卵巢储备功能正常人群卵泡期GnRH-a长方案不同时期添加尿促性腺激素对临床结局的影响

Effects of menotrophin supplementation at different stages on clinical outcome of patients with normal ovarian response after treatment with GnRH agonist long protocol in follicular phase

目的探讨卵巢储备功能正常患者在卵泡期GnRH激动剂(GnRH-a)长方案中不同时机添加高纯度尿促性腺激素(Hp-HMG)对临床结局的影响。方法回顾性分析2019年4月至2021年12月在我院生殖中心行IVF/ICSI-ET助孕的462例卵巢储备功能正常患者的484个周期临床资料,均采用卵泡期GnRH-a长方案促排卵。根据方案中添加Hp-HMG(外源性LH类似物,含FSH、LH各75 U/支)时机不同分为两组:早卵泡期开始全程添加Hp-HMG为早加组(n=332);晚卵泡期即控制性卵巢刺激(COS)的第6~8天添加Hp-HMG为晚加组(n=152)。比较两组患者的一般资料、促排卵结局及临床妊娠结局。结果(1)两组间年龄、不孕年限、基础FSH、LH、PRL、孕酮、雄激素水平、抗苗勒管激素(AMH)水平和基础窦卵泡数(AFC)比较均无显著差异(P>0.05);早加组血清基础雌二醇(E 2)水平显著低于晚加组(P<0.05),体质量指数(BMI)显著高于晚加组(P<0.05)。(2)GnRH-a降调节后,两组间促性腺激素(Gn)启动日血清FSH、LH及E 2水平,HCG日血清LH、E 2水平和内膜厚度比较均无显著差异(P>0.05);早加组Gn起始剂量略高于晚加组但无统计学差异(P>0.05),早加组Gn天数、Gn总量显著高于晚加组(P<0.05),而HCG日孕酮水平显著低于晚加组(P<0.05)。(3)两组间平均获卵数、MⅡ卵数、2PN数、D3可利用胚胎数、优胚率、胚胎着床率、临床妊娠率比较均无显著差异(P>0.05)。(4)多重线性回归分析显示,Hp-HMG添加时机与血清孕酮水平显著相关(P<0.05)。结论卵巢储备功能正常患者在卵泡期GnRH-a长方案不同时机补充Hp-HMG不影响临床结局,但早卵泡期添加Hp-HMG有利于HCG日孕酮保持较低水平。

Objective:To investigate the impact of applying highly purified menotrophin(Hp-HMG)at different stages on pregnancy outcomes in patients with normal ovarian reserve after treatment with GnRH agonist(GnRH-a)long protocol in follicular phase.Methods:The clinical data of 484 normal ovarian reserve patients who underwent IVF/ICSI-ET with GnRH-a long protocol in follicular phase from Apr.2019 to Dec.2021 in Reproductive center of our hospital were retrospectively analyzed.According to the stage of the use of Hp-HMG(exogenous LH analog,containing 75 U/amp of FSH and LH respectively),the patients were divided into two groups:Hp-HMG was added in the early follicular phase in early addition Hp-HMG group(n=332)and Hp-HMG was added in the sixth to eighth day of menstrual cycle in late addition Hp-HMG group(n=152).The general information,ovulation induction outcome and pregnancy outcomes were compared between the two groups.Results:There were no significance differences in age,duration of infertility,basic level of FSH,LH,PRL,progesterone,testosterone,AMH and antral follicle count(AFC)between the two groups(P>0.05).The basic E 2 level in early addition Hp-HMG group was significantly lower than that in late addition Hp-HMG group(P<0.05),and the body mass index(BMI)was significantly higher(P<0.05).There were no significantly differences in the levels of FSH,LH and E 2 levels on the gonadotropin(Gn)initial day,serum LH&E 2 levels and endometrial thickness on HCG day after GnRH-a down-regulation(P>0.05).The initial Gn doses in early addition Hp-HMG group was higher than in late addition Hp-HMG group,but there was no significantly difference(P>0.05).The total doses and days of Gn in early addition Hp-HMG group were significantly higher than those in the late addition Hp-HMG group(P<0.05),while the progesterone level on the day of HCG injection was significantly lower in early addition Hp-HMG group(P<0.05).There were no significant differences in the average number of oocytes retrieved,MⅡoocytes number,2PN number,number of Day 3 available embryos,good-quality embryo rate,embryo implantation rate and clinical pregnancy rate between the two groups(P>0.05).The progesterone level on the day of HCG were positively correlated with the timing of the use of Hp-HMG by multiple linear regression.Conclusions:The supplement of exogenous LH in follicular phase may not influence the clinical outcomes in patient with normal ovarian response after treatment with GnRH-a long protocol in follicular phase.However,Hp-HMG supplementation at early follicular stage is beneficial to maintain a low level of progesterone on HCG day.