There are a number of options for treatment of both male and female infertility. Separate topic reviews are available. (See "Patient information: Treatment of infertility in men" and see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
RESOLVE: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.org)
The Hormone Foundation
(www.hormone.org/public/other.cfm, available in English and Spanish)
[2-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chen, TH, Chang, SP, Tsai, CF, Juang, KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod 2004; 19:2313.
2. De Kretser, DM. Male infertility. Lancet 1997; 349:787.
3. De Kretser, DM, Baker, HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
4. Gray, RH. Epidemiology of infertility. Curr Opin Obstet Gynecol 1990; 2:154.
5. Guzick, DS, Grefenstette, I, Baffone, K, et al. Infertility evaluation in fertile women: A model for assessing the efficacy of infertility testing. Hum Reprod 1994; 9:2306.
6. Templeton, A, Fraser, C, Thompson, B. Infertility--epidemiology and referral practice. Hum Reprod 1991; 6:1391.
The ability of a couple to become pregnant depends on several factors in both the male and female partners. Among all cases of infertility, about 20 percent can be traced to male factors, 40 percent can be traced to female factors, and 30 percent can be traced to factors in both the male and female partners. In about 15 percent of couples, the etiology for infertility cannot be traced to specific factors in either partner.
Because fertility involves a complex interaction of male and female factors, healthcare providers routinely involve both partners in the evaluation.
EVALUATION OF MEN — Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes. Therefore, a variety of different conditions can lead to infertility. The evaluation of male infertility may point to an underlying cause, which can guide treatment. A healthcare provider usually begins with a medical history, physical examination, and a semen test. Other tests may be needed in some men.
History — A man's past health and medical history are important in the process of evaluation. A healthcare provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility testing.
Physical examination — A physical examination usually includes measurement of height and weight, assessment of body fat and muscle distribution, inspection of the skin and hair pattern, and visual examination of the genitals and breasts (show figure 1).
Special attention is given to features of testosterone deficiency, which may include loss of facial and body hair and decrease in the size of the testis.
Other conditions that can affect fertility include: Varicocele, a varicose vein of the testicle Absent vas deferens or thickening of the epididymis (show figure 1)
Semen analysis — A semen analysis (sperm count) is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen, and the number, motility, and shape of sperm.
A man should avoid sex and masturbation for two to seven days before providing the semen sample. Ideally, a sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the lab within one hour of collection.
If the initial semen analysis is abnormal, the clinician will often request an additional sample; this is best done one to two weeks later.
Blood tests — Blood tests provide information about hormones that play a role in male fertility. If sperm concentration is low or the clinician suspects a hormonal problem, blood tests to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone) may be ordered.
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be needed to check for absent or abnormal regions of the male chromosomes (Y chromosome).
Although infertility treatments may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to inform a couple about the possibility of parent-to-child transmission and possible impact of the abnormality.
Other tests — If obstruction of the reproductive tract (epididymis or vas deferens) is suspected, a transrectal ultrasound test may be ordered. This test can identify areas of blockage in the male reproductive tract.
A post-ejaculation urine sample is needed if retrograde ejaculation (movement of semen into the bladder) is suspected.
A testicular biopsy (collection of a small tissue sample) can be done by surgically opening the testis or by fine-needle aspiration (inserting a small needle into the testis and withdrawing a sample of tissue). An open biopsy is usually done in an operating room with general anesthesia while a fine-needle aspiration may be done with local anesthesia in an office setting. The biopsy allows the physician to examine the microscopic structure of the testes and determine if sperm are present.
EVALUATION OF WOMEN — Although a variety of tests are available for evaluating female infertility, it may not be necessary to have all of these tests. Healthcare providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — A woman's past health and medical history may provide some clues about the cause of infertility. The healthcare provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications used; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility evaluations.
Physical examination — A physical examination usually includes a general examination, with special attention to any signs of hormone deficiency or signs of other conditions that might impair fertility. The provider will also perform a pelvic examination, which can identify abnormalities of the reproductive tract and signs of low hormone levels (show figure 2).
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; in women, key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
Tests to evaluate ovulation — Ovulation (the release of an egg from an ovary) is essential for fertility. Abnormalities of ovulation can often be determined from a woman's menstrual history or hormone levels such as the pre-ovulatory LH surge or luteal phase progesterone (show figure 3).
Menstrual history — Amenorrhea (absent menstrual periods) usually signals an absence of ovulation, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular ovulation; although oligomenorrhea does not make pregnancy impossible, it can interfere with the ability to become pregnant.
Basal body temperature — Monitoring of basal body temperature (measured before getting out of bed in the morning) was previously recommended to determine if ovulation occurred. A woman's temperature usually rises by 0.5ºF to 1.0ºF after ovulation. However, basal body temperature patterns can be difficult to interpret and are not generally recommended in the evaluation of infertility.
Hormone levels — Levels of luteinizing hormone (LH) rise abruptly approximately 38 hours before ovulation. This hormone surge can be detected using an over-the-counter urinary test kit. However, this kit fails to detect the hormone surge about 15 percent of the time. Therefore, a clinician may recommend a blood test to confirm ovulation.
Blood levels of the hormone progesterone are a more accurate indicator of ovulation. Normally, levels of progesterone rise after ovulation. Progesterone tests are usually performed 18 to 24 days after the first day of a menstrual period.
Tests to evaluate the uterus and fallopian tubes — Uterine abnormalities that can contribute to infertility include congenital structural abnormalities, such as a uterine septum (a band of tissue that makes the uterine cavity small) (show figure 4); abnormalities linked to exposure to diethylstilbestrol (DES) (a hormone used in the past to prevent miscarriage), which can cause a T-shaped uterus (show figure 5); fibroids; polyps; and structural abnormalities that can result from gynecologic procedures.
Scarring and obstruction of the fallopian tubes can occur as a result of pelvic inflammatory disease, endometriosis or pelvic adhesions (scar tissue) from abdominal infection or surgery.
Hysterosalpingography — Hysterosalpingogram (HSG) is used to help identify structural abnormalities of the uterus and fallopian tubes. It involves inserting a small catheter through the cervix and into the uterus. A liquid dye is injected through the catheter, which fills the uterus and fallopian tubes. An x-ray is taken after the dye is injected, which shows the outline of the uterus and tubes (show radiograph 1). An abnormally shaped uterus or blocked fallopian tube would be visible on the x-ray (show radiograph 2).
The test is done while the woman is awake and lying on an x-ray table. Most women experience moderate to severe pelvic cramps when the dye is injected, but this usually improves after five to 10 minutes. The test is usually performed five to seven days after the menstrual period (before ovulation has occurred).
Hysteroscopy — In a hysteroscopy, a small tube with a camera is inserted through the cervix and into the uterus. Air or fluid is injected to expand the uterus and to allow the physician to see inside the uterus.
