Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

Abstract Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

摘要
目的：探讨既往接受重组促卵泡激素（recombinant follicle stimulating hormone, rFSH）促排卵周期的患者，在后续周期中联合使用重组促卵泡激素（rFSH）与重组促黄体生成素（recombinant luteinizing hormone, rLH）进行促排卵治疗是否可改善妊娠结局。
方法：本项回顾性病例对照研究纳入2015年至2018年间某体外受精（in vitro fertilization, IVF）中心收治的114例患者共计228个卵胞浆内单精子注射（intracytoplasmic sperm injection, ICSI）周期，对所有病例进行回顾性分析。首次ICSI周期采用重组促卵泡激素（rFSH，商品名Gonal-f，瑞士雪兰诺公司，日内瓦，瑞士）实施控制性卵巢刺激（controlled ovarian stimulation, COS），设为rFSH组；第二次周期采用重组促卵泡激素联合重组促黄体生成素（rFSH + rLH，商品名Pergoveris，意大利巴里市默克雪兰诺股份公司）进行促排卵，设为rFSH + rLH组。比较两组患者的ICSI临床结局。
结果：相较于rFSH组，rFSH + rLH组患者的雌二醇水平、获卵数、第3天优质胚胎率及着床率均显著升高，流产率显著降低。在年龄＜35岁的患者中，rFSH + rLH组的着床率显著高于rFSH组；在年龄≥35岁的患者中，rFSH + rLH组的雌二醇水平、获卵数、第3天优质胚胎率及着床率均显著升高。在获卵数≤4枚的患者中，rFSH + rLH组的获卵数、成熟卵母细胞率、正常卵裂速率、着床率及流产率均得到改善；在获卵数≥5枚的患者中，rFSH + rLH组的雌二醇水平、获卵数及着床率均显著升高。
结论：相较于既往仅使用rFSH促排卵的周期，添加促黄体生成素（luteinizing hormone, LH）的卵巢刺激方案可提高着床率，且该效果不受产妇年龄及对控制性卵巢刺激（COS）的反应影响。按年龄及获卵数进行分层分析后，ICSI临床结局及流产率亦得到改善。