拮抗剂方案下波塞冬4组患者不同时机添加人重组黄体生成素的临床效果

Comparison of clinical outcomes of different recombinant LH supplementation in POSEIDON group 4 patients under GnRH antagonist protocol

目的 探讨拮抗剂方案中不同时机添加重组人黄体生成素(rLH)在波塞冬4组患者体外受精/卵胞浆内单精子注射(IVF/ICSI)周期中的临床效果。方法 回顾性分析2017年1月至2022年12月在我中心行拮抗剂方案促排卵并符合波塞冬4组诊断标准的卵巢低反应(POR)患者的临床资料,按照是否添加rLH和添加时机分为4组:对照组(促排卵过程中未添加rLH,n=481)、早卵泡期添加组[在促性腺激素(Gn)启动日添加rLH,n=116]、拮抗剂日添加组(拮抗剂添加日添加rLH,n=100)和晚卵泡期添加组(Gn使用8 d后添加rLH,n=82),比较各组患者的一般情况、促排卵情况、胚胎发育情况和鲜胚移植临床妊娠结局。结果 (1)一般情况:各组间患者年龄、不孕年限、既往IVF/ICSI治疗周期数和不孕类型比较均无显著性差异(P>0.05)。(2)促排卵情况:与对照组比较,早卵泡期添加组Gn刺激天数、Gn总量均显著减少(P<0.05),而晚卵泡期添加组的Gn刺激天数和Gn总量均显著增加(P<0.01),拮抗剂日添加组Gn刺激天数显著减少(P<0.05);拮抗剂日添加组E2水平显著高于对照组(P<0.05),早卵泡期添加组HCG日≥18 mm卵泡数显著高于对照组(P<0.05),早卵泡期添加组和拮抗剂日添加组HCG日内膜厚度均显著高于对照组(P<0.05)。(3)胚胎发育情况:在IVF和ICSI周期中,早卵泡期添加组获卵数、2PN数、2PN卵裂数、D3优胚数和可利用胚胎数均显著高于对照组(P<0.05);在IVF周期中,拮抗剂日添加组获卵数、2PN数和2PN卵裂数均显著高于对照组(P<0.05)。(4)妊娠结局:早卵泡期、拮抗剂日和晚卵泡期添加组鲜胚移植率均显著高于对照组(P<0.05);早卵泡期和拮抗剂日添加组周期取消率显著低于对照组(P<0.05)。结论 对于高龄、卵巢低储备的POR患者,早卵泡期添加rLH可获得更多的卵母细胞、第3天优质胚胎和可利用胚胎,降低周期取消率,获得更多的移植机会。

Objective:To analyze the clinical effects of recombinant human luteinizing hormone(rLH)supplementation in IVF/ICSI among POSEIDON group 4 patients under the GnRH antagonist protocol.Methods:Data of 779 patients,who met the criteria of POSEIDON group 4 as poor ovarian response(POR)and underwent controlled ovarian hyperstimulation by GnRH antagonist protocol in Reproductive Medicine Center of People’s Hospital of Wuhan University from January 2017 to December 2022 were retrospectively analyzed.According to the different rLH supplementation,the included participants were divided into four groups:control group(no rLH supplementation,n=481),early follicular phase supplementation group(rLH supplementation initiating on the first day of stimulation,n=116),GnRH antagonist day supplementation group(rLH supplementation initiating on GnRH antagonist day,n=100),and late follicular phase supplementation group(rLH supplementation initiating after eight days of stimulation,n=82).The basic characteristics,controlled ovarian stimulation,embryonic development and pregnancy outcomes of fresh embryo transfer cycles were compared among the four groups.Results:As for the baseline characteristics,no significant differences were found in age,infertility years,previous cycle number of IVF/ICSI treatment,and infertility types among the four groups(P>0.05).Regarding controlled ovarian stimulation,the gonadotropin(Gn)stimulation days and total Gn dosage were significantly lower in early follicular phase supplementation group,but significantly higher in late follicular phase supplementation group(P<0.05)than that in the control group(P<0.05).The duration of Gn stimulation was remarkably decreased in GnRH antagonist day supplementation group when compared with the control group(P<0.05).The estradiol(E 2)level on trigger day was significantly increased in GnRH antagonist day supplementation group when compared with the control group(P<0.05),and the number of dominant follicles not less than 18 mm was higher in early follicular phase supplementation group(P<0.05),and the endometrium thicknesses were lower in both early follicular phase and GnRH antagonist day supplementation groups(P<0.05).As for embryonic laboratory outcomes,the numbers of retrieved oocyte,two pronuclei(2PN)oocyte,2PN cleavage rate,high-quality embryo on day 3,and available embryos in early follicular phase supplementation group were remarkably higher than those in the control group(P<0.05)in both IVF and ICSI cycles.In IVF cycles,the numbers of retrieved oocyte,2PN oocyte and 2 PN cleavage rate in GnRH antagonist day supplementation group were significantly higher than those of the control group(P<0.05).The fresh embryo transfer rate was remarkably higher in early follicular phase,GnRH antagonist day,and late follicular phase supplementation groups than that in control group(P<0.05),and the cycle cancellation rate was significantly lower in early follicular phase and GnRH antagonist day supplementation groups than that of the control group(P<0.05).Conclusions:For POR women with advanced maternal age and diminished ovarian reserve,early follicular phase supplementation of rLH can increase the numbers of retrieved oocyte,high-quality embryo on day 3,and available embryos,with declined cycle cancellation rate and more opportunities of embryo transfer.