A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.

IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Bei Xu, Dirk Geerts, Jiaying Yuan, Mengting Wang, Zhou Li, Qiaohong Lai, Yu Zheng, Si Liu, Shulin Yang, Guijin Zhu, Lei Jin
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引用次数: 0

Abstract

Study question: Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response?

Summary answer: The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle.

What is known already: Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon.

Study design, size, duration: An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio.

Participants/materials, setting, methods: Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation.

Main results and the role of chance: Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05).

Limitations, reasons for caution: A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings.

Wider implications of the findings: The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders.

Study funding/competing interest(s): This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest.

Trial registration number: The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.

Trial registration date: 21 November 2021.

Date of first patient’s enrollment: 23 November 2021.

采用拮抗剂提前停用和促性腺激素逐步减少方法的改良灵活 GnRH 拮抗剂方案可提高新鲜周期的活产率:随机对照试验。
研究问题:在促性腺激素释放激素(GnRH)拮抗剂方案中使用促性腺激素(Gn)降阶法,并在卵巢反应正常的患者施用 hCG 当日(hCG 日)停止使用 GnRH 拮抗剂,能否提高新鲜选择性单胚胎移植(eSET)后的妊娠结局?使用 Gn 降阶梯方法和在 hCG 日停止 GnRH 拮抗剂的改良 GnRH 拮抗剂方案可有效提高每个新鲜 eSET 周期的活产率(LBR):目前,关于最佳的 GnRH 拮抗剂方案尚未达成共识。研究表明,与长GnRH激动剂(GnRHa)方案相比,新鲜GnRH拮抗剂周期的妊娠结局较差。子宫内膜接受能力是导致这一现象的关键因素:2021年11月至2022年8月期间进行了一项开放标签随机对照试验(RCT)。共有546名患者按1:1的比例被分配到改良GnRH拮抗剂或传统拮抗剂方案中:试管婴儿和卵胞浆内单精子显微注射周期均包括在内,所使用的精子样本为来自伴侣的新鲜或冷冻精子,或来自冷冻捐献者射精的精子。主要结果是每个新鲜 SET 周期的 LBRs。次要结果包括植入率、临床和持续妊娠率、流产率、卵巢过度刺激综合征(OHSS)以及卵巢刺激的临床结果:两个卵巢刺激组的基线人口学特征无明显差异。然而,在意向治疗(ITT)人群中,改良拮抗剂组的LBR显著高于常规组(38.1% [104/273] vs. 27.5% [75/273],相对风险1.39 [95% CI, 1.09-1.77],P = 0.008)。按方案(PP)分析包括所有接受胚胎移植的患者,改良拮抗剂组的 LBR 也明显高于常规组(48.6% [103/212] vs. 36.8% [74/201],相对风险 1.32 [95% CI, 1.05-1.66],P = 0.016)。在ITT和PP分析中,改良拮抗剂组的植入率、临床妊娠率和持续妊娠率均显著高于常规组(P 0.05):我们研究的一个局限性是,在 RCT 试验中,受试者对治疗分配没有盲法。只有预后良好的 40 岁以下女性被纳入分析。因此,在卵巢储备功能低下的老年患者中使用改良拮抗剂方案仍有待研究。此外,第 5 天选择性 SET 的样本量较小,因此需要更大规模的试验来加强这些研究结果:研究经费/竞争权益:采用Gn阶梯式下降方法和在hCG日停止使用GnRH拮抗剂的改良GnRH拮抗剂方案提高了正常反应者每个新鲜eSET周期的LBRs:本项目由国家重点研发计划项目 2022YFC2702503 和北京健康促进会项目 2021140 资助。作者声明无利益冲突:该 RCT 已在中国临床试验注册中心注册;研究编号:ChiCTR2100053453:ChiCTR2100053453.试验注册日期:2021年11月21日.首例患者入组日期:2021年11月23日.
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来源期刊
Human reproduction
Human reproduction 医学-妇产科学
CiteScore
10.90
自引率
6.60%
发文量
1369
审稿时长
1 months
期刊介绍: Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues. Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.
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