Zhang Dan, