Diagnostic Tests

When evaluating an infertile couple, diagnostic studies should be selected as indicated. If the history is unclear, then tests that address the above-mentioned major categories of infertility should be obtained.

Male factor testing

After a medical history and physical examination, semen analysis is the single best test for evaluating for male factor infertility.

For optimum and consistent results, abstinence is required 3-5 days prior to semen collection. The World Health Organization (WHO) has established methods for semen analysis, but methods may vary among facilities. Additionally, the WHO has established normal reference values.

Another commonly used method for evaluating morphology is the strict Kruger method. Although no particular measurements can be used to discriminate between fertile and infertile men, odds of male infertility increase with increases in the number of semen parameter abnormalities.

• Volume - At least 2 mL or greater
• Sperm concentration - 20 million/mL or more
• Motility - At least 50% or more with forward progression
• Morphology - At least 30% or more normal forms (14% strict Kruger criteria)
• White blood cells - Fewer than 1 million/mL
• Round cells - Fewer than 5 million/mL

Ovulatory function testing

Women of reproductive age who have regular menstrual cycles lasting from 21-35 days are likely ovulatory. However, for patients to become more accustomed to predicting ovulation so that they can appropriately time intercourse, they may wish to initiate basal body temperature monitoring or use luteinizing hormone (LH) detection kits.

Basal body temperature (BBT) monitoring is largely a historical method for determining the correct timing of intercourse. A 0.5–1.0ºF rise in temperature is noted 2 days after the luteinizing hormone (LH) peak, which occurs after the day of ovulation. This results from progesterone production from the corpus luteum. This should be done with a special mercury thermometer before rising from bed. Since most studies show that the best day to introduce sperm into the female reproductive tract is either the day of ovulation or the day before ovulation, BBT monitoring -is not useful for coital timing in a current cycle but best serves as a method to confirm the time of ovulation and helps the patient to predict future cycles based on data she has gathered over prior cycles. This method is inexpensive but time-consuming and cumbersome. Urine LH kits are a more useful method to prospectively predict the day of ovulation; however, they can be expensive and result in confusing results, particularly in the setting of the use of clomiphene citrate, patients with oligo-ovulation, or if pregnancy has occurred.

A deficiency in progesterone production by the corpus luteum (CL) has historically been attributed to infertility and recurrent pregnancy loss in many women with otherwise unexplained miscarriages. The significance and presence of an inadequate luteal phase (also referred to as luteal phase defect [LPD]) has been questioned throughout the literature. Traditionally, diagnosis of an LPD has been determined histologically (a lag of >2 days of an endometrial biopsy compared with the day of the cycle, based on the actual day of ovulation). Some physicians prefer to use low luteal phase progesterone levels (<10 ng/mL) 6 days after ovulation as their method of diagnosis, with good correlation to histologic findings if repeated in 3 separate menstrual cycles. Isolated LPD (by histological criteria) are observed in 30-40% of healthy fertile couples as well as infertile couples, implying that this defect must be a repetitive event to be a true cause of infertility or miscarriage. 

Ovarian reserve testing

Several simple tests for ovarian reserve exist. Initial testing usually includes cycle day 3 laboratories including follicle stimulating hormone (FSH), estradiol (E2), and leuteinizing hormone (LH).Typically, if the FSH level is greater than 15 mIU/mL or the estradiol level is greater than 75 pg/mL, the prognosis is poor. Day 3 antral follicle scans and ovarian volume may also be used to evaluate ovarian reserve and are simple and accurate.

In patients older than 40 years or for whom poor ovarian reserve is suspected, a clomiphene citrate challenge test may be performed. Clomiphene citrate (100 mg PO qd) is administered on cycle days 5-9. FSH and estradiol levels are drawn on days 3 and 10. If the day-3 or day-10 FSH level is greater than 15 mIU/mL or the day-3 estradiol level is greater than 75 pg/mL, the test results are considered abnormal. The rationale is that if the woman has an elevated day-10 estradiol level due to the clomiphene, yet her FSH level is not suppressed (estrogen suppresses FSH by a negative feedback mechanism), she has significant decreased ovarian reserve.