A hysteroscopy is usually performed in women who are thought to have an abnormal uterus, based upon hysterosalpingogram or ultrasound; several structural abnormalities can be surgically treated during hysteroscopy. Hysteroscopy is performed as a day (outpatient) surgery. Sedation with regional anesthesia (local, epidural, or spinal anesthesia) or general anesthesia is used during the procedure.
Pelvic ultrasound — In a transvaginal ultrasound, a small ultrasound probe is inserted into the vagina; this provides a clearer image of the uterus and ovaries than ultrasound that is performed through the abdomen. It does not require that the patient is sedated or anesthetized, and has few to no risks. It is used to measure the size and shape of the uterus and ovaries, and to determine if there are structural abnormalities (such as fibroids or ovarian cysts). If abnormalities are seen, further testing may be needed.
Laparoscopy — During laparoscopy, a thin, lighted tube is inserted through a small incision in the abdomen, allowing the physician to view the uterus, ovaries, and fallopian tubes. Laparoscopy is performed as a day surgery procedure, and requires that the patient receive general anesthesia.
Laparoscopy can detect damage and obstruction of the fallopian tubes, endometriosis, and other abnormalities of the pelvic structures. It is the best test for diagnosis of endometriosis or pelvic adhesions (scarring). Furthermore, endometriosis can be treated during laparoscopy, which can help to improve pregnancy rates in women with infertility who have endometriosis. However, laparoscopy is not routinely done during an evaluation of infertility.
Genetic tests — Genetic testing may be recommended if there is a suspicion that genetic or chromosomal abnormalities are contributing to infertility. These tests usually require a small blood sample, which is sent to a laboratory for evaluation.
Although assisted reproductive techniques may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to educate a couple about the possibility of parent to child transmission, possible impact of the abnormality, and treatments available to prevent parent-to-child transmission.
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — The process of trying to become pregnant and the inability to do so can lead to a variety of emotions, including anxiety, depression, anger, shame, and guilt. In one study, 40 percent of infertility patients suffered with some type of psychiatric disorder; the most common diagnosis was an anxiety disorder (23 percent), followed by major depressive disorder (17 percent) [1].
Both men and women can suffer from these problems, which can further hinder a couple's ability to become pregnant. Psychological distress is associated with infertility treatment failure and interventions to relieve stress are associated with increased pregnancy rates.
The best approach for treatment of psychological distress related to infertility treatment has not been determined. However, some experts suggest relaxation techniques, stress-management, coping skills training, and group support. Evaluation by a psychiatrist may be needed for some persons with significant symptoms of anxiety or depression.
TREATMENT — There are a number of options for treatment of both male and female infertility. Separate topic reviews are available. (See "Patient information: Treatment of infertility in men" and see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
RESOLVE: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.org)
The Hormone Foundation
(www.hormone.org/public/other.cfm, available in English and Spanish)
[2-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chen, TH, Chang, SP, Tsai, CF, Juang, KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod 2004; 19:2313.
2. De Kretser, DM. Male infertility. Lancet 1997; 349:787.
3. De Kretser, DM, Baker, HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
4. Gray, RH. Epidemiology of infertility. Curr Opin Obstet Gynecol 1990; 2:154.
5. Guzick, DS, Grefenstette, I, Baffone, K, et al. Infertility evaluation in fertile women: A model for assessing the efficacy of infertility testing. Hum Reprod 1994; 9:2306.
6. Templeton, A, Fraser, C, Thompson, B. Infertility--epidemiology and referral practice. Hum Reprod 1991; 6:1391.
Evaluation of the infertile couple
INTRODUCTION — Infertility is defined as the inability of a couple to become pregnant after one year of unprotected intercourse. Infertility is a common condition: in any given year, about 15 percent of the couples in the United States who are trying to conceive are not able to do so.
The ability of a couple to become pregnant depends on several factors in both the male and female partners. Among all cases of infertility, about 20 percent can be traced to male factors, 40 percent can be traced to female factors, and 30 percent can be traced to factors in both the male and female partners. In about 15 percent of couples, the etiology for infertility cannot be traced to specific factors in either partner.
Because fertility involves a complex interaction of male and female factors, healthcare providers routinely involve both partners in the evaluation.
EVALUATION OF MEN — Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes. Therefore, a variety of different conditions can lead to infertility. The evaluation of male infertility may point to an underlying cause, which can guide treatment. A healthcare provider usually begins with a medical history, physical examination, and a semen test. Other tests may be needed in some men.
History — A man's past health and medical history are important in the process of evaluation. A healthcare provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility testing.
Physical examination — A physical examination usually includes measurement of height and weight, assessment of body fat and muscle distribution, inspection of the skin and hair pattern, and visual examination of the genitals and breasts (show figure 1).
Special attention is given to features of testosterone deficiency, which may include loss of facial and body hair and decrease in the size of the testis.
Other conditions that can affect fertility include: Varicocele, a varicose vein of the testicle Absent vas deferens or thickening of the epididymis (show figure 1)
Semen analysis — A semen analysis (sperm count) is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen, and the number, motility, and shape of sperm.
A man should avoid sex and masturbation for two to seven days before providing the semen sample. Ideally, a sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the lab within one hour of collection.
If the initial semen analysis is abnormal, the clinician will often request an additional sample; this is best done one to two weeks later.
Blood tests — Blood tests provide information about hormones that play a role in male fertility. If sperm concentration is low or the clinician suspects a hormonal problem, blood tests to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone) may be ordered.
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be needed to check for absent or abnormal regions of the male chromosomes (Y chromosome).
Although infertility treatments may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to inform a couple about the possibility of parent-to-child transmission and possible impact of the abnormality.
Other tests — If obstruction of the reproductive tract (epididymis or vas deferens) is suspected, a transrectal ultrasound test may be ordered. This test can identify areas of blockage in the male reproductive tract.
A post-ejaculation urine sample is needed if retrograde ejaculation (movement of semen into the bladder) is suspected.
A testicular biopsy (collection of a small tissue sample) can be done by surgically opening the testis or by fine-needle aspiration (inserting a small needle into the testis and withdrawing a sample of tissue). An open biopsy is usually done in an operating room with general anesthesia while a fine-needle aspiration may be done with local anesthesia in an office setting. The biopsy allows the physician to examine the microscopic structure of the testes and determine if sperm are present.
EVALUATION OF WOMEN — Although a variety of tests are available for evaluating female infertility, it may not be necessary to have all of these tests. Healthcare providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — A woman's past health and medical history may provide some clues about the cause of infertility. The healthcare provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications used; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility evaluations.
Physical examination — A physical examination usually includes a general examination, with special attention to any signs of hormone deficiency or signs of other conditions that might impair fertility. The provider will also perform a pelvic examination, which can identify abnormalities of the reproductive tract and signs of low hormone levels (show figure 2).
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; in women, key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
Tests to evaluate ovulation — Ovulation (the release of an egg from an ovary) is essential for fertility. Abnormalities of ovulation can often be determined from a woman's menstrual history or hormone levels such as the pre-ovulatory LH surge or luteal phase progesterone (show figure 3).
