Abstract：
OBJECTIVE: 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?
CONCLUSIONS: 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.
BACKGROUND: 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.
METHODS: 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.
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.
RESULTS: 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).
CONCLUSIONS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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.
BACKGROUND: The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
UNASSIGNED: 21 November 2021.
UNASSIGNED: 23 November 2021.
CONCLUSIONS: 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.
BACKGROUND: 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.
METHODS: 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.
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.
RESULTS: 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).
CONCLUSIONS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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.
BACKGROUND: The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
UNASSIGNED: 21 November 2021.
UNASSIGNED: 23 November 2021.
摘要：
目的：使用促性腺激素释放激素（GnRH）拮抗剂方案进行新的选择性单胚胎移植（eSET）后的妊娠结局是否可以增加使用促性腺激素（Gn）降压方法，并在卵巢反应正常的患者在hCG给药当天（hCG日）停止GnRH拮抗剂后的妊娠结局？
背景：目前，对于最佳GnRH拮抗剂方案尚无共识.研究表明，新鲜的GnRH拮抗剂周期导致比长GnRH激动剂（GnRHa）方案更差的妊娠结局。子宫内膜容受性是促成这一现象的关键因素。
方法：2021年11月至2022年8月进行了一项开放标签随机对照试验（RCT）。有546名患者以1：1的比例分配给改良的GnRH拮抗剂或常规拮抗剂方案。
方法：包括IVF和ICSI周期，使用的精子样本是新鲜的或冷冻的，或者来自冷冻的捐献者射精.主要结果是每个新鲜SET周期的LBR。次要结果包括植入率，临床和持续怀孕，流产,和卵巢过度刺激综合征（OHSS），以及卵巢刺激的临床结果。
结果：基线人口统计学特征在两个卵巢刺激组之间没有显著差异。然而,在意向治疗(ITT)人群中，改良拮抗剂组的LBRs明显高于常规组(38.1%[104/273]vs.27.5%[75/273]，相对风险1.39[95%CI，1.09-1.77]，P=0.008)。使用符合方案（PP）分析，其中包括所有接受胚胎移植的患者，改良拮抗剂组的LBRs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)。改良拮抗剂组的植入率明显较高，在ITT和PP分析中，临床和持续妊娠率均优于常规组（P<0.05）。两组取卵数或成熟卵母细胞数差异无统计学意义，双前核合子(2PN)率，获得的胚胎数量，胚泡进展和优质胚胎率，早期流产率，或OHSS发生率(P>0.05)。
结论：我们研究的一个局限性是受试者对RCT试验中的治疗分配不了解。只有40岁以下预后良好的女性才被纳入分析。因此,改良拮抗剂方案在卵巢储备低的老年患者中的应用仍有待研究.此外,第5天选修集的样本量很小，因此，将需要更大的试验来加强这些发现。
结论：使用Gn降压方法和在hCG日停止GnRH拮抗剂的改良GnRH拮抗剂方案改善了正常反应者每个新的eSET周期的LBR。
背景：本项目由国家重点研发计划2022YFC2702503和北京市健康促进会2021140资助。作者声明没有利益冲突。
背景：RCT已在中国临床试验注册中心注册；研究编号：ChiCTR2100053453。
■2021年11月21日。
■2021年11月23日。
背景：目前，对于最佳GnRH拮抗剂方案尚无共识.研究表明，新鲜的GnRH拮抗剂周期导致比长GnRH激动剂（GnRHa）方案更差的妊娠结局。子宫内膜容受性是促成这一现象的关键因素。
方法：2021年11月至2022年8月进行了一项开放标签随机对照试验（RCT）。有546名患者以1：1的比例分配给改良的GnRH拮抗剂或常规拮抗剂方案。
方法：包括IVF和ICSI周期，使用的精子样本是新鲜的或冷冻的，或者来自冷冻的捐献者射精.主要结果是每个新鲜SET周期的LBR。次要结果包括植入率，临床和持续怀孕，流产,和卵巢过度刺激综合征（OHSS），以及卵巢刺激的临床结果。
结果：基线人口统计学特征在两个卵巢刺激组之间没有显著差异。然而,在意向治疗(ITT)人群中，改良拮抗剂组的LBRs明显高于常规组(38.1%[104/273]vs.27.5%[75/273]，相对风险1.39[95%CI，1.09-1.77]，P=0.008)。使用符合方案（PP）分析，其中包括所有接受胚胎移植的患者，改良拮抗剂组的LBRs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)。改良拮抗剂组的植入率明显较高，在ITT和PP分析中，临床和持续妊娠率均优于常规组（P<0.05）。两组取卵数或成熟卵母细胞数差异无统计学意义，双前核合子(2PN)率，获得的胚胎数量，胚泡进展和优质胚胎率，早期流产率，或OHSS发生率(P>0.05)。
结论：我们研究的一个局限性是受试者对RCT试验中的治疗分配不了解。只有40岁以下预后良好的女性才被纳入分析。因此,改良拮抗剂方案在卵巢储备低的老年患者中的应用仍有待研究.此外,第5天选修集的样本量很小，因此，将需要更大的试验来加强这些发现。
结论：使用Gn降压方法和在hCG日停止GnRH拮抗剂的改良GnRH拮抗剂方案改善了正常反应者每个新的eSET周期的LBR。
背景：本项目由国家重点研发计划2022YFC2702503和北京市健康促进会2021140资助。作者声明没有利益冲突。
背景：RCT已在中国临床试验注册中心注册；研究编号：ChiCTR2100053453。
■2021年11月21日。
■2021年11月23日。