Tubal disease testing

In patients with unremarkable history or examination findings, a hysterosalpingogram (HSG) performed 2-5 days after the cessation of menstrual flow is the procedure of choice to evaluate tubal anatomy and patency. The risk of infection is extremely low, and most patients do not require antibiotic prophylaxis unless the patient has a history of pelvic infection. Additionally, if distal tubal occlusion is found, treatment should be provided because the risk of infection increases and treatment has been show to prevent infection in these cases. The HSG is a radiographic technique in which a dye is injected into the cervix. This dye fills the uterus and eventually the tubes. If the tubes are patent, dye spills out into the abdominal cavity. The test requires approximately 10 minutes to complete. This procedure is primarily diagnostic, but it may possibly be therapeutic (for approximately 6 mo). Additionally, it provides imaging of the uterine cavity.

A history of pelvic inflammatory disease, septic abortion, ruptured appendix, tubal surgery, or ectopic pregnancy should alert the physician to the possibility of tubal damage. In these patients or in patients with significant pelvic pain during the physical examination, proceeding to a diagnostic laparoscopy rather than an HSG may be prudent given the probability of pelvic pathology. In this case, the tubes and the rest of the pelvis may be directly inspected and a chromopertubation may be performed. During this procedure, dye is injected through the cervix and into the uterus. If the dye is seen to spill from both of the tubal openings, the fallopian tubes are presumed patent.

Cervical disease testing

Women who have had cervical cone biopsies or trauma to the cervix are at risk for cervical abnormalities and cervical stenosis. If a cervical abnormality is found, the most logical approach is to recommend bypassing the cervix with intrauterine inseminations (IUI), especially if the rest of the findings from the infertility evaluation are normal.

In the past, suspected cervical factor infertility was tested with a postcoital test (PCT), looking at the interaction of cervical mucous and sperm at a specified time after intercourse during the perio-ovulatory phase of the cycle. This is often considered unnecessary today with the use of the IUI.

Uterine disease testing

Similar to tubal disease, obtaining a history from the patient is the most important diagnostic tool. A history of repetitive abortions, uterine surgery, postpartum uterine infections, retained products of conception, or postpartum curettage should alert the clinician to a possible uterine factor. A history of abnormal bleeding, such as heavy menses, midcycle spotting, or irregular bleeding, may represent an intrauterine fibroid, polyp, or synechiae. Malpresentation during pregnancy or recurrent pregnancy loss often suggests a uterine anomaly, such as a septum or bicornuate uterus.

A screening transvaginal ultrasonography performed immediately following the cessation of menses may demonstrate a uterine leiomyoma (fibroid) or an endometrial polyp. A sonohysterogram (SHG) or HSG which can also evaluate the fallopian tubes can also be used to better evaluate the uterine cavity.

If the patient has known blocked tubes and is scheduled for in vitro fertilization (IVF), a sonohysterogram (SHG) or office hysteroscopy (HSC) may be performed. An SHG is performed by placing a small catheter in the uterine cavity and instilling sterile saline to separate the endometrial walls under ultrasonographic guidance. SHG is more sensitive than an HSG in delineating fibroids and polyps. HSC allows for direct visualization of the cavity via an optic fiber.

Testing for endocrine abnormalities

Any evidence of the following should warrant selective hormonal studies.

• Hirsutism or hair loss
• Abnormal weight gain
• Oily skin or acne
• Purple striae on the abdomen
• Polyuria/polydipsia
• Irregular menses
• Heat or cold intolerance
• Headaches, visual problems or lactation without prior pregnancy

If the patient displays hirsutism, with or without menstrual irregularity, the patient may have polycystic ovarian disease. Especially if there is a family history of diabetes then a glucose tolerance test should be obtained. If unusual weight gain or fatigue develops, a thyroid-stimulating hormone (TSH) should be obtained. If galactorrhea or irregular menses occurs, measuring the prolactin level should be considered.