Fertility 101 (Part 2)

 Last month we addressed the basic infertility work-up.  This article will discuss specific causes and their evaluation.

Male Factor

The male factor is estimated to be significant in 40%-50% of couples.  To determine the adequacy of the spermatozoa, the man must submit a semen sample for analysis after at least 2, but no more than 5 days of sexual abstinence.  Sperm morphology has shown to be the most important semen parameter in predicting fertility rates and pregnancy outcome in assisted reproduction.  Abnormal semen parameters can result from fluctuations in hormonal levels, from genetic or congenital abnormalities, and from drug use, infections, previous surgery, and exposure to occupational and environmental toxins.

Ovulation and Luteal Phase

Ovulatory dysfunction occurs in approximately 30% of infertile patients.  Presumptive evidence of ovulation is determined by using the basal body temperature (BBT) chart, steroid or gonadotropin hormone assays, and ultrasound; by analyzing cervical mucus changes; or by an endometrial biopsy.  A history of regular monthly menses, premenstrual molimina, and dysmenorrhea are usually indicative of ovulation.  The mid-cycle luteinizing hormone (LH) surge is the most reliable predictor or ovulation, but its analysis requires frequent blood sampling and expensive radioimmunoassay.  The determination of BBT is the oldest and most widely used test, but it is not the most accurate or reliable method of ovulation detection.  Temperature elevation is secondary to the effect of progesterone on the hypothalamus.  A temperature greater than 98 degrees Fahrenheit with a rise of 0.4-0.6 degrees Fahrenheit between 2 consecutive days is characteristic of ovulation.  The BBT predicts the LH surge within 2-3 days.  A sustained elevation of temperature for less than 10 days suggests a luteal phase deficieny (LPD).  A single serum progesterone reading of greater than 3 ng/mL in the luteal phase is presumptive evidence of ovulation, and greater than 10 ng/mL virtually excludes a LPD.

The endometrial biopsy is another method of confirming ovulation but also evaluates the adequacy of the luteal phase.  This test is the histologic means to diagnose a luteal-phase defect (LPD), however the clinical significance of LPD is highly dubious.  More recently, the lack of alpha v beta 3 integrin expressed by the endometrium has been associated with a decreased rate of implantation.  This protein is only expressed during the window of implantation and its absence is found in 50% of patients with endometriosis.

Tubal and Uterine Factor

Tubal factor infertility, a cause in 30%-50% of cases, may first be suspected on the basis of the patient’s history.  Significant risk factors include a history of acute salpingitis (often referred to as pelvic inflammatory disease [PID]), septic abortion, ruptured appendix, pelvic or tubal surgery, a history of an ectopic pregnancy, and possibly use of an intrauterine device.  The incidence of infertility after salpingitis is 11%-12%, 23%, and 54% for one, two, and, at least, three episodes, respectively.  In addition, salpingitis increases the risk for ectopic pregnancy due to damage of the tubal mucosa.  Nevertheless, about half of the patients with tubal disease or pelvic adhesions have a negative history for PID.  Hydrosalpinges have been demonstrated to have a deleterious effect on implantation either from retrograde toxic fluid or absence of integrin.  Salpingectomy (removing the tube) or salpingostomy (opening the tube) has been recommended to improve pregnancy rates naturally or with assisted reproduction.

The uterine factor is a rare cause of infertility, accounting for only about 2% of cases.  Anatomic causes such as leiomyomas, polyps or, rarely, adhesions can impair sperm transport or embryo implantation.