An initial infertility evaluation is traditionally begun after one year of unprotected intercourse; however, an earlier evaluation may be indicated for increased maternal age, irregular menstrual cycles, previous pelvic inflammatory disease (pelvic inflammatory disease) or pelvic surgery.
One of the most important aspects of evaluating infertility is obtaining a thorough history from both partners. When evaluating the female partner, it is important to include the items listed in Table: Evaluation of female partner. When evaluating the male partner, it is important to include the items listed in Table: Evaluation of male partner.
Table: Evaluation of female partner
|General Category||Specific Points|
|Length of infertility||Coital frequency, previous treatment|
|Gravity and parity||History of spontaneous pregnancy, specific pregnancy outcomes, complications, history of recurrent pregnancy loss|
|Menstrual history||Length of cycles (normal 21-35 days), duration and type of flow (may indicate fibroids or oligovulation), menstrual cramps and breast tenderness (mo//m/no-signs of ovulation), dyspareunia|
|Family history||Recurrent pregnancy loss, endometriosis, birth defects, premature ovarian failure|
|Surgical history||Tubal ligation, ovarian cysts, endometriosis, pelvic infections, appendectomy, D&C|
|Gynecologic history||STDs, PID, abnormal pap smears and subsequent treatment|
and allergy history
|Social history||Tobacco use, alcohol use, illicit drug use|
|Review of systems||Symptoms of thyroid disease, pelvic or abdominal pain, weight changes, hirsutism, galactorrhea|
Table: Evaluation of male partner
|General Category||Specific Points|
|Length of infertility||Coital frequency, previous fertility, previous infertility treatment|
|Childhood illnesses and injuries||Mumps, testicular injuries, undescended testes|
|Family history||Infertility history, inheritable disorders|
|Urologic surgery||Vasectomy, herniorrhaphy|
|Past medical history||Diabetes, multiple sclerosis, STDs, recent febrile illnesses|
|Environmental toxins||Heat, pesticides, industrial toxins|
and allergy history
|Sulfasalazine, cimetidine (gonadotoxic but reversible); antihypertensives, antipsychotics, antidepressants (ejaculatory dysfunction); anabolic steroids (decreased spermatogenesis)|
|Social history||Tobacco use (decreased motilily), alcohol use, illicit drug use (marijuana- decreased sperm count)|
|Review of systems||Impotence, ejaculatory dysfunction|
Every infertility evaluation should begin with a complete physical exam. When examining the female partner, it is important to document height and weight, as well as body mass index (BMI = weight in kilograms/height in meters squared). There is a clear association between weight and infertility as well as a correlation between the woman’s weight and the amount of gonadotropins needed to stimulate the ovaries. It is important to check for thyroid enlargement, nodules, or tenderness, as well as identifying excessive acne or facial hair, which may be associated with increased androgen levels. Evidence of acanthosis nigricans often indicates insulin resistance, a common finding with polycystic ovarian syndrome. Other important features to note are: a “buffalo hump” (Cushing’s syndrome); short stature, webbed neck, and shield chest (Turner’s syndrome). Finally, a complete pelvic examination is crucial during the initial visit and should include evaluation for Mullerian defects, pelvic or abdominal masses, or tenderness, cervical abnormalities, and nodularity in the cul-de-sac. One should consider performing a cervical culture as well due to the association of chlamydia cervicitis and pelvic inflammatory disease.
During the examination of the male partner, one should first evaluate height, evidence of disproportionate limb length, secondary sexual characteristics, and gy-necomastia (Klinefelter’s syndrome). The genitourinary examination should include location of the urethral meatus (hypospadias), palpating the testes for location and size, palpating bilateral vas deferens, and noting any varicocele.
The evaluation of the infertile couple often includes a panel of screening tests. This includes a cervical Pap smear, maternal blood type and Rh, antibody screening, rubella status, RPR (syphilis), varicella status, hepatitis B, and cystic fibrosis. Screening for sexually transmitted diseases is also recommended for patients at high risk, and would include hepatitis C, HIV 1 and 2, HTLV, CMV, chlamydia, and gonorrhea.