Menstrual history — Amenorrhea (absent menstrual periods) usually signals an absence of ovulation, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular ovulation; although oligomenorrhea does not make pregnancy impossible, it can interfere with the ability to become pregnant.
Basal body temperature — Monitoring of basal body temperature (measured before getting out of bed in the morning) was previously recommended to determine if ovulation occurred. A woman's temperature usually rises by 0.5ºF to 1.0ºF after ovulation. However, basal body temperature patterns can be difficult to interpret and are not generally recommended in the evaluation of infertility.
Hormone levels — Levels of luteinizing hormone (LH) rise abruptly approximately 38 hours before ovulation. This hormone surge can be detected using an over-the-counter urinary test kit. However, this kit fails to detect the hormone surge about 15 percent of the time. Therefore, a clinician may recommend a blood test to confirm ovulation.
Blood levels of the hormone progesterone are a more accurate indicator of ovulation. Normally, levels of progesterone rise after ovulation. Progesterone tests are usually performed 18 to 24 days after the first day of a menstrual period.
Tests to evaluate the uterus and fallopian tubes — Uterine abnormalities that can contribute to infertility include congenital structural abnormalities, such as a uterine septum (a band of tissue that makes the uterine cavity small) (show figure 4); abnormalities linked to exposure to diethylstilbestrol (DES) (a hormone used in the past to prevent miscarriage), which can cause a T-shaped uterus (show figure 5); fibroids; polyps; and structural abnormalities that can result from gynecologic procedures.
Scarring and obstruction of the fallopian tubes can occur as a result of pelvic inflammatory disease, endometriosis or pelvic adhesions (scar tissue) from abdominal infection or surgery.
Hysterosalpingography — Hysterosalpingogram (HSG) is used to help identify structural abnormalities of the uterus and fallopian tubes. It involves inserting a small catheter through the cervix and into the uterus. A liquid dye is injected through the catheter, which fills the uterus and fallopian tubes. An x-ray is taken after the dye is injected, which shows the outline of the uterus and tubes (show radiograph 1). An abnormally shaped uterus or blocked fallopian tube would be visible on the x-ray (show radiograph 2).
The test is done while the woman is awake and lying on an x-ray table. Most women experience moderate to severe pelvic cramps when the dye is injected, but this usually improves after five to 10 minutes. The test is usually performed five to seven days after the menstrual period (before ovulation has occurred).
Hysteroscopy — In a hysteroscopy, a small tube with a camera is inserted through the cervix and into the uterus. Air or fluid is injected to expand the uterus and to allow the physician to see inside the uterus.
A hysteroscopy is usually performed in women who are thought to have an abnormal uterus, based upon hysterosalpingogram or ultrasound; several structural abnormalities can be surgically treated during hysteroscopy. Hysteroscopy is performed as a day (outpatient) surgery. Sedation with regional anesthesia (local, epidural, or spinal anesthesia) or general anesthesia is used during the procedure.
Pelvic ultrasound — In a transvaginal ultrasound, a small ultrasound probe is inserted into the vagina; this provides a clearer image of the uterus and ovaries than ultrasound that is performed through the abdomen. It does not require that the patient is sedated or anesthetized, and has few to no risks. It is used to measure the size and shape of the uterus and ovaries, and to determine if there are structural abnormalities (such as fibroids or ovarian cysts). If abnormalities are seen, further testing may be needed.
Laparoscopy — During laparoscopy, a thin, lighted tube is inserted through a small incision in the abdomen, allowing the physician to view the uterus, ovaries, and fallopian tubes. Laparoscopy is performed as a day surgery procedure, and requires that the patient receive general anesthesia.
Laparoscopy can detect damage and obstruction of the fallopian tubes, endometriosis, and other abnormalities of the pelvic structures. It is the best test for diagnosis of endometriosis or pelvic adhesions (scarring). Furthermore, endometriosis can be treated during laparoscopy, which can help to improve pregnancy rates in women with infertility who have endometriosis. However, laparoscopy is not routinely done during an evaluation of infertility.
Genetic tests — Genetic testing may be recommended if there is a suspicion that genetic or chromosomal abnormalities are contributing to infertility. These tests usually require a small blood sample, which is sent to a laboratory for evaluation.
Although assisted reproductive techniques may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to educate a couple about the possibility of parent to child transmission, possible impact of the abnormality, and treatments available to prevent parent-to-child transmission.
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — The process of trying to become pregnant and the inability to do so can lead to a variety of emotions, including anxiety, depression, anger, shame, and guilt. In one study, 40 percent of infertility patients suffered with some type of psychiatric disorder; the most common diagnosis was an anxiety disorder (23 percent), followed by major depressive disorder (17 percent) [1].
Both men and women can suffer from these problems, which can further hinder a couple's ability to become pregnant. Psychological distress is associated with infertility treatment failure and interventions to relieve stress are associated with increased pregnancy rates.
The best approach for treatment of psychological distress related to infertility treatment has not been determined. However, some experts suggest relaxation techniques, stress-management, coping skills training, and group support. Evaluation by a psychiatrist may be needed for some persons with significant symptoms of anxiety or depression.
TREATMENT — There are a number of options for treatment of both male and female infertility. Separate topic reviews are available. (See "Patient information: Treatment of infertility in men" and see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
RESOLVE: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.org)
The Hormone Foundation
(www.hormone.org/public/other.cfm, available in English and Spanish)
[2-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chen, TH, Chang, SP, Tsai, CF, Juang, KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod 2004; 19:2313.
2. De Kretser, DM. Male infertility. Lancet 1997; 349:787.
3. De Kretser, DM, Baker, HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
4. Gray, RH. Epidemiology of infertility. Curr Opin Obstet Gynecol 1990; 2:154.
5. Guzick, DS, Grefenstette, I, Baffone, K, et al. Infertility evaluation in fertile women: A model for assessing the efficacy of infertility testing. Hum Reprod 1994; 9:2306.
6. Templeton, A, Fraser, C, Thompson, B. Infertility--epidemiology and referral practice. Hum Reprod 1991; 6:1391.
The ability of a couple to become pregnant depends on several factors in both the male and female partners. Among all cases of infertility, about 20 percent can be traced to male factors, 40 percent can be traced to female factors, and 30 percent can be traced to factors in both the male and female partners. In about 15 percent of couples, the etiology for infertility cannot be traced to specific factors in either partner.
Because fertility involves a complex interaction of male and female factors, healthcare providers routinely involve both partners in the evaluation.
EVALUATION OF MEN — Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes. Therefore, a variety of different conditions can lead to infertility. The evaluation of male infertility may point to an underlying cause, which can guide treatment. A healthcare provider usually begins with a medical history, physical examination, and a semen test. Other tests may be needed in some men.
History — A man's past health and medical history are important in the process of evaluation. A healthcare provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility testing.
Physical examination — A physical examination usually includes measurement of height and weight, assessment of body fat and muscle distribution, inspection of the skin and hair pattern, and visual examination of the genitals and breasts (show figure 1).
