Pulsatile gonadotropin-releasing hormone therapy: comparison of efficacy between functional hypothalamic amenorrhea and congenital hypogonadotropic hypogonadism

Objective: To compare the ongoing pregnancy rate per initiated cycle between patients with functional hypothalamic amenorrhea (FHA) and patients with congenital hypogonadotropic hypogonadism (CHH) treated with pulsatile gonadotropin-releasing hormone (GnRH) administration.

Design: Retrospective monocentric cohort study conducted at the University Hospital of Lille from 2004 to 2022.

Setting: Lille University Hospital, Department of Endocrine Gynecology.

Patient(s): A total of 141 patients diagnosed with central suprapituitary amenorrhea during infertility evaluation and subsequently treated with pulsatile GnRH therapy. 111 and 30 patients were diagnosed with FHA or CHH, respectively.

Intervention(s): Pulsatile GnRH administration.

Main outcome measure(s): Ongoing pregnancy rate per initiated cycle.

Result(s): Ongoing pregnancy rates per initiated cycle were comparable between groups: 21.5% in the FHA group vs. 22% in the CHH group. Comparison of baseline characteristics showed a more pronounced follicle-stimulating hormone (FSH) deficiency in patients with CHH than in those with FHA: 2.55 (0.6-4.92) vs. 4.80 (3.90-5.70) UI/L. Within the CHH group, basal FSH level was positively associated with the occurrence of ongoing pregnancies (odds ratio, 1.57; 95% confidence interval, 1.11-2.22). In the CHH group, the duration of treatment was higher than in the FHA group: 23.59 (± 8.02) vs. 18.16 (± 7.66) days.

Conclusion(s): The baseline FSH level is lower in patients with CHH than in patients with FHA. The lower the FSH, the lower the chance of pregnancy in patients with CHH. These patients also require more days of GnRH administration. However, the rate of ongoing pregnancies is comparable between the two groups.