Low LH Level on the Day of GnRH Agonist Trigger Is Associated With Reduced Ongoing Pregnancy and Live Birth Rates and Increased Early Miscarriage Rates Following IVF/ICSI Treatment and Fresh Embryo Transfer.

Abdelhamid Benmachiche,Peter Humaidan,Sebti Benbouhedja,Abdelali Zoghmar

doi:10.3389/fendo.2019.00639

Abstract

Objective: To examine the correlation between serum luteinizing hormone (LH) levels on the day of GnRH agonist (GnRH-a) trigger and reproductive outcomes following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh embryo transfer, and to identify a pre-trigger serum LH threshold which would be compatible with the most optimal cycle outcome.Design: This study is based on data from a previously published randomized controlled trial conducted from 2014 to 2016.Patients: A total of 322 participants were enrolled.Setting: Private IVF center. Intervention(s): GnRH-antagonist-based IVF cycles triggered with GnRH-a. For the purpose of the study, patients were stratified according to preovulatory LH quartiles (Q1-Q4). Main Outcome Measure(s): Ongoing pregnancy rates (OP), live birth rates (LB) and early pregnancy loss (EPL) rates.Results: The results of the present study showed increasing OP as well as LB rates and decreasing EPL rates with increasing pre-trigger serum LH levels (P for trend < 0.06, 0.07, and 0.02), respectively. The absolute difference between the highest LH(Q4) and the lowest LH (Q1) group was 13.4%, 12.1%, and 12% in OP, LB, and EPL rates, respectively. In multivariate regression analysis, a pre-trigger serum LH level of 1.60 mIU/ml was identified as a threshold below which reproductive outcomes decreased. The ROC curve values were statistically significant for OP, LB, and EPL; the AUC (95% CI) = [0.57 (0.50–0.63) P < 0.04; 0.57 (0.50–0.63) P < 0.05, and 0.60 (0.51–0.70) P < 0.04], respectively. A significant positive correlation was found on the day of GnRH-a trigger between serum LH, the number of follicles, serum P4, and serum E2, p < 0.03; P < 0.03; and P < 0.001, respectively.Conclusion: Low serum LH levels on the day of GnRH-a trigger is associated with reduced ongoing pregnancy and live birth rates and increased early miscarriage rates. Our findings suggest a lower threshold of serum LH values on the day of GnRH-a trigger necessary to optimize reproductive outcomes in fresh embryo transfer cycles.Clinical Trial Registration: www.ClinicalTrials.gov, Number: 02053779

Highlights

Luteinizing hormone (LH) is essential for normal folliculogenesis and oocyte maturation in the natural ovulatory menstrual cycle [1]
For the purpose of the study, patients were divided into four distinct groups according to their quartile serum LH levels on the day of GnRH agonist (GnRH-a) trigger: [Q1: < 0.68, Q2: 0.68–0.98, Q3: 0.99–1.60, and Q4: > 1.60 mIU/ml] (Figure 1)
Our findings are in accordance with a prior study [28] showing that patients with LH levels < 0.5 mIU/ml before the day of human chorionic gonadotropin (hCG) trigger in GnRH antagonist cycles exhibited an impairment of their endometrial receptivity since they had decreased implantation rates and live birth (LB) rates as compared to patients with LH levels > 0.5 mIU/ml, despite significantly higher number of oocytes retrieved and embryos obtained in the group of patients with low LH levels

Summary

Introduction

Luteinizing hormone (LH) is essential for normal folliculogenesis and oocyte maturation in the natural ovulatory menstrual cycle [1]. When GnRH agonist (GnRH-a) is used for final oocyte maturation, low LH levels will be present after the initiation of the GnRH antagonist cotreatment [9,10,11], raising concerns that LH levels may be too low for optimal cycle outcomes when FSH only is used for ovarian stimulation. It was found that low LH levels on the day of GnRH-a trigger were associated with a low mature oocyte yield [20, 21] Their impact on the probability of pregnancy is still unknown. The primary objective of the present study was to examine the relationship between serum LH levels on the day of ovulation trigger and the reproductive outcomes in patients triggered with a bolus of GnRH-a followed by a modified luteal phase support (LPS) and fresh embryo transfer. The secondary objective was to identify a pre-trigger serum LH threshold, if appropriate, which would be compatible with the most optimal cycle outcome

Methods

Results

Discussion

Conclusion