Special attention is given to features of testosterone deficiency, which may include loss of facial and body hair and decrease in the size of the testis.
Other conditions that can affect fertility include: Varicocele, a varicose vein of the testicle Absent vas deferens or thickening of the epididymis (show figure 1)
Semen analysis — A semen analysis (sperm count) is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen, and the number, motility, and shape of sperm.
A man should avoid sex and masturbation for two to seven days before providing the semen sample. Ideally, a sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the lab within one hour of collection.
If the initial semen analysis is abnormal, the clinician will often request an additional sample; this is best done one to two weeks later.
Blood tests — Blood tests provide information about hormones that play a role in male fertility. If sperm concentration is low or the clinician suspects a hormonal problem, blood tests to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone) may be ordered.
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be needed to check for absent or abnormal regions of the male chromosomes (Y chromosome).
Although infertility treatments may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to inform a couple about the possibility of parent-to-child transmission and possible impact of the abnormality.
Other tests — If obstruction of the reproductive tract (epididymis or vas deferens) is suspected, a transrectal ultrasound test may be ordered. This test can identify areas of blockage in the male reproductive tract.
A post-ejaculation urine sample is needed if retrograde ejaculation (movement of semen into the bladder) is suspected.
A testicular biopsy (collection of a small tissue sample) can be done by surgically opening the testis or by fine-needle aspiration (inserting a small needle into the testis and withdrawing a sample of tissue). An open biopsy is usually done in an operating room with general anesthesia while a fine-needle aspiration may be done with local anesthesia in an office setting. The biopsy allows the physician to examine the microscopic structure of the testes and determine if sperm are present.
EVALUATION OF WOMEN — Although a variety of tests are available for evaluating female infertility, it may not be necessary to have all of these tests. Healthcare providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — A woman's past health and medical history may provide some clues about the cause of infertility. The healthcare provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications used; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility evaluations.
Physical examination — A physical examination usually includes a general examination, with special attention to any signs of hormone deficiency or signs of other conditions that might impair fertility. The provider will also perform a pelvic examination, which can identify abnormalities of the reproductive tract and signs of low hormone levels (show figure 2).
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; in women, key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
Tests to evaluate ovulation — Ovulation (the release of an egg from an ovary) is essential for fertility. Abnormalities of ovulation can often be determined from a woman's menstrual history or hormone levels such as the pre-ovulatory LH surge or luteal phase progesterone (show figure 3).
Menstrual history — Amenorrhea (absent menstrual periods) usually signals an absence of ovulation, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular ovulation; although oligomenorrhea does not make pregnancy impossible, it can interfere with the ability to become pregnant.
Basal body temperature — Monitoring of basal body temperature (measured before getting out of bed in the morning) was previously recommended to determine if ovulation occurred. A woman's temperature usually rises by 0.5ºF to 1.0ºF after ovulation. However, basal body temperature patterns can be difficult to interpret and are not generally recommended in the evaluation of infertility.
Hormone levels — Levels of luteinizing hormone (LH) rise abruptly approximately 38 hours before ovulation. This hormone surge can be detected using an over-the-counter urinary test kit. However, this kit fails to detect the hormone surge about 15 percent of the time. Therefore, a clinician may recommend a blood test to confirm ovulation.
Blood levels of the hormone progesterone are a more accurate indicator of ovulation. Normally, levels of progesterone rise after ovulation. Progesterone tests are usually performed 18 to 24 days after the first day of a menstrual period.
Tests to evaluate the uterus and fallopian tubes — Uterine abnormalities that can contribute to infertility include congenital structural abnormalities, such as a uterine septum (a band of tissue that makes the uterine cavity small) (show figure 4); abnormalities linked to exposure to diethylstilbestrol (DES) (a hormone used in the past to prevent miscarriage), which can cause a T-shaped uterus (show figure 5); fibroids; polyps; and structural abnormalities that can result from gynecologic procedures.
Scarring and obstruction of the fallopian tubes can occur as a result of pelvic inflammatory disease, endometriosis or pelvic adhesions (scar tissue) from abdominal infection or surgery.
Hysterosalpingography — Hysterosalpingogram (HSG) is used to help identify structural abnormalities of the uterus and fallopian tubes. It involves inserting a small catheter through the cervix and into the uterus. A liquid dye is injected through the catheter, which fills the uterus and fallopian tubes. An x-ray is taken after the dye is injected, which shows the outline of the uterus and tubes (show radiograph 1). An abnormally shaped uterus or blocked fallopian tube would be visible on the x-ray (show radiograph 2).
The test is done while the woman is awake and lying on an x-ray table. Most women experience moderate to severe pelvic cramps when the dye is injected, but this usually improves after five to 10 minutes. The test is usually performed five to seven days after the menstrual period (before ovulation has occurred).
Hysteroscopy — In a hysteroscopy, a small tube with a camera is inserted through the cervix and into the uterus. Air or fluid is injected to expand the uterus and to allow the physician to see inside the uterus.
A hysteroscopy is usually performed in women who are thought to have an abnormal uterus, based upon hysterosalpingogram or ultrasound; several structural abnormalities can be surgically treated during hysteroscopy. Hysteroscopy is performed as a day (outpatient) surgery. Sedation with regional anesthesia (local, epidural, or spinal anesthesia) or general anesthesia is used during the procedure.
Pelvic ultrasound — In a transvaginal ultrasound, a small ultrasound probe is inserted into the vagina; this provides a clearer image of the uterus and ovaries than ultrasound that is performed through the abdomen. It does not require that the patient is sedated or anesthetized, and has few to no risks. It is used to measure the size and shape of the uterus and ovaries, and to determine if there are structural abnormalities (such as fibroids or ovarian cysts). If abnormalities are seen, further testing may be needed.
Laparoscopy — During laparoscopy, a thin, lighted tube is inserted through a small incision in the abdomen, allowing the physician to view the uterus, ovaries, and fallopian tubes. Laparoscopy is performed as a day surgery procedure, and requires that the patient receive general anesthesia.
Laparoscopy can detect damage and obstruction of the fallopian tubes, endometriosis, and other abnormalities of the pelvic structures. It is the best test for diagnosis of endometriosis or pelvic adhesions (scarring). Furthermore, endometriosis can be treated during laparoscopy, which can help to improve pregnancy rates in women with infertility who have endometriosis. However, laparoscopy is not routinely done during an evaluation of infertility.
Genetic tests — Genetic testing may be recommended if there is a suspicion that genetic or chromosomal abnormalities are contributing to infertility. These tests usually require a small blood sample, which is sent to a laboratory for evaluation.
Although assisted reproductive techniques may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to educate a couple about the possibility of parent to child transmission, possible impact of the abnormality, and treatments available to prevent parent-to-child transmission.
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — The process of trying to become pregnant and the inability to do so can lead to a variety of emotions, including anxiety, depression, anger, shame, and guilt. In one study, 40 percent of infertility patients suffered with some type of psychiatric disorder; the most common diagnosis was an anxiety disorder (23 percent), followed by major depressive disorder (17 percent) [1].
