Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics

Objective: To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. Design: Prospective observational study. Setting: National Center for Infertility Research at Michigan. Patient(s): Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women. Intervention(s): Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. Main outcome measure(s): Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E₂, P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. Result(s): Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 ± .51 vs. 4.03 ± .33 [mIU/mL ± SEM]; FSH: 5.81 ± .63 vs. 3.80 ± .45) but were not different at any other phase of the cycle. Conclusion(s): These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.