Low Serum LH Levels During Ovarian Stimulation With GnRH Antagonist Protocol Decrease the Live Birth Rate After Fresh Embryo Transfers but Have No Impact in Freeze-All Cycles.

Yiyang Luo,Shan Liu,Yuting Wan,Lin Hua,Huanhuan Li,Yuan Li,Minghui Liu,Hui Su,Haiying Ren

doi:10.3389/fendo.2021.640047

Yiyang Luo, Shan Liu + Show 7 more

Open Access

https://doi.org/10.3389/fendo.2021.640047

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Abstract

ObjectiveTo explore the association between serum LH levels and the cumulative live birth rate (CLBR) within one complete cycle, and the impact of serum LH levels on the live birth rate (LBR) after the initial embryo transfer (ET) considering different ET strategies (fresh or freeze-all).DesignA retrospective cohort study.SettingUniversity-affiliated reproductive center.Patients1480 normogonadotrophic women who underwent COS with GnRH antagonist protocol for the first IVF/ICSI attempt.Intervention(s)The sample was stratified into low and higher LH groups according to serum LH peak levels of <4 (Group A) and ≥4 IU/L (Group B) during COS. Patients were also sub-grouped into conventional fresh/frozen ET cycles and freeze-all cycles.Main outcome measure(s)The LBR after the initial embryo transfer and the CLBR within one complete cycle.Secondary outcome measure(s)The numbers of day-3 high-quality embryos, the numbers of embryos available, and the other pregnancy outcomes after the initial ET.Result(s)In the whole cohort, the CLBRs decreased significantly in the low (63.1% vs. 68.3%, P=.034) LH group compared to the higher LH group. Subgroup analysis revealed that patients with low LH levels had lower LBR after fresh ET (38.0% vs. 51.5%, P=.005) but comparable LBR after the first frozen-thawed ET (FET) in freeze-all cycles (49.8% vs. 51.8%, P=.517) than patients with higher LH peak levels. Likewise, patients with low LH levels had lower CLBR for conventional fresh/frozen ET cycles (54.8% vs. 66.1%, P=.015) but comparable CLBR for the freeze-all cycles (66.8% vs. 69.2%, P=.414) than those with higher LH levels. Following confounder adjustment, multivariable regression analyses showed that low LH level was an independent risk factor for the CLBR in the whole cohort (odds ratio (OR): 0.756, 95% confidence interval (CI): 0.604-0.965, P=.014) and in patients who underwent the conventional ET strategy (OR: 0.596, 95% CI: 0.408-0.917, P=.017). Moreover, the adverse impact of low LH levels on LBRs maintained statistically significant after fresh transfers (OR: 0.532, 95% CI: 0.353-0.800, P=.002) but not after the first FETs in freeze-all cycles (OR: 0.918, 95% CI: 0.711-1.183, P=.508).Conclusion(s)In comparison with higher LH levels, low LH levels decrease the CLBRs per oocyte retrieval cycle for normogonadotrophic women who underwent COS using GnRH antagonists. This discrepancy may arise due to the significant detrimental effect of low LH levels on the LBRs after fresh embryo transfers.

Highlights

The gonadotropin-releasing hormone (GnRH) antagonist protocol has already been one of the mainstream controlled ovarian stimulation (COS) protocols because of its convenience, safety, and comparable efficacy compared with the classical GnRH agonist long protocol [1]
Comparisons between groups did not reveal any significant differences in body mass index (BMI), antral follicle count (AFC), baseline FSH levels, type and duration of infertility, or IVF treatment indications
The present study assessed the association between serum Luteinizing hormone (LH) levels and the cumulative live birth rates (CLBRs) per oocyte retrieval cycle and live birth rates (LBRs) after the initial embryo transfer (ET) in reproductive-aged normogonadotrophic women in GnRH antagonist IVF/ICSI cycles, in consideration of different ET strategies, for the first time

Summary

Introduction

The gonadotropin-releasing hormone (GnRH) antagonist protocol has already been one of the mainstream controlled ovarian stimulation (COS) protocols because of its convenience, safety, and comparable efficacy compared with the classical GnRH agonist long protocol [1]. Various endogenous LH levels can be induced by different administration times or doses of GnRH antagonists in IVF/ICSI cycles [2,3,4]. LH levels and variations in GnRH antagonist stimulation cycles present individual differences [5, 6]. The optimal range of LH in COS is not yet well understood, and debates focused on the predictive value of LH levels for treatment outcomes never cease. Heterogeneity is prevalent in the existing studies, such as in the stimulation protocol, patient characteristics, day of LH measurement, and cut-off values for LH [11,12,13,14,15,16,17]

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