Both men and women can suffer from these problems, which can further hinder a couple's ability to become pregnant. Psychological distress is associated with infertility treatment failure and interventions to relieve stress are associated with increased pregnancy rates.
The best approach for treatment of psychological distress related to infertility treatment has not been determined. However, some experts suggest relaxation techniques, stress-management, coping skills training, and group support. Evaluation by a psychiatrist may be needed for some persons with significant symptoms of anxiety or depression.
TREATMENT — There are a number of options for treatment of both male and female infertility. Separate topic reviews are available. (See "Patient information: Treatment of infertility in men" and see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
RESOLVE: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.org)
The Hormone Foundation
(www.hormone.org/public/other.cfm, available in English and Spanish)
[2-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chen, TH, Chang, SP, Tsai, CF, Juang, KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod 2004; 19:2313.
2. De Kretser, DM. Male infertility. Lancet 1997; 349:787.
3. De Kretser, DM, Baker, HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
4. Gray, RH. Epidemiology of infertility. Curr Opin Obstet Gynecol 1990; 2:154.
5. Guzick, DS, Grefenstette, I, Baffone, K, et al. Infertility evaluation in fertile women: A model for assessing the efficacy of infertility testing. Hum Reprod 1994; 9:2306.
6. Templeton, A, Fraser, C, Thompson, B. Infertility--epidemiology and referral practice. Hum Reprod 1991; 6:1391.
Vaginal hysterectomy
DEFINITION — Vaginal hysterectomy is a surgical procedure in which the uterus is removed through the vagina. One or both ovaries and fallopian tubes may be removed during the procedure, as well (show figure 1). A vaginal approach may be chosen if the uterus is not greatly enlarged, and if the condition prompting the surgery is benign and limited to the uterus. Studies have shown that vaginal hysterectomy has fewer complications, a shorter length of hospitalization, and faster recovery as compared to removal of the uterus through an abdominal incision (abdominal hysterectomy). (See "Patient information: Abdominal hysterectomy").
FEMALE ANATOMY — A brief review of female reproductive anatomy may be of help in understanding hysterectomy (show figure 2).
The uterus is a hollow, pear-shaped muscular organ located in the lower abdomen or pelvis. One end of each fallopian tube opens into the side of the uterus, at the upper end, and the other end lies next to an ovary. At its lower end, the uterus narrows and opens into the vagina. The lower end of the uterus is called the cervix. The ovaries lie next to and slightly behind the uterus.
REASONS FOR HYSTERECTOMY — A hysterectomy may be advised for a number of conditions. For some of these conditions, there may be alternatives to hysterectomy, which are described below. (See "Alternatives to hysterectomy" below).
Abnormal uterine bleeding — Excessive uterine bleeding, called menorrhagia, can lead to anemia (low blood iron count), fatigue, and contribute to missed days at work or school. Menorrhagia is generally defined as bleeding that lasts longer than seven days or saturates more than one pad per hour for several hours.
Irregular uterine bleeding, called metrorrhagia, can also occur in women with menorrhagia. Metrorrhagia is defined as bleeding or spotting that occurs at times other than during the expected menstrual period.
Menorrhagia and metrorrhagia are generally treated first with medication or other surgical alternatives to hysterectomy. (See "Patient information: Menorrhagia (Excessive menstrual bleeding)"). However, abnormal uterine bleeding that does not improve with conservative treatments may require hysterectomy.
Fibroids — Fibroids (also known as leiomyoma) are noncancerous growths of uterine muscle that occur in up to one-third of all women. Fibroids may become larger during pregnancy, and typically shrink after menopause. They may cause excessive and irregular vaginal bleeding. (See "Patient information: Fibroids").
Pelvic organ prolapse — Pelvic organ prolapse occurs due to stretching and weakening of the pelvic muscles and ligaments. This allows the uterus to fall (or prolapse) into the vagina. It is usually associated with pregnancy, vaginal childbirth, genetic factors, chronic constipation, or lifestyle factors (repeated heavy lifting over the lifetime).
Cervical abnormalities — Precancer or carcinoma in situ (CIN 3) of the cervix that does not resolve after other procedures (such as cone biopsy, laser or cryosurgery) may require hysterectomy. (See "Patient information: Screening for cervical cancer").
Endometrial hyperplasia — Endometrial hyperplasia is the term used to describe excessive growth of the endometrium (the tissue that lines the uterus). It can sometimes lead to endometrial cancer. Although endometrial hyperplasia can often be treated with medication, a hysterectomy is sometimes needed or preferred to medical therapy.
Chronic pelvic pain — Chronic pelvic pain can be due to the effects of endometriosis or scarring (adhesions) in the pelvis and between pelvic organs. However, pelvic pain can also be caused by other sources, including the gastrointestinal and urinary systems. (See "Patient information: Chronic pelvic pain in women"). It is important for a woman with pelvic pain to ask about the probability that her pain will improve after hysterectomy.
PRE-OPERATIVE PLANNING AND EVALUATION — Before surgery, there are two main decisions that need to be made: whether the ovaries should be removed, and whether estrogen replacement therapy is needed.
Removal of ovaries — A hysterectomy does not involve removing the ovaries, but they may be removed at the same time as hysterectomy; this procedure is known as oophorectomy. The decision to remove the ovaries depends upon several considerations. A list of questions to help make this decision may be found on the following table (show table 1). Occasionally, it may not be possible to remove the ovaries due to scar tissue or other factors that increase the risk of removal.
Premenopausal women may decide to keep the ovaries to provide a continued, natural source of hormones, including estrogen, progesterone, and testosterone. These hormones are important in maintaining sexual interest and preventing hot flashes and loss of bone density loss. On the other hand, women who have menstrual cycle-related migraines, epilepsy, or severe premenstrual syndrome may have an improvement in symptoms when hormone levels are reduced by removal of the ovaries. Individuals should discuss the risks and preferences with a doctor before surgery.
Postmenopausal women are usually advised to have their ovaries removed because of a small risk of developing ovarian cancer at some point during their lifetime. This benefit of removing the ovaries appears to outweigh the benefit of continued hormone production, as described above.
Estrogen replacement therapy — Estrogen replacement therapy (ERT) may be recommended after surgery for women who had their ovaries removed. Women who have not reached menopause may use ERT to avoid hot flashes, night sweats, and loss of bone density, which may occur when the ovaries are surgically removed. Women who plan to use ERT should talk with their clinician about the risks and benefits, and about how long to use this treatment.
In younger women who retain their ovaries, ERT may be needed at a later date if the ovaries stop functioning earlier than expected.
Women who have completed menopause generally do not require ERT after hysterectomy. (See "Patient information: Postmenopausal hormone therapy").
Pre-operative testing — Standard pre-operative testing may include a physical examination, EKG, chest x-ray, and blood testing, depending upon age and other medical conditions.
