The Effect Of Premature Luteinizing Hormone Rise On The Clinical Outcomes Of Fresh GnRH-antagonist Cycles Among Normal Responders

Objectives:Premature luteinizing hormone（LH）surge,defined as the concomitant occurrence of LH rise and elevated progesterone（P）levels before follicular maturation,has been inversely related to the outcomes of fresh in vitro fertilization–embryo transfer（IVF-ET）cycles.However,there remain conflicting opinions regarding the effect of premature LH rise without progesterone elevation on fresh IVF-ET cycle outcomes.This study aims to investigate the effects of premature LH rise on pregnancy outcomes among normal responders who used flexible GnRH-ant protocol followed by fresh embryo transfer and to compare the baseline data and cycle characteristics of patients with and without premature LH rise.Materials and Methods:This retrospective cohort study included1659 patients with normal ovarian response using GnRH-ant flexible protocol and fresh embryo transfer from February 2012 to September 2021in the Department of Reproductive Medicine of the Second Hospital of Hebei Medical University.Patients were allocated into the premature LH rise group（n=196）and the control group（n=1463）according to the occurrence of serum LH level>10IU/L before or on the day of GnRH-ant initiation.Univariate and multivariate logistic regression models were established to compare the biochemical pregnancy rate,clinical pregnancy rate and embryo implantation rate between the two groups.Furthermore,stratified analysis was performed based on the P levels on trigger day.Results:Patients with premature LH rise had statistically significantly lower body mass index（BMI）,total Gn dose and total Gn duration,but statictically significantly higher basal LH levels and E₂ levels on GnRH-ant initiation day than those without premature LH rise.Patients who experienced a premature rise in LH were with significantly lower biochemical pregnancy rate（OR=0.71,95%CI（0.52,0.97）,P=0.0336）,clinical pregnancy rate（OR=0.69,95%CI（0.51,0.95）,P=0.0237）and embryo implantation rate（OR=0.75,95%CI（0.57,0.99）,P=0.0430）compared with the control group after adjusting for age,BMI,infertility duration,endometrial thickness on trigger day and the number of transferred embryos,suggesting that early LH elevation is an independent risk factor for poor IVF-ET prognosis.Further stratified analysis based on serum P level on trigger day showed that when P level was lower than1.0ng/m L,there were no statistically significant differences in biochemical pregnancy rate,clinical pregnancy rate and embryo implantation rate between the premature LH rise group and the control group,suggesting that the adverse effects of premature LH rise on IVF-ET outcomes were mainly mediated by moderately increased progesterone.Conclusions:In patients with normal ovarian response using GnRH-ant flexible protocol and fresh embryo transfer,the effect of premature LH rise on pregnancy outcome mainly depends on the progesterone level on trigger day.When serum LH>10IU/L occurs before or on the day of GnRH-ant initiation and progesterone>1.0ng/ml occurs on the day of trigger,cancellation of fresh embryo transfer should be recommended to avoid the adverse effects of high levels of LH and P on endometrial receptivity and IVF-ET outcomes.