The fallopian tubes. When menstruation is normal, evaluate the fallopian tubes and their patency; 30% to 40% of infertility cases can be related to peritoneal pathology.3,7 Inability to conceive in a previous relationship, history of PID, or prior tubal surgery all correlate to infertility. Ten percent of patients with a history of one PID episode and 54% to 75% of patients with 3 episodes will have patency issues.7
Consider arranging for a hysterosalpingogram (HSG) in all patients as part of an initial work-up for infertility.8 HSG is useful in evaluating tubal patency and the uterine cavity, and it can be therapeutic. HSG is not useful in detecting peritubal adhesions or endometriosis; patients in whom you suspect these conditions should undergo diagnostic laparoscopy. If abnormalities are found on HSG, refer patients to a reproductive endocrinologist to evaluate treatment options.
Chlamydia trachomatis IgG antibody testing can predict the presence of tubal disease. For women with low risk of tubal disease, it may be more cost effective to test for the Chlamydia antibody and proceed with HSG if the result is positive. Antibody testing is also useful for women with an allergy to contrast dye who cannot undergo an HSG. If the antibody test result is positive, consider arranging for a sonohysterogram to evaluate for the presence of fluid in the cul-de-sac, or an intrauterine infusion of saline to evaluate the patency of at least one tube.9
Ovulatory function. To assess ovulatory function, measure a midluteal-phase serum progesterone level, drawn 1 week before the expected day of menses (Day 21 of a 28-day cycle). A level >3 ng/mL is evidence of ovulation. Over-the-counter ovulation kits detect the luteinizing hormone (LH) surge but have false-positive and false-negative rates of 5% to 10%, respectively.10 Recording basal body temperature is a noninvasive and inexpensive means of evaluating ovulation. The patient must record temperatures at exactly the same time each day. Have her log the temperatures and watch for a spike that occurs 1 to 2 days after the LH surge. The average woman’s temperature rises above 98ºF in progressing from the follicular to the luteal phase. Since the spike occurs 1 to 2 days after ovulation, this method is best used for many months so the woman can predict her cycle.11
Once timing of ovulation has been established, you can check lab results at Day 3 of the woman’s cycle for follicle-stimulating hormone (FSH), LH, estradiol, thyroid-stimulating hormone (TSH), prolactin, and 2-hour fasting glucose tolerance. In addition to polycystic ovarian syndrome (PCOS), patients may have ovulatory dysfunction secondary to glucose intolerance.
A clomiphene (Clomid) challenge can help in assessing ovarian reserve. Administer 100 mg clomiphene on Days 5 through 9 of the patient’s cycle, and check FSH and estradiol levels on Day 10. With diminished ovarian reserve, FSH will increase to >12 mIU/mL and estradiol to >300 pg/mL.12 If this occurs, consider referring for an ultrasound measurement of antral follicle count. The presence of 4 to 10 follicles measuring 2 to 10 mm in diameter suggests adequate reserve.13
Although not widely available in the United States, the test for antimüllerian hormone (AMH) levels may be useful in reflecting the size of the primordial follicle pool. At menopause, the level is undetectable. A level above 0.5 ng/mL correlates with good ovarian reserve; levels <0.15 ng/mL suggest poor response to in vitro fertilization (IVF).14
Endocrine factors account for 45% to 55% of female infertility and include thyroid disease, PCOS, diabetes mellitus, prolactinemia, and luteal phase defects. Subclinical hypothyroidism, often evidenced only by high levels of TSH, decreases the chance of a successful pregnancy. This can occur even if the dysfunction is not severe enough to affect cycle regularity.15 Clinical hypo- or hyperthyroidism can affect ovulation by interfering with normal hormonal feedback loops, and correcting thyroid disease can improve fertility.
Galactorrhea discovered during the history and physical may be caused by elevated prolactin levels, which also inhibit normal ovulatory function. Chronically elevated prolactin levels in patients with PCOS can be attributed to elevated estrogen levels. Adiposity, acne, and hirsutism with menstrual irregularity can indicate PCOS as the primary cause, and your work-up should focus on a hyperandrogenic state.16 Low or normal FSH levels are common in patients with PCOS. Also test for 17a-hydroxyprogestrone and serum testosterone levels.17
Endometriosis. How endometriosis affects fertility is controversial. One hypothesis is that it is associated with overproduction of prostaglandins, metalloproteinases, cytokines, and chemokines. The inflammatory process impairs ovarian, peritoneal, tubal, and endometrial function.18