High ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in a GnRH-antagonist protocol
High ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in a GnRH-antagonist protocol
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DOI：
10.1093/humrep/des389
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发表时间：
2013-02-01
影响因子：
6.1
通讯作者：
Mannaerts, Bernadette
中科院分区：
文献类型：
--
作者：
Fatemi, Human M.;Doody, Kevin;Mannaerts, Bernadette
当考虑到影响新鲜胚胎移植后妊娠概率的主要协变量时，卵巢对控制性卵巢刺激（COS）的反应是否与持续妊娠率相关？在GnRH拮抗剂方案中接受促皮质素α或每日重组FSH（rFSH）治疗的患者中，高卵巢反应并不影响持续妊娠率，也不影响新鲜和冷冻后累积妊娠率的增加，已经描述了卵母细胞数量和妊娠率之间的强相关性，但这是第一个评估可能影响妊娠率的重要混杂因素的综合分析。在一项大型、前瞻性、双盲、随机试验（Engage; n 1506）中，患者在促性腺激素释放激素拮抗剂（加尼瑞克）方案中，在COS的前7天接受单剂量150 g皮质促卵泡素α或每日200 IU rFSH治疗。在这项回顾性分析中，根据获得的卵母细胞数量将患者分为5组（05、69、1013、1418和18个卵母细胞）。评价了各组获得和移植的优质胚胎数量，以及每个开始周期的持续妊娠率、活产率和累积持续妊娠率。进行单变量分析，以确定预测继续妊娠机会的因素。按治疗组（皮质促卵泡素α和rFSH）和总体分别对因变量持续妊娠和累积持续妊娠（包括卵母细胞类别作为模型中的独立因素）进行Logistic回归分析。考虑到卵巢反应以及其他确定的成功的重要预测因素，对持续妊娠和累积持续妊娠的可能性进行评估。总共有1506例患者以1：1的比例随机分配到两个治疗组。患者年龄为36岁，体重60 kg。皮质促卵泡素α组和rFSH组每个起始周期的持续妊娠率分别从最低应答组（0.5个卵母细胞）的31.9和31.3增加至最高应答组（18个卵母细胞）的41.9和43.4，具有显著线性趋势（P 0.04）。在Corifollitropin α和rFSH组中，考虑冻融胚胎移植的累积妊娠率分别从33.0和31.3增加到60.8和55.9。持续妊娠的单变量logistic回归分析显示以下因素具有显著影响：胚胎移植（双侧或单侧，P 0.01），治疗区域（北美或欧洲，P 0.01），hCG当天的孕酮水平（1.5或1.5 ng/ml，P 0.01）、刺激开始日（周期第2或3天，P 0.02）和年龄（P 0.04）。使用1013个卵母细胞作为参考类别，对每个治疗组和总体的持续妊娠进行Logistic回归分析，显示相对于参考的估计比值比（OR）接近1.0，在调整和不调整影响妊娠率的显著预测因素的情况下，无统计学显著差异。累积妊娠的未校正OR反映了与参考相比，最低应答组的妊娠几率显著较低，最高应答组的妊娠几率显著较高。当对预测因素进行调整时，累积持续妊娠或最高应答组与参考组的平均水平（95置信区间）为1.87（1.342.59）当合并两个治疗组的数据时。最终模型中包含的协变量数量限于五个主要因素，并非所有其他潜在的显著预测因素均可用于评估。仅限于36岁以下月经周期规律、体重60和90 kg的IVF患者，接受GnRH拮抗剂方案治疗，不能外推至其他患者人群或治疗方案。默克公司（Merck Co. Inc）的子公司，位于美国新泽西州怀特豪斯站。医学写作和编辑协助由P.米尔纳博士（PAREXEL，UK）提供。这项援助是由默克公司，夏普多梅公司，默克公司的子公司，新泽西州怀特豪斯站。作者的利益冲突如下：H.F.曾因与MSD举行专家会议、为多家公司举办讲座而获得酬金;已收到Ferring和TEVA Pharmaceutical的咨询费，Ferring和沃森Pharmaceutical的讲座和发言人办公室的付款; G. G.作为演讲者获得酬金，并担任Ferring，Merck Serono，MSD和IBSA的顾问委员会成员。他获得了默克雪兰诺、默沙东的旅行赠款，以及辉凌和默克雪兰诺的赠款;和B.M.之间。是MSD.NTC00696800的员工。
Is the ovarian response to controlled ovarian stimulation (COS) related to the ongoing pregnancy rate when taking into account the main covariates affecting the probabilities of pregnancy following fresh embryo transfer?In patients treated with corifollitropin alfa or daily recombinant FSH (rFSH) in a GnRH-antagonist protocol, a high ovarian response did not compromise ongoing pregnancy rates and increased cumulative pregnancy rates following fresh and frozen-thawed embryo transfer.A strong association between the number of oocytes and pregnancy rates has been described but this is the first comprehensive analysis assessing important confounders that might affect pregnancy rates.In a large, prospective, double-blind, randomized trial (Engage; n 1506), patients were treated with either a single dose of 150 g corifollitropin alfa or daily 200 IU rFSH for the first 7 days of COS in a GnRH-antagonist (ganirelix) protocol. In this retrospective analysis, patients were categorized into five groups according to the number of oocytes retrieved (05, 69, 1013, 1418 and 18 oocytes). The number of good-quality embryos obtained and transferred, as well as the ongoing pregnancy rates, live birth rates and cumulative ongoing pregnancy rates per started cycle by group were evaluated. Univariate analysis was performed to identify factors that predict the chance of ongoing pregnancy. Logistic regression analysis on the dependent variables ongoing pregnancy and