September 14, 2011

Infertility is defined as the inability of a sexually active, noncontracepting couple to achieve pregnancy in one year, the time to which about 90% of couples succeed. Among couples of reproductive age, about 10% are infertile. Delayed marriage and childbirth is one of the main social factors that has resulted in increased infertility in society. Furthermore, sexually transmitted diseases still are the major cause of infertility in Western countries.


The most common causes of infertility are: tubal disease, male disorders, lack of ovulation (anovulation), and abnormality of uterine tissue (endometriosis). The initial evaluation of infertility requires complete history of medical and surgical problems, a genetic history, a history of any sexually transmitted diseases, family history of early menopause, medication used, and allergies. Specific attention should be placed on details of potential occupational exposure to toxins as well as recreational drugs, smoking, and alcohol. All these questions apply to the male as well. Specific gender-oriented questions include menstrual abnormalities, history of milky discharge from the breasts (galactorrhea), abnormal, excessive body/ facial hair (hirsutism), acne in women, and erection abnormalities and genital trauma in men.

Tubal Disease

Tubal disease that is a cause of infertility is the result of a sexual transmitted disease. It is generally accepted that tubal infertility developed in 12% of women after one episode of pelvic inflammatory disease (PID), 24% after two episodes of PID, and 48% after three episodes of PID. The most common organism involved is the bacterium Chlamydia trachomatis. In dealing with the reproductive health of a young woman, it is essential that the patient is informed of these risks and appropriately screened.

A specialized procedure to evaluate the health of the tubes leading to the uterus, the hysterosalpingogram (HSG), is used to assess the presence of tubal disease. It is performed in the follicular phase of the menstrual cycle. If the history suggests PID, a specialized blood test (sedimentation rate) should be performed. If elevated, the test should be postponed. If normal, then the patient should be given prophylactic antibiotic, doxycycline 100 mg twice a day, starting 2 days before the procedure.

The treatment of tubal disease depends on the severity. Mild disease can be treated surgically, More advanced disease is treated with in vitro fertilization (IVF). Treatment of tubal disease is associated with an increased risk of pregnancy outside of the uterus (ectopic pregnancy).

Anovulation and Ovulatory Dysfunction

Anovulation and other disturbances of ovulation are another important cause of infertility. There are several methods to evaluate ovulation. Basal body temperature charts are inexpensive and sometimes useful. Many patients find them cumbersome. There is a tendency to overinterpret data from these charts. A reasonable screening test would be a single blood progesterone (a type of hormone) level timed on the basis of a home urinary test. A serum level above 10 ng/ml is usually associated with normal ovulatory cycle. If anovulation is detected, then blood testing should be ordered to rule out thyroid disease, pituitary abnormality, and premature ovarian failure.

The most common cause of anovulation is polycystic ovarian syndrome (PCOS). This syndrome is defined as irregular menstrual periods associated with clinical or biochemical evidence of an abnormal endocrine state (hyperandrogenism). The onset is usually at the time of puberty. Many women with PCOS have insulin resistance that is independent of weight. These patients often have a family history of diabetes and are at greater risk to develop non-insulindependent diabetes at a younger age than the general population. Obesity is a comorbid condition that accentuates the syndrome. Evaluation of these patients includes measurement of serum hormones (androgens and gonadotropins), exclusion of thyroid disease, and elevation in the hormone prolactin (hyperprolactinemia). These patients should have a simple measure of insulin resistance, such as fasting glucose and insulin.

The first treatment approach with PCOS patients is diet and exercise to modify insulin resistance. Many patients will achieve pregnancy spontaneously. If this is insufficient, oral glucose-lowering drugs such as metformin may be used. If this is unsuccessful, clomiphene citrate, a medication that is commonly used for ovulation induction, can be used.


Endometriosis is the presence of abnormal uterine tissue (endometrial glands and stroma) at sites outside the uterus. This disease affects many women in the reproductive age group and is a common cause of infertility. Although its etiology has not been conclusively identified, it is generally believed to involve abnormalities in the immune system. It is unclear whether this is causal or simply a response to abnormal implants.

Endometriosis is associated with painful periods (dysmenorrhea), painful intercourse (dyspareunia), noncyclical pelvic pain, and infertility. Many patients with endometriosis-associated infertility do not have significant pain symptoms. The extent of disease is evaluated by a numerical system that involves the presence of endometriosis in the pelvis, or ovaries, and the presence of fibrous growths (adhesions). It is unclear how early stage disease can cause infertility. Advanced disease causes a significant distortion of the pelvic cavity that clearly results in infertility.

Medical suppressive therapy, such as with luteinizing hormone-releasing hormone agonist (LHRHa), does not improve fertility. However, surgical therapy for early stage disease has been shown in a randomized clinical trial to improve fertility. Advanced disease can be initially treated with surgery to restore normal anatomy. However, recurrent advanced endometriosis is best treated with IVF.


Leiomyomas are a type of benign tumor. They have a high prevalence in some ethnic groups, such as African Americans. Leiomyomas are not common causes of infertility. Investigation for infertility in patients with leiomyomas should proceed as in other patients with infertility. If there is distortion of the uterine cavity, then myomectomy (removal of abnormal tissue) may improve fertility. A woman should be counseled that adhesions may form and there may be an increased incidence of rupture of the uterus during pregnancy.

Male Infertility

Male factor infertility remains a significant problem contributing to approximately 50% of the cases attending infertility clinics. Male infertility involves a complex series of events, wherein abnormalities in one or more steps block the ability to initiate a viable pregnancy.

Male infertility is a multifactorial syndrome encompassing a variety of disorders. In more than half of infertile men, the cause of their infertility is unknown and could be congenital or acquired. The known causes of male infertility are quite numerous, including factors that prevent normal function of sex organs (pretesticular causes such as excess estrogen), disorders of the testicles such as abnormal maturation of the testes, and posttesticular causes such as abnormal sperm motility (movement).


Laboratory testing provides additional insight into both the extent and mechanism of testicular dysfunction. The hormonal profile is essential in differentiating causes of infertility. Very low sperm counts can be associated with chromosomal abnormalities. These have been detected in about 10-15% of males with some types of sperm abnormalities.

In the majority of infertile men, detailed semen analyses are required to fully characterize their reproductive dysfunction. Conventionally, semen analysis includes measurement of sperm concentration, semen volume, percentage of motile sperm, and quality of forward progression of these motile sperm, viability, and morphology. Computer-assisted semen analysis (CASA) provides more sophisticated measures of sperm motion, such as velocity, linearity, and lateral head displacement.


The therapy for infertility has evolved immensely in the last 10 years. Ovulation induction drugs have not changed dramatically in the last 20 years. There are antiestrogens such as clomiphene citrate and gonadotropins. The most recent change in gonadotropin therapy is that most of these drugs are now synthetic rather than derived from human products. Surgery does not have as dominant a role and has been supplanted by assisted reproductive technologies. The main indications for surgery are leiomyomas and endometriosis.

SEE ALSO: Endometriosis, Fecundity, Reproductive technologies

Suggested Reading

  • Clark, A. M., Thornley, B., Tomlinson, L., Galletley, C., & Norman, R. J. (1998). Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Human Reproduction, 13, 1502—1505.
  • Falcone, T., Goldberg, J. M., & Miller, K. F. (1996). Endometriosis: Medical and surgical intervention. Current Opinion in Obstetrics and Gynecology, 8, 178—183.
  • Hatch, E. E., & Bracken, M. B. (1993). Association of delayed conception with caffeine consumption. American Journal of Epidemiology, 138, 1082-1092.
  • Legro, R. S., Finegood, D., & Dunaif, A. (1998). A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism, 83, 2694-2698.
  • Pagidas, K., Falcone, T., Hemmings, R., & Miron, R. (1996). Comparison of surgical treatment of moderate (stage iii) and severe (stage iv) endometriosis-related infertility with IVF_ET. Fertility and Sterility, 65, 791-795.
  • Rowe, P., Comhaire, F., Hargreave, T. B., & Mahmoud, A. M. (Eds.). (2000). WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge, UK: Cambridge University Press.
  • Sharara, F. L., Scott, R. T., Jr., & Seifer, D. B. (1998). The detection of diminished ovarian reserve in infertile women. American Journal of Obstetrics and Gynecology, 179, 804-812.


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