At a Glance

The definition of infertility is the inability to conceive after 1 year of unprotected intercourse. Infertility can be classified as primary, when no previous successful pregnancies have occurred, or secondary, when there have been previous conceptions. The most common causes for infertility are hormonal abnormalities of the hypothalamic-pituitary-gonadal axis. In addition, anatomic abnormalities, autoimmune disorders, or drugs/chemicals can also affect fertility.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Male Infertility

Male infertility can be caused by endocrine disorders, anatomic abnormalities, abnormal spermatogenesis, abnormal sperm motility, iatrogenic causes, or psychosocial disorders. Evaluation of male infertility should start with a complete history and physical examination, including history of drug/chemical exposure and sexual history. From the laboratory standpoint, semen analysis, endocrine testing, and immunological testing should be performed. If the semen analysis is abnormal, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T) should be measured. Measuring antisperm antibodies is not recommended, because the concentration at which these antibodies inhibit fertility is unknown.(Table 1)

Table 1.
Test/Analyte Pattern Possible Dx
¯LH, ¯FSH, ¯T Hypogonadotropic hypogonadism(Hypothalamic or pituitary failure)
LH, FSH, ¯T Hypergonadotropic hypogonadism(Gonadal failure)
LH, Normal FSH, Normal or T Androgen resistance
Female Infertility

Female infertility can be due to ovulatory disorders, pelvic abnormalities, and immunological factors. As with male infertility, a detailed history and physical exam should be the first step. Here, we discuss laboratory assessment of ovulatory disorders and immunological factors.

The primary laboratory test to assess ovulation is serum progesterone. Progesterone increases immediately following ovulation, at the beginning of the luteal phase, peaks at about 8 days after ovulation (days 21-23 of the menstrual cycle), and falls before the beginning of the next cycle. Testing should be performed during this peak period (days 21-23 of menstrual cycle). Mid-luteal peak progesterone concentrations greater than 10 ng/mL indicate normal ovulation. Peak progesterone concentrations less than 10 ng/mL are suggestive of either inadequate luteal phase progesterone production or inappropriate timing of collection.

Endocrine evaluation should include serum gonadotropins (LH, FSH), prolactin, TSH, testosterone and estradiol. Measurement of basal FSH can indicate relative ovarian age. Concentrations greater than 20 IU/L are associated with a sharp reduction in successful pregnancy. Increases in FSH and LH are an indication of hypergonadotropic hypogonadism, whereas decreases in these hormones could indicate hypogonadotropic hypogonadism.(Table 2)

Table 2.
Test/Analyte Pattern Possible Dx
FSH (>30 IU/mL) Hypergonadotropic hypogonadism(Advanced ovarian age, ovarian failure)
¯Estradiol (<40 pg/mL), ¯LH (<10 IU/L), ¯FSH (<10 IU/L) Hypogonadotropic hypogonadism(pituitary failure)
Prolactin, FSH (>30 IU/L), ¯Estradiol (<20 pg/mL) Hyperprolactinemia
LH, ¯ or Norm FSH, testosterone Polycystic Ovarian Syndrome (PCOS)

Testing for FSH, estradiol, and inhibin B concentrations can help determine ovarian reserve in women in their mid-30s to early 40s. These are measured on day 3 of the menstrual cycle. FSH concentrations greater than 20 IU/mL and estradiol greater than 75 pg/mL are associated with poor reproductive outcome. Inhibin B concentrations greater than 45 pg/mL have better pregnancy rates than inhibin B concentrations less than 45 pg/mL.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Timing of collection is important because of the cyclical patterns and diurnal variations of these hormones. Serum progesterone should be collected at its peak, on days 21-23 of the menstrual cycle. Inappropriate timing of collection can give a falsely low progesterone result. Testosterone should be measured at its peak, in the morning (between 4 AM and 8AM).(Table 3)

Table 3.
Hormone tested Drug Change
LH Anticonvulsants
Clomiphene Increase
Oral contraceptives
Digoxin Decrease
Hormone Treatments
FSH Cimetidine
Cloniphene Increase
Oral contraceptives
Hormone treatments Decrease
Estradiol Glucorticosteroids
Estrogen containing drugs Increase
Clomiphene Decrease
Oral contraceptives
Testosterone Anticonvulsants
Barbiturates Increase
Estrogen therapy
Marijuana Decrease
Prolactin Methyldopa
Dopamine antagonists Increase
Levodopa Decrease
Ergot alkaloid derivatives
TSH Iodine
Aluminum hydroxyde Increase
Ferrous sulfate
Iron sucralfate
Glucocorticoids Decrease

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

For male infertility, the most important test is semen analysis, as this will be the first step in the evaluation.

For female infertility, if there is primary amenorrhea, a rare form of congenital adrenal hyperplasia (CAH) involving 17α-hydroxylase deficiency should be considered. This can be tested by measuring concentrations of serum progesterone (>3 ng/ml), 17-hydroxyprogesterone (<0.2, aldosterone (low), 11-doxycorticosterone (high), testosterone (low), estradiol (low), and DHEA-S (low). In addition, an adrenocorticotropic hormone (ACTH) stimulation test can confirm the diagnosis. Low cortisol is suggestive of CAH.

For evaluation of secondary amenorrhea, cortisol measurement for suspected Cushing’s syndrome should be performed. For hirsutism and virilization, evaluation should start with testing free testosterone and DHEA-S concentrations. High DHEA-S will indicate adrenal origin of androgens, and high testosterone will suggest adrenal or ovarian origin of androgens. Polycystic ovary syndrome (PCOS) is suspected when elevated concentrations of androgens are present. Increase in free testosterone concentrations and decrease in sex hormone binding globulin (SHBG) are seen in PCOS patients.