cumulative ongoing pregnancy, respectively, including oocyte category as an independent factor in the model, was performed by treatment group (corifollitropin alfa and rFSH) and overall. The likelihood of ongoing pregnancy and cumulative ongoing pregnancy was then evaluated taking into account ovarian response as well as other identified significant predictors of success.In total, 1506 patients had been randomized in a ratio of 1:1 to either of the treatment groups. Patients were aged 36 years and had a body weight 60 kg.The ongoing pregnancy rates per started cycle increased in the corifollitropin alfa and rFSH groups from 31.9 and 31.3, respectively, in the lowest response group (05 oocytes) to 41.9 and 43.4 in the highest response group (18 oocytes) with a significant linear trend (P 0.04). The cumulative pregnancy rates taking frozenthawed embryo transfers into account increased from 33.0 and 31.3 to 60.8 and 55.9 in the corifollitropin alfa and rFSH groups, respectively. Univariate logistic regression analyses of ongoing pregnancy showed significant effects for the following factors: embryo transfer (double or single, P 0.01), region of treatment (North America or Europe, P 0.01), progesterone level on the day of hCG (1.5 or 1.5 ng/ml, P 0.01), start day of the stimulation (cycle day 2 or 3, P 0.02) and age (P 0.04). Logistic regression analysis of ongoing pregnancy using 1013 oocytes as the reference category, per treatment group and overall revealed estimated odds ratios (OR) close to 1.0 versus the reference, without statistically significant differences with and without adjustment for significant predictive factors affecting pregnancy rates. Unadjusted OR for cumulative pregnancy reflected significantly lower odds of pregnancy for the lowest response group and significantly higher odds of pregnancy for the highest response group in comparison with the reference. When adjusted for the predictive factors, the cumulative ongoing pregnancy OR (95 confidence interval) of the highest response group versus the reference group was 1.87 (1.342.59) when the data of both treatment groups were pooled.The number of covariates included in the final model was limited to five major factors and not all other potentially significant predictive factors were available for evaluation.This analysis is limited to IVF patients with a regular menstrual cycle up to 36 years of age and a body weight 60 and 90 kg treated with a GnRH-antagonist protocol and cannot be extrapolated to other patient populations or treatment regimens.Financial support for this study was provided by Merck, Sharp Dohme Corp., a subsidiary of Merck Co. Inc, Whitehouse Station, NJ, USA. Medical writing and editorial assistance was provided by P. Milner, PhD, of PAREXEL, UK. This assistance was funded by Merck, Sharp Dohme Corp., a subsidiary of Merck Co. Inc., Whitehouse Station, NJ. Author conflicts of interest are as follows: H.F. has received honorarium for expert meeting with MSD, lectures for various companies; K.D. has received consultancy fees for Ferring and TEVA Pharmaceutical, payment for lectures and speaker bureaus for Ferring and Watson Pharmaceutical; G.G. has received honoraria as speaker, and served as advisory board member for Ferring, Merck Serono, MSD and IBSA. He has received travel grants from Merck Serono, MSDand grants from Ferring and Merck Serono; H.W. and B.M. are employees of MSD.NTC00696800.