PROCEDURE — Vaginal hysterectomy is performed in a hospital setting, and generally requires one to two hours in the operating room. Patients are given general or spinal anesthesia plus sedation so that they feel no pain. Heart rate, blood pressure, blood loss, and respiration are closely observed throughout the procedure. After surgery, patients are transferred to the recovery room (also known as the post-anesthesia care unit) so that they can be monitored while waking up. Most patients will then be transferred to a hospital room and will stay one to two days.
LAPAROSCOPICALLY ASSISTED VAGINAL HYSTERECTOMY (LAVH) — Laparoscopically assisted vaginal hysterectomy (LAVH) is done by some surgeons to assist with the vaginal hysterectomy procedure. A laparoscope is a surgical instrument inserted through a small incision in the abdomen and pelvis. Using the scope, the surgeon can more easily see the uterus, ovaries, and the tissues that surround these organs within the pelvis (show figure 3).
In addition, instruments may be used, along with the laparoscope, to facilitate the removal of the uterus through the vagina. LAVH might be recommended for a woman with an enlarged uterus, history of prior pelvic surgery, endometriosis, or other factors that could complicate a traditional vaginal hysterectomy. Women generally recover faster after a vaginal hysterectomy or LAVH, as compared to women who have abdominal hysterectomy.
However, not all surgeons use laparoscopy since additional training, experience, and equipment is necessary. Patients should talk to their surgeon regarding the best procedure for their individual situation.
NEED FOR ABDOMINAL HYSTERECTOMY — After surgery has begun, the surgeon may find conditions, such as extensive scar tissue, that require him or her to make an abdominal incision to remove the uterus. Sometimes these conditions are not apparent before surgery.
COMPLICATIONS — A number of complications can occur as a result of hysterectomy. Fortunately, most can be easily managed and do not cause long-term problems.
Hemorrhage — Excessive bleeding (hemorrhage) occurs in a small number of cases. Excessive bleeding may require a blood transfusion and/or a return to the operating room to find and stop it.
Infection — Low-grade fever is common after hysterectomy, is not always caused by infection, and usually resolves without treatment. However, a high or persistent fever may signal an infection. Serious infection occurs in less than five percent of women, and can usually be treated with intravenous antibiotics. Much less commonly, patients require another surgical procedure.
Constipation — Constipation occurs in most women following hysterectomy, and can usually be controlled with a regimen of stool softeners, dietary fiber, and laxatives.
Urinary retention — Urinary retention, or the inability to pass urine, can occur after vaginal hysterectomy. Urine can be drained using a catheter until retention resolves, usually within 24 to 48 hours.
Blood clots — Pelvic surgery increases the risk of developing blood clots in the large veins of the leg or lung. The risk is increased for approximately six weeks after surgery. Medications may be given to some women to prevent blood clots. In addition, women taking oral contraceptives or hormone replacement should ideally discontinue them one month prior to surgery since they can further increase the risk of blood clots. Women who are sexually active and premenopausal should use alternative methods of birth control (e.g. condoms) to prevent pregnancy before surgery. (See "Patient information: Venous thrombosis").
Damage to adjacent organs — The urinary bladder, ureters (small tubes leading from the kidneys to the bladder), and large and small intestines are located in the lower abdomen and pelvis and can be injured during hysterectomy. Bladder injury occurs one to two percent of women who have vaginal hysterectomy, while bowel injury occurs in less than one percent of women. Injury can usually be detected and corrected at the time of surgery. If detected after surgery, another operation may be needed.
Early menopause — Women who have undergone hysterectomy may experience menopause earlier than the average age of menopause (age 51). This may be due to an interruption in blood flow to the ovaries as a result of removing the uterus.
RECOVERY AFTER SURGERY — Fluids and food are generally offered soon after surgery. Intravenous (IV) fluids may be administered during the first day, particularly if there is nausea or vomiting. Pain medicine is given as needed, either intravenously, or by intramuscular (IM) injection or pill. Patients are encouraged to resume their normal daily activities as soon as possible. Regaining mobility is particularly important since it helps to prevent complications, such as blood clots, pneumonia, and gas pains.
Walking and stair climbing are encouraged; tub baths and showers are permitted. Driving should be avoided until full mobility returns and narcotic pain relievers are no longer required.
To minimize stress on the healing tissues, patients will be asked to avoid lifting greater than 20 pounds (9 kg) for four to six weeks after surgery. Vaginal intercourse, tampons, and douching are not recommended for the same time period to allow complete healing.
A patient should call her surgeon if she experiences pain that is not relieved with medication, persistent nausea or vomiting, bleeding heavier than a menstrual period, fever greater than 101º F or 38º C, foul-smelling vaginal discharge, or inability to empty the bladder or bowels.
Constipation is common after surgery and while using narcotic pain medications, and can often be controlled with stool-softening medications such as Colace® (docusate sodium) and stool bulking agents such as psyllium (Metamucil®), methylcellulose (Citrucel®), or calcium polycarbophil (FiberCon®). (See "Patient information: Constipation in adults"). A woman who does not have a bowel movement within 3 days should contact her surgeon for further advice.
Normal activities can be resumed gradually over a six-week period. Patients may return to work as soon as they have sufficient stamina and mobility.
LIFE AFTER HYSTERECTOMY — Studies of women's response to hysterectomy show that most women are very satisfied with their results (show table 2). Most reported improvement in symptoms directly related to the uterus, including pain and vaginal bleeding.
Sexual function and enjoyment, interest in sex, and pain with sex were improved for most women. However, this improvement may be dependent upon several factors, including the age of a woman at the time of surgery, the reason for surgery, and history of any prior difficulties with mood. Younger women may grieve after hysterectomy due to their loss of fertility. A woman who has new feelings of sadness, anxiety, or depression after surgery should speak with her healthcare provider. These feelings may be treated by talking with a therapist, with antidepressant medication, or may resolve with time.
ALTERNATIVES TO HYSTERECTOMY — Some women who wish to avoid or postpone hysterectomy may use medications or less invasive surgical procedures. Medical and surgical alternatives to hysterectomy depend upon the underlying disorder. The decision as to which treatment is "best" should be based upon a woman's particular medical problem, all available treatment options, and the risks and benefits of each type of treatment.
Some alternatives to vaginal hysterectomy include the following: Uterine artery embolization and myomectomy may be used to treat symptomatic leiomyoma (fibroids). (See "Patient information: Fibroids"). Pain clinics may be able to treat patients with severe and chronic pelvic pain without surgery. (See "Patient information: Chronic pelvic pain in women"). Endometrial ablation, in which a physician destroys or removes most of the endometrium using an instrument inserted through the vagina and cervix and into the uterus. (See "Patient information: Menorrhagia (Excessive menstrual bleeding)"). Medical therapy using hormonal medications, such GnRH analogs (for example, leuprolide) or progestins can help reduce the pain associated with endometriosis. (See "Patient information: Endometriosis"). Cone biopsy (eg, cold knife cone), cryosurgery, laser surgery, or loop electrocautery (eg, LEEP or LLETZ) are usually used to treat women with high-grade cervical intraepithelial neoplasia or carcinoma in situ of the cervix. These procedures remove the abnormal part of the cervix rather than the entire cervix and uterus (See "Patient information: Screening for cervical cancer").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The American College of Obstetricians and Gynecologists
(www.acog.org)
U.S. Department of Health & Human Services, Federal Government Source for Women's Health Information
(www.4woman.gov)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Meeks, GR, Harris, RL. Surgical approach to hysterectomy: Abdominal, Laparoscopy-assisted, or vaginal. Clin Obstet Gynecol 1997; 40:886.
