OBJECTIVE To study the impact of both controlled ovarian hyperstimulation (COH) length and total gonadotropin (GN) dose individually and in concert on live birth rates (LBR) in both fresh and freeze-all in vitro fertilization embryo transfer (IVF-ET) cycles. DESIGN Historical cohort study. SETTING Not applicable. PATIENT(S) The U.S. national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2015 was used to identify patients undergoing autologous GN stimulation IVF cycles with the use of GnRH antagonist-based suppression protocols where a single embryo transfer was performed as part of a fresh IVF-ET cycle (fresh, n = 14,866) or the first frozen embryo transfer after a freeze-all cycle (frozen, n = 2,964), and not including preimplantation genetic testing cycles. The patients' demographic and cycle characteristics, duration of COH, total GN dose, and pregnancy outcomes were extracted. Binomial regression models estimated trend and relative risk of live birth with respect to days of stimulation and total GN dose singularly, and after adjustment for a priori confounders including age, parity, body mass index, diagnosis, and maximum follicle-stimulating hormone in both fresh and frozen embryo transfer cycles. Both days of stimulation and total GN dose were then added to the multivariate model to show whether they were independently associated with LBR. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Live birth rate. RESULTS In both fresh and frozen cycles, length of COH was significantly associated with total GN dose. On univariate analysis, LBR decreased significantly with increasing length of stimulation and increasing total GN dose in both fresh and frozen cycles. On multivariable analysis including both days of stimulation and total GN dose, days of stimulation was no longer significantly correlated with LBR, whereas total GN dose remained significantly correlated with LBR in fresh cycles only. When total GN doses ranging from <2,000 IU through 5,000 IU to >5,000 IU were compared, a significant improvement in live birth rate was noted with lower total GN doses. Specifically, GN doses <2,000 IU had a 27% higher rate of live birth compared with GN dose >5,000 IU. For GN dose groups up to 4,000 IU, the estimated effect on LBR was similar. There was a marginal improvement (13%) in LBR with GN doses of 4,000 IU to 5,000 IU compared with >5,000 IU. When the multivariate model was applied to the frozen cycles, neither total GN dose nor days of stimulation was significantly associated with LBR. CONCLUSIONS High total GN dose but not prolonged COH is associated with decreasing LBRs in fresh cycles, whereas neither factor significantly affects LBR in frozen cycles. Consideration should be given to minimizing the total GN dose when possible in fresh autologous cycles, either by decreasing the daily dose or by limiting the length of stimulation to improve LBRs. In freeze-all cycles, the use of higher GN doses does not seem to adversely affect the LBR of the first frozen embryo transfer. High total GN dose likely exerts a negative impact on the endometrium and/or oocyte/embryo unrelated to the length of stimulation. The differential effect of total GN dose on LBR in fresh and frozen cycles may imply a greater impact exerted on the endometrium rather than the oocyte.

中文翻译：

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在新鲜和冷冻胚胎移植周期中受控卵巢过度刺激对活产率的不同影响：辅助生殖技术协会临床结果系统研究

目的 研究单独控制的卵巢过度刺激 (COH) 长度和总促性腺激素 (GN) 剂量对新鲜和全冷冻体外受精胚胎移植 (IVF-ET) 周期中活产率 (LBR) 的影响. 设计 历史队列研究。设置 不适用。患者 2014 年至 2015 年辅助生殖技术协会临床结果报告系统的美国国家数据库用于识别使用基于 GnRH 拮抗剂的抑制方案进行自体 GN 刺激 IVF 周期的患者，其中单胚胎移植是作为新鲜 IVF-ET 周期（新鲜，n = 14,866）或全部冷冻周期（冷冻，n = 2,964）后第一次冷冻胚胎移植的一部分进行，不包括植入前基因检测周期。患者的 提取人口统计学和周期特征、COH 持续时间、总 GN 剂量和妊娠结局。二项回归模型根据刺激天数和总 GN 剂量单独估计活产的趋势和相对风险，并在调整了包括年龄、胎次、体重指数、诊断和最大卵泡刺激素在内的先验混杂因素后和冷冻胚胎移植周期。然后将刺激天数和总 GN 剂量添加到多变量模型中，以显示它们是否与 LBR 独立相关。干预措施 不适用。主要结果测量活产率。结果 在新鲜和冷冻周期中，COH 的长度与总 GN 剂量显着相关。在单变量分析中，在新鲜和冷冻周期中，随着刺激时间的增加和总 GN 剂量的增加，LBR 显着降低。在包括刺激天数和总 GN 剂量在内的多变量分析中，刺激天数不再与 LBR 显着相关，而总 GN 剂量仅在新鲜周期中仍与 LBR 显着相关。当 GN 总剂量范围从 <2,000 IU 到 5,000 IU 到 >5,000 IU 进行比较时，发现总 GN 剂量较低时活产率显着提高。具体而言，与 GN 剂量 >5,000 IU 相比，GN 剂量 <2,000 IU 的活产率高 27%。对于高达 4,000 IU 的 GN 剂量组，对 LBR 的估计影响相似。GN 剂量从 4,000 IU 到 5,000 IU 与 > 5,000 IU 相比，LBR 略有改善（13%）。当多变量模型应用于冷冻周期时，总 GN 剂量和刺激天数都与 LBR 没有显着关联。结论 高总 GN 剂量但不延长 COH 与新鲜周期中 LBR 的降低相关，而这两个因素均不显着影响冷冻周期中的 LBR。在新的自体循环中，应考虑尽可能减少总 GN 剂量，方法是减少每日剂量或限制刺激时间以改善 LBR。在全冷冻周期中，使用更高的 GN 剂量似乎不会对第一次冷冻胚胎移植的 LBR 产生不利影响。高总 GN 剂量可能会对子宫内膜和/或卵母细胞/胚胎产生与刺激时间无关的负面影响。