Association between GnRH Receptor Polymorphisms and Luteinizing Hormone Levels for Low Ovarian Reserve Infertile Women.

Shun-Long Weng,Tsung-Hsien Lee,Chun-Chia Huang,Chun-I Lee,Chung-Hsien Liu,Shu-Ling Tzeng,Maw-Sheng Lee,Shun-Fa Yang

doi:10.3390/ijerph18137006

Abstract

The choice of ovarian stimulation protocols in assisted reproduction technology (ART) cycles for low ovarian reserve patients is challenging. Our previous report indicated that the gonadotrophin-releasing (GnRH) agonist (GnRHa) protocol is better than the GnRH antagonist (GnRHant) protocol for young age poor responders. Here, we recruited 269 patients with anti-Müllerian hormone (AMH) < 1.2 ng/mL undergoing their first ART cycles for this nested case-control study. We investigated the genetic variants of the relevant genes, including follicular stimulating hormone receptor (FSHR; rs6166), AMH (rs10407022), GnRH (rs6185), and GnRH receptor (GnRHR; rs3756159) in patients <35 years (n = 86) and patients ≥35 years of age (n = 183). Only the genotype of GnRHR (rs3756159) is distributed differently in young (CC 39.5%, CT/TT 60.5%) versus advanced (CC 24.0%, CT/TT 76.0%) age groups (recessive model, p = 0.0091). Furthermore, the baseline luteinizing hormone (LH) levels (3.60 (2.45 to 5.40) vs. 4.40 (2.91 to 6.48)) are different between CC and CT/TT genotype of GnRHR (rs3756159). In conclusion, the genetic variants of GnRHR (rs3756159) could modulate the release of LH in the pituitary gland and might then affect the outcome of ovarian stimulation by GnRHant or GnRHa protocols for patients with low AMH levels.

Highlights

In assisted reproduction technology (ART) for infertile couples, management for patients with an inadequate ovarian response is challenging [1,2,3,4]
Most reports recommended the protocol for the use of gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) or the mild stimulation protocol (MSP) for the poor responders, instead of the long protocol for using GnRH agonist (GnRHa) [9]
We previously reported a better pregnancy outcome by the GnRHa than the GnRH antagonist (GnRHant) protocol in POSEIDON group 3 patients [10]

Summary

Introduction

In assisted reproduction technology (ART) for infertile couples, management for patients with an inadequate ovarian response is challenging [1,2,3,4]. Investigators propose two international definitions, the Bologna [5] and POSEIDON [6] criteria, for poor responders, the choice of ovarian stimulation protocols for these patients is still controversial [7,8]. Most reports recommended the protocol for the use of gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) or the mild stimulation protocol (MSP) for the poor responders, instead of the long protocol for using GnRH agonist (GnRHa) [9]. The primary reason for this recommendation is the cost-effective consideration, which is adjusted by the cost per oocyte retrieved and the number of exogenous gonadotropin injections. Because it remains controversial, the GnRHa protocol is less recommended for poor responders.

Methods

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Discussion

Conclusion