2. Harris, WJ. Complications of hysterectomy. Clin Obstet Gynecol 1997; 40:928.
3. Carlson, KJ, Miller, BA, Fowler, FJ, Jr. the Maine Women's Health Study I: Outcomes of hysterectomy. Obstet Gynecol 1994; 83:556.
4. Rhodes, JC, Kjerulff, KH, Langenberg, PW, Guzinski, GM. Hysterectomy and sexual functioning. JAMA 1999; 282:1934.
FEMALE ANATOMY — A brief review of female reproductive anatomy may be of help in understanding hysterectomy (show figure 2).
The uterus is a hollow, pear-shaped muscular organ located in the lower abdomen or pelvis. One end of each fallopian tube opens into the side of the uterus, at the upper end, and the other end lies next to an ovary. At its lower end, the uterus narrows and opens into the vagina. The lower end of the uterus is called the cervix. The ovaries lie next to and slightly behind the uterus.
REASONS FOR HYSTERECTOMY — A hysterectomy may be advised for a number of conditions. For some of these conditions, there may be alternatives to hysterectomy, which are described below. (See "Alternatives to hysterectomy" below).
Abnormal uterine bleeding — Excessive uterine bleeding, called menorrhagia, can lead to anemia (low blood iron count), fatigue, and contribute to missed days at work or school. Menorrhagia is generally defined as bleeding that lasts longer than seven days or saturates more than one pad per hour for several hours.
Irregular uterine bleeding, called metrorrhagia, can also occur in women with menorrhagia. Metrorrhagia is defined as bleeding or spotting that occurs at times other than during the expected menstrual period.
Menorrhagia and metrorrhagia are generally treated first with medication or other surgical alternatives to hysterectomy. (See "Patient information: Menorrhagia (Excessive menstrual bleeding)"). However, abnormal uterine bleeding that does not improve with conservative treatments may require hysterectomy.
Fibroids — Fibroids (also known as leiomyoma) are noncancerous growths of uterine muscle that occur in up to one-third of all women. Fibroids may become larger during pregnancy, and typically shrink after menopause. They may cause excessive and irregular vaginal bleeding. (See "Patient information: Fibroids").
Pelvic organ prolapse — Pelvic organ prolapse occurs due to stretching and weakening of the pelvic muscles and ligaments. This allows the uterus to fall (or prolapse) into the vagina. It is usually associated with pregnancy, vaginal childbirth, genetic factors, chronic constipation, or lifestyle factors (repeated heavy lifting over the lifetime).
Cervical abnormalities — Precancer or carcinoma in situ (CIN 3) of the cervix that does not resolve after other procedures (such as cone biopsy, laser or cryosurgery) may require hysterectomy. (See "Patient information: Screening for cervical cancer").
Endometrial hyperplasia — Endometrial hyperplasia is the term used to describe excessive growth of the endometrium (the tissue that lines the uterus). It can sometimes lead to endometrial cancer. Although endometrial hyperplasia can often be treated with medication, a hysterectomy is sometimes needed or preferred to medical therapy.
Chronic pelvic pain — Chronic pelvic pain can be due to the effects of endometriosis or scarring (adhesions) in the pelvis and between pelvic organs. However, pelvic pain can also be caused by other sources, including the gastrointestinal and urinary systems. (See "Patient information: Chronic pelvic pain in women"). It is important for a woman with pelvic pain to ask about the probability that her pain will improve after hysterectomy.
PRE-OPERATIVE PLANNING AND EVALUATION — Before surgery, there are two main decisions that need to be made: whether the ovaries should be removed, and whether estrogen replacement therapy is needed.
Removal of ovaries — A hysterectomy does not involve removing the ovaries, but they may be removed at the same time as hysterectomy; this procedure is known as oophorectomy. The decision to remove the ovaries depends upon several considerations. A list of questions to help make this decision may be found on the following table (show table 1). Occasionally, it may not be possible to remove the ovaries due to scar tissue or other factors that increase the risk of removal.
Premenopausal women may decide to keep the ovaries to provide a continued, natural source of hormones, including estrogen, progesterone, and testosterone. These hormones are important in maintaining sexual interest and preventing hot flashes and loss of bone density loss. On the other hand, women who have menstrual cycle-related migraines, epilepsy, or severe premenstrual syndrome may have an improvement in symptoms when hormone levels are reduced by removal of the ovaries. Individuals should discuss the risks and preferences with a doctor before surgery.
Postmenopausal women are usually advised to have their ovaries removed because of a small risk of developing ovarian cancer at some point during their lifetime. This benefit of removing the ovaries appears to outweigh the benefit of continued hormone production, as described above.
Estrogen replacement therapy — Estrogen replacement therapy (ERT) may be recommended after surgery for women who had their ovaries removed. Women who have not reached menopause may use ERT to avoid hot flashes, night sweats, and loss of bone density, which may occur when the ovaries are surgically removed. Women who plan to use ERT should talk with their clinician about the risks and benefits, and about how long to use this treatment.
In younger women who retain their ovaries, ERT may be needed at a later date if the ovaries stop functioning earlier than expected.
Women who have completed menopause generally do not require ERT after hysterectomy. (See "Patient information: Postmenopausal hormone therapy").
Pre-operative testing — Standard pre-operative testing may include a physical examination, EKG, chest x-ray, and blood testing, depending upon age and other medical conditions.
PROCEDURE — Vaginal hysterectomy is performed in a hospital setting, and generally requires one to two hours in the operating room. Patients are given general or spinal anesthesia plus sedation so that they feel no pain. Heart rate, blood pressure, blood loss, and respiration are closely observed throughout the procedure. After surgery, patients are transferred to the recovery room (also known as the post-anesthesia care unit) so that they can be monitored while waking up. Most patients will then be transferred to a hospital room and will stay one to two days.
LAPAROSCOPICALLY ASSISTED VAGINAL HYSTERECTOMY (LAVH) — Laparoscopically assisted vaginal hysterectomy (LAVH) is done by some surgeons to assist with the vaginal hysterectomy procedure. A laparoscope is a surgical instrument inserted through a small incision in the abdomen and pelvis. Using the scope, the surgeon can more easily see the uterus, ovaries, and the tissues that surround these organs within the pelvis (show figure 3).
In addition, instruments may be used, along with the laparoscope, to facilitate the removal of the uterus through the vagina. LAVH might be recommended for a woman with an enlarged uterus, history of prior pelvic surgery, endometriosis, or other factors that could complicate a traditional vaginal hysterectomy. Women generally recover faster after a vaginal hysterectomy or LAVH, as compared to women who have abdominal hysterectomy.
