Anovulatory Patients Demonstrate a Sharp Decline in LH Levels upon GnRH Antagonist Administration during IVF Cycles.

Linoy Segal,Ofer Fainaru,Shahar Kol

doi:10.5041/rmmj.10298

Abstract

To evaluate the decrease in luteinizing hormone (LH) levels following gonadotropin-releasing hormone (GnRH) antagonist administration in in vitro fertilization (IVF) cycles, data were retrospectively collected from 305 consecutive IVF or intracytoplasmic sperm injection (ICSI) cycles of patients who underwent ovarian stimulation with gonadotropins and were treated with GnRH antagonist for the prevention of premature luteinization. We compared the percent change in LH concentration from stimulation start to that observed before ovulation triggering in patients with or without anovulation. Anovulatory patients were younger, with higher body mass index (BMI), and demonstrated higher ovarian reserve parameters as compared to ovulatory patients. The decline in LH concentration was almost two-fold greater in anovulatory versus ovulatory patients. Numbers of oocytes, fertilizations, cleavage stage embryos, and transferred embryos were similar; however, implantation rates were higher in anovulatory versus ovulatory patients. Older patients (age ≥39) showed a smaller decline in LH levels as compared to younger ones (age <39) and exhibited poor IVF outcomes. There is a wide range of pituitary responses to GnRH antagonists. Anovulatory patients are more susceptible to GnRH antagonists and therefore demonstrate over-suppression of the pituitary. Older patients demonstrate a reduced pituitary response to GnRH antagonists than younger ones. Cycle scheduling with estradiol pretreatment did not influence LH decline, nor IVF treatment outcomes.

Highlights

Gonadotropin-releasing hormone (GnRH) antagonists have been used with success in in vitro fertilization (IVF) clinics as of the late 1990s, but the ideal luteinizing hormone (LH) serum level in patients undergoing IVF is still under debate
In a previous study we demonstrated that 26% of patients stimulated with recombinant folliclestimulating hormone (FSH), receiving only 0.25 mg of GnRH antagonists, displayed “over-suppression” (LH level 24 hours after GnRH antagonist injection
Hormone levels (LH, progesterone, and estradiol) on the day of stimulation start were similar between the two groups, LH levels before ovulation triggering were lower in anovulatory patients (1.8±1.2 versus 3.0±2.8 IU/L; P=0.02)

Summary

Introduction

Gonadotropin-releasing hormone (GnRH) antagonists have been used with success in in vitro fertilization (IVF) clinics as of the late 1990s, but the ideal luteinizing hormone (LH) serum level in patients undergoing IVF is still under debate. In the study by the Ganirelix dose finding study group, very low LH levels were achieved in the two highest-dose groups (1 and 2 mg), the implantation rates were significantly lower, and the miscarriage rates during the first 6 weeks after embryo transfer were relatively higher, compared to the lower doses (such as 0.25 mg daily dose).[3] Early pregnancy loss in LH-suppressed subjects was demonstrated in normo-gonadotropic women treated with GnRH agonists.[4] Huirne et al showed the potential role of changes in LH levels during the cycle, rather than absolute levels. In their study pregnancies were not achieved when the change in LH level was either too great or too small, paralleling excessive or insufficient suppression of LH secretion.[5]

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