Reproductive Medicine Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Clinical Research Center For Women's Reproductive Health In Hunan Province, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Arch Gynecol Obstet. 2021 Feb;303(2):347-362. doi: 10.1007/s00404-020-05894-8. Epub 2020 Nov 24.
Patients with a poor ovarian response (POR) represent the most difficult group of population to deal with in the clinical fertility practice. Bologna criteria are the first uniform definition of POR. Choosing a suitable controlled ovarian stimulation (COS) protocol which could give adequate oocytes to maximize the chance of obtaining at least one euploid blastocyst is crucial in the management for such patients. The delayed start antagonist protocol is a novel COS protocol designed for POR patients, however, its real efficacy is controversial compared to conventional protocols. The present study aims to summarize all available studies on this topic and perform a meta-analysis to explore the real treatment effect of this novel protocol in terms of reproductive outcomes.
PubMed, EMBASE, Google Scholar, and the Cochrane Library from database establishment to June 2019 were searched. Randomized controlled trials (RCTs), which compared delayed start antagonist protocol (Del) to conventional controlled ovarian stimulation (COS) protocols (Con) in terms of reproductive outcomes, were included. The RevMan 5.3 was used to perform statistical analysis. The primary outcomes were the cycle cancellation rate, the clinical pregnancy rate and the miscarriage rate.
5 RCTs yielding 514 patients were eligible, of which 5, 5, 4 studies were included in analyzing the cycle cancellation rate, the clinical pregnancy rate, and the miscarriage rate respectively. Synthesized data of meta-analysis showed: delayed start antagonist protocol introduced a lower risk of cycle cancellation [risk ratio (RR) = 0.63, 95% confidence interval (CI) (0.45, 0.90), P = 0.01; 5 RCTs, 514 women (Del:Con = 256:258); I = 0%; with rates of 16.02% (Del) vs. 26.36% (Con)], an increased chance to get clinical pregnancy [RR = 2.30, 95% CI (1.38, 3.82), P = 0.001; 5 RCTs, 514 women (Del:Con = 256:258); I = 0%; with rates of 16.80% (Del) vs. 7.36% (Con)], and a comparable miscarriage rate [RR = 0.55, 95% CI (0.24, 1.23), P = 0.15; 4 RCTs, 58 women (Del:Con = 41:17) I = 17%; with rates of 19.51% (Del) vs. 35.29% (Con)] compared to conventional COS protocols.
Delayed start antagonist protocol was a potentially valuable alternation for poor ovarian responders. However, future RCTs with large sample size and more scientific design are needed to verify its validity and draw a sound conclusion.
卵巢反应不良（POR）的患者是临床生育实践中最难处理的人群。博洛尼亚标准是 POR 的第一个统一定义。选择合适的控制性卵巢刺激（COS）方案，该方案可以提供足够的卵子，最大限度地提高获得至少一个整倍体囊胚的机会，这对于此类患者的治疗至关重要。延迟启动拮抗剂方案是一种专为 POR 患者设计的新型 COS 方案，然而，与传统方案相比，其实际疗效存在争议。本研究旨在总结该主题的所有可用研究，并进行荟萃分析，以探讨该新型方案在生殖结局方面的真实治疗效果。
从数据库建立到 2019 年 6 月，检索了 PubMed、EMBASE、Google Scholar 和 Cochrane 图书馆。纳入了比较延迟启动拮抗剂方案（Del）与传统控制性卵巢刺激（COS）方案（Con）在生殖结局方面的随机对照试验（RCT）。使用 RevMan 5.3 进行统计分析。主要结局是周期取消率、临床妊娠率和流产率。
符合条件的 5 项 RCT 共纳入 514 名患者，其中 5 项、5 项和 4 项研究分别纳入分析周期取消率、临床妊娠率和流产率。荟萃分析的综合数据表明：延迟启动拮抗剂方案降低了周期取消的风险[风险比（RR）=0.63，95%置信区间（CI）（0.45，0.90），P=0.01；5 项 RCT，514 名女性（Del：Con=256：258）；I=0%；发生率为 16.02%（Del）与 26.36%（Con）]，增加了获得临床妊娠的机会[RR=2.30，95%CI（1.38，3.82），P=0.001；5 项 RCT，514 名女性（Del：Con=256：258）；I=0%；发生率为 16.80%（Del）与 7.36%（Con）]，流产率相当[RR=0.55，95%CI（0.24，1.23），P=0.15；4 项 RCT，58 名女性（Del：Con=41：17）I=17%；发生率为 19.51%（Del）与 35.29%（Con）]与传统的 COS 方案相比。
延迟启动拮抗剂方案可能是一种有价值的卵巢反应不良患者的治疗选择。然而，需要更多大样本量和更科学设计的 RCT 来验证其有效性并得出可靠的结论。