However, not all surgeons use laparoscopy since additional training, experience, and equipment is necessary. Patients should talk to their surgeon regarding the best procedure for their individual situation.
NEED FOR ABDOMINAL HYSTERECTOMY — After surgery has begun, the surgeon may find conditions, such as extensive scar tissue, that require him or her to make an abdominal incision to remove the uterus. Sometimes these conditions are not apparent before surgery.
COMPLICATIONS — A number of complications can occur as a result of hysterectomy. Fortunately, most can be easily managed and do not cause long-term problems.
Hemorrhage — Excessive bleeding (hemorrhage) occurs in a small number of cases. Excessive bleeding may require a blood transfusion and/or a return to the operating room to find and stop it.
Infection — Low-grade fever is common after hysterectomy, is not always caused by infection, and usually resolves without treatment. However, a high or persistent fever may signal an infection. Serious infection occurs in less than five percent of women, and can usually be treated with intravenous antibiotics. Much less commonly, patients require another surgical procedure.
Constipation — Constipation occurs in most women following hysterectomy, and can usually be controlled with a regimen of stool softeners, dietary fiber, and laxatives.
Urinary retention — Urinary retention, or the inability to pass urine, can occur after vaginal hysterectomy. Urine can be drained using a catheter until retention resolves, usually within 24 to 48 hours.
Blood clots — Pelvic surgery increases the risk of developing blood clots in the large veins of the leg or lung. The risk is increased for approximately six weeks after surgery. Medications may be given to some women to prevent blood clots. In addition, women taking oral contraceptives or hormone replacement should ideally discontinue them one month prior to surgery since they can further increase the risk of blood clots. Women who are sexually active and premenopausal should use alternative methods of birth control (e.g. condoms) to prevent pregnancy before surgery. (See "Patient information: Venous thrombosis").
Damage to adjacent organs — The urinary bladder, ureters (small tubes leading from the kidneys to the bladder), and large and small intestines are located in the lower abdomen and pelvis and can be injured during hysterectomy. Bladder injury occurs one to two percent of women who have vaginal hysterectomy, while bowel injury occurs in less than one percent of women. Injury can usually be detected and corrected at the time of surgery. If detected after surgery, another operation may be needed.
Early menopause — Women who have undergone hysterectomy may experience menopause earlier than the average age of menopause (age 51). This may be due to an interruption in blood flow to the ovaries as a result of removing the uterus.
RECOVERY AFTER SURGERY — Fluids and food are generally offered soon after surgery. Intravenous (IV) fluids may be administered during the first day, particularly if there is nausea or vomiting. Pain medicine is given as needed, either intravenously, or by intramuscular (IM) injection or pill. Patients are encouraged to resume their normal daily activities as soon as possible. Regaining mobility is particularly important since it helps to prevent complications, such as blood clots, pneumonia, and gas pains.
Walking and stair climbing are encouraged; tub baths and showers are permitted. Driving should be avoided until full mobility returns and narcotic pain relievers are no longer required.
To minimize stress on the healing tissues, patients will be asked to avoid lifting greater than 20 pounds (9 kg) for four to six weeks after surgery. Vaginal intercourse, tampons, and douching are not recommended for the same time period to allow complete healing.
A patient should call her surgeon if she experiences pain that is not relieved with medication, persistent nausea or vomiting, bleeding heavier than a menstrual period, fever greater than 101º F or 38º C, foul-smelling vaginal discharge, or inability to empty the bladder or bowels.
Constipation is common after surgery and while using narcotic pain medications, and can often be controlled with stool-softening medications such as Colace® (docusate sodium) and stool bulking agents such as psyllium (Metamucil®), methylcellulose (Citrucel®), or calcium polycarbophil (FiberCon®). (See "Patient information: Constipation in adults"). A woman who does not have a bowel movement within 3 days should contact her surgeon for further advice.
Normal activities can be resumed gradually over a six-week period. Patients may return to work as soon as they have sufficient stamina and mobility.
LIFE AFTER HYSTERECTOMY — Studies of women's response to hysterectomy show that most women are very satisfied with their results (show table 2). Most reported improvement in symptoms directly related to the uterus, including pain and vaginal bleeding.
Sexual function and enjoyment, interest in sex, and pain with sex were improved for most women. However, this improvement may be dependent upon several factors, including the age of a woman at the time of surgery, the reason for surgery, and history of any prior difficulties with mood. Younger women may grieve after hysterectomy due to their loss of fertility. A woman who has new feelings of sadness, anxiety, or depression after surgery should speak with her healthcare provider. These feelings may be treated by talking with a therapist, with antidepressant medication, or may resolve with time.
ALTERNATIVES TO HYSTERECTOMY — Some women who wish to avoid or postpone hysterectomy may use medications or less invasive surgical procedures. Medical and surgical alternatives to hysterectomy depend upon the underlying disorder. The decision as to which treatment is "best" should be based upon a woman's particular medical problem, all available treatment options, and the risks and benefits of each type of treatment.
Some alternatives to vaginal hysterectomy include the following: Uterine artery embolization and myomectomy may be used to treat symptomatic leiomyoma (fibroids). (See "Patient information: Fibroids"). Pain clinics may be able to treat patients with severe and chronic pelvic pain without surgery. (See "Patient information: Chronic pelvic pain in women"). Endometrial ablation, in which a physician destroys or removes most of the endometrium using an instrument inserted through the vagina and cervix and into the uterus. (See "Patient information: Menorrhagia (Excessive menstrual bleeding)"). Medical therapy using hormonal medications, such GnRH analogs (for example, leuprolide) or progestins can help reduce the pain associated with endometriosis. (See "Patient information: Endometriosis"). Cone biopsy (eg, cold knife cone), cryosurgery, laser surgery, or loop electrocautery (eg, LEEP or LLETZ) are usually used to treat women with high-grade cervical intraepithelial neoplasia or carcinoma in situ of the cervix. These procedures remove the abnormal part of the cervix rather than the entire cervix and uterus (See "Patient information: Screening for cervical cancer").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The American College of Obstetricians and Gynecologists
(www.acog.org)
U.S. Department of Health & Human Services, Federal Government Source for Women's Health Information
(www.4woman.gov)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Meeks, GR, Harris, RL. Surgical approach to hysterectomy: Abdominal, Laparoscopy-assisted, or vaginal. Clin Obstet Gynecol 1997; 40:886.
2. Harris, WJ. Complications of hysterectomy. Clin Obstet Gynecol 1997; 40:928.
3. Carlson, KJ, Miller, BA, Fowler, FJ, Jr. the Maine Women's Health Study I: Outcomes of hysterectomy. Obstet Gynecol 1994; 83:556.
4. Rhodes, JC, Kjerulff, KH, Langenberg, PW, Guzinski, GM. Hysterectomy and sexual functioning. JAMA 1999; 282:1934.
Subscribe to:
Posts (Atom)