A 32-year-old never having been pregnant woman presents to our office with her husband for infertility evaluation. They have been trying to conceive for 12 months without success, despite having intercourse 2 to 3 times per week. They have not sought infertility treatment until now because they are concerned about the cost of care.
Diagnostic evaluation for causes of infertility is indicated after 12 months of regular unprotected intercourse when the female partner is under 35 and after 6 months if the female partner is 35 or older. 85 to 90 percent of apparently normal couples will conceive in the first 12 months. Infertility evaluation is warranted earlier if the couple suffers conditions known to limit fertility such as advanced endometriosis problems, oligomenorrhea or amenorrhea, known or suspected uterine or tubal disease, or suspected male subfertility. Evaluation and treatment should occur immediately in women over 40.
Ovulatory dysfunction is one of the most common findings in infertile women; therefore, ovulatory status needs to be assessed in each patient. Often, a thorough menstrual history is all that is needed. A patient with monthly menses and moliminal symptoms is considered ovulatory, while those with amenorrhea or oligomenorrhea are unlikely to be ovulating regularly. For those patients in whom ovulatory status is unclear, further testing would be indicated. A simple option is to obtain a midluteal progesterone. This should be scheduled for a week prior to anticipated menses, which would be dependent on the individual patient’s cycle length. A progesterone level >3 ng/mL indicates ovulation. Another option is to have the patient use an ovulation predictor kit. It is important to stress to the couple that the color change indicates the luteinizing hormone (LH) surge, which precedes ovulation by 24-48 hours. Intercourse is recommended the day of the LH surge or the following day.
Ovulatory dysfunction, if identified, warrants further investigation to determine a possible etiology and guide treatment. It is similarly important to identify a structured and basic evaluation of oligomenorrhea (<9 cycles/year) or amenorrhea. A TSH and prolactin should be obtained to rule out thyroid disorders and hyperprolactinemia. If these were normal, it would be reasonable to order a serum follicle-stimulating hormone (FSH), particularly if there is concern for primary ovarian insufficiency. Polycystic ovarian syndrome (PCOS) is often considered in this evaluation and should be further investigated, especially if the patient reports symptoms of hyperandrogenism such as hirsutism and acne.
It is estimated that approximately 25-35 percent of couples suffer male factor infertility. Formal recommendations are for a complete medical history of the male partner and at least one semen analysis. There is a great deal of intra-individual variation in the test, and a repeat semen analysis to confirm an abnormality can be useful. As the provider ordering the semen analysis, one should counsel the male partner that the test should be performed after 2-5 days of abstinence. Ideally, the specimen is collected by masturbation at the laboratory in which the testing is performed. Despite its inherent limitations, many providers consider semen analysis an important step prior to moving forward with the treatment of the female partner, given the relatively high prevalence of male factor infertility. On the other hand, couples in which the male partner is healthy, is without risk factors, and has fathered a child in the past may choose to forgo semen analysis initially.
Testing for tubal patency is also a conventional part of an initial infertility evaluation. The most commonly performed test is the HSG due to it being both diagnostic and possibly therapeutic, as there is evidence of increased pregnancy rates following HSG. In addition to showing both proximal and distal tubal occlusion, HSG can detect salpingitis isthmica nodosa (SIN) and intracavitary abnormalities, such as submucosal fibroids and Müllerian anomalies, which can affect fertility.
Often, if the HSG is abnormal, such as a pelvic ultrasound to assess fibroids, a 3D pelvic ultrasound or MRI to further characterize a Müllerian anomaly, or even laparoscopy. In a patient in whom laparoscopy is planned, a chromopertubation can be performed at the time of surgery, obviating the need for HSG. In this case, in the absence of risk factors, it is possible that this test would be of limited value. It may be appropriate to address a finding of ovulatory dysfunction initially and proceed with HSG if the subfertility persists.
The American Society for Reproductive Medicine (ASRM) suggest ovarian reserve testing on women over the age of 35 who present for fertility evaluation as well as others with increased risk of decreased reserve, such as those with a history of cancer or medical problems treated with gonadotoxic therapy, surgery to the ovaries, or pelvic radiation. It is inferred that ovarian reserve testing should not be performed as initial screening in all patients who present with inability to conceive. There are multiple tests for decreased ovarian reserve. The most appropriate initial tests are a basal (“day 3”) FSH and Estradiol. Elevated FSH of 10-20 IU/L is associated with poor response to ovarian stimulation. Estradiol is often added to the FSH to confirm the value of the FSH. An elevated estradiol (>80pg/mL) can suppress a rising FSH and result in a false negative FSH if it is evaluated alone. An alternative ovarian reserve test is a single measure of the anti- Müllerian hormone (AMH), which reflects the size of the primordial follicle pool. The benefit of this test is that it can be drawn at any time during the menstrual cycle as it has shown little inter-cycle and intra-cycle variability. Additionally, the AMH is less expensive than the FSH and Estradiol together, suggesting this may be the ideal test when cost is a concern.
Features of the history or physical exam concerning for endometriosis problems are often identified. Treatment of endometriosis problems implants with ablation or resection, even in early disease, can improve pregnancy rates. Likewise, the diagnosis of endometriosis problems will dictate infertility treatment options and is therefore important to make. While surgical evaluation should be performed in women with symptoms concerning for endometriosis problems or other pelvic/peritoneal pathology, diagnostic laparoscopy for asymptomatic women as part of a standard evaluation is of low yield and should not be a first step.
Diagnostic infertility evaluation should be performed after 12 months of inability to conceive in patients <35 years of age, after six months in patients age 35 or older or with obvious risk factors, and immediately in women over age 40,
Ovulatory status should be assessed in every patient and can frequently be done with history alone. Further laboratory testing should be dictated by these findings,
Semen analysis, HSG, and ovarian reserve testing can be performed in a stepwise fashion, targeting the most likely potential etiologies identified on history and physical exam first, with further workup only if infertility persists,
Ovarian reserve testing need not be performed on every patient but limited to those >35 years or with significant risk factors for decreased ovarian reserve,
Diagnostic laparoscopy may be indicated for patients in whom endometriosis problems or other peritoneal pathology is suggested by history or exam, but should not be performed on all patients.