Once the initial screening tests are obtained, it is important to first document evidence of ovulation. This may be performed using basal body temperature charting (biphasic —> ovulatory), urinary luteinizing hormone surge detection kits, or serum progesterone levels (>5 ng/ml —> ovulatory). An endometrial biopsy (showing secretory phase) may also be performed, but this has limited use due to the cost and invasive nature of the test. “Luteal phase defect” is a condition in which inadequate progesterone is produced by the corpus luteum as evidenced by endometrial histological dating. This is a controversial topic when used in the evaluation of the infertile couple, and recent evidence suggests that an endometrial biopsy for histological dating does not differentiate fertile from infertile women, and thus, should not be used in the routine evaluation of infertility.
Routine laboratory tests for infertility include a prolactin level (normal <20 ng/ mL) and TSH (normal <5 mIU/mL but varies with individual laboratories). Occasionally, one will want to obtain labs for excess androgen states, such as free or total testosterone, DHEA-S, and 17-OH progesterone. A fasting glucose/insulin ratio is obtained in women with polycystic ovarian syndrome to identify insulin resistance, and a 24-hour urinary cortisol may be needed to rule out Cushing’s syndrome.
An important feature of the infertility evaluation includes ovarian reserve testing. This is often performed by obtaining a cycle day 3 (CD3) serum follicle stimulating hormone level. In general, a CD3 follicle stimulating hormone <10 mIU/mL is considered normal, where 10-15 mIU/ mL is considered the “gray zone” and a CD3 follicle stimulating hormone >15 mIU/mL is considered abnormal with diminished ovarian reserve. A CD3 estradiol is also often obtained, and if elevated, may indicate a shortened follicular phase with decreased ovarian reserve. A clomiphene challenge test is another route to evaluate ovarian reserve. It is often used in older women (>35 years) or those with shortened menstrual cycles. To perform the test, a CD3 follicle stimulating hormone is obtained. Then, clomiphene 100 mg is given orally on days 5-9. On CD10, a repeat follicle stimulating hormone level is drawn. If either the CD3 or CD10 follicle stimulating hormone level is elevated (>10 mIU/mL), the test is abnormal. There is some evidence that the sensitivity of the clomiphene challenge test is higher than a basal CD3 follicle stimulating hormone level (26% vs. 8%), although both tests are routinely used. Lastly, an antral follicle count (AFC) may be obtained using transvaginal ultra-sonography to assess the number of primordial follicles during the early follicular phase. In general, an AFC count of <4 follicles is associated with a poor ovarian response.
Tubal patency and uterine cavity contour should be evaluated prior to beginning any infertility treatment. The most widely used test is the hysterosalpingogram (HSG). This is a radiological test performed as an outpatient procedure where dye is injected into the uterus through a small catheter and is imaged as it passes through the uterine cavity and fallopian tubes. It can display evidence of uterine fibroids, polyps, and synechiae (adhesions), as well as tubal patency. A sonohysterogram is an office procedure where saline is injected into the uterus under ultrasound guidance. Although it can detect uterine cavity abnormalities, it cannot show tubal patency. A hysteroscopy/laparoscopy may also be utilized to evaluate the uterine cavity and well as tubal patency through chromotubation, but this procedure is obviously much more invasive and requires general anesthesia.
Finally, a semen analysis is required to rule out a male infertility factor. If the first semen analysis is abnormal, it should be repeated. Although normal reference values can vary between laboratories, the World Health Organization recommends the following normal reference values (Table: Semen analysis: WHO normal reference values).
Table: Semen analysis: WHO normal reference values
|Viscosity||<3 (scale 0-4)|
|Sperm concentration||>20 million/mL|
|Total sperm number||>40 million/ejaculate|
|Forward progression||>2 (scale 0-4)|
|Normal morphology||>14% normal|
|Round cells||<5 million/mL|
|Sperm agglutination||<2 (scale 0-3)|