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

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.

Luteinizing Hormone Suppression by Progestin-Primed Ovarian Stimulation Is Associated With Higher Implantation Rate for Patients With Polycystic Ovary Syndrome Who Underwent in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: Comparing With Short Protocol

“…In contrast, a study by Benmachiche et al (2019) reported low serum LH levels on the day of GnRH-agonist trigger were associated with reduced rates of live birth. However, a recently published study of another center reported that low serum LH levels during ovarian stimulation with GnRH antagonist protocol had no impact on the live birth rate in freeze-all cycles (Luo et al, 2021). These inconsistent studies probably resulted from the variety in the definition of low LH, measurement parameters of LH, and the clinical interventions.…”

Luteinizing hormone-based modified GnRH antagonist protocol in normal responders undergoing in vitro fertilization treatment: A multi-center randomized controlled trial

“…Besides, we found in another previous study that the cumulative live birth rate (CLBR) in the low LH group was significantly lower than in the high LH group. Patients with low LH levels had a lower live birth rate (LBR) after fresh embryo transfer but comparable LBR after the first FET in freeze-all cycles ( 19 ). On the other hand, high LH levels during the follicular phase were also associated with poor oocyte or embryo quality and impaired endometrial receptivity and, consequently, with a negative impact on reproductive outcomes ( 20 , 21 ).…”

A novel GnRH antagonist protocol based on LH levels versus traditional flexible GnRH antagonist protocol in PCOS patients undergoing in vitro fertilization: study protocol for a randomized controlled, non-inferiority trial

“…Basic and clinical evidence has indicated that a threshold of LH stimulation is required for adequate follicular development and oocyte maturation. An ultra-low level of LH would do harm to pregnancy outcomes [ 12 ]. Our previous retrospective study data indicated that LH-based protocols might improve reproductive outcomes compared with a GnRH agonist during ovarian stimulation in normal responders [ 11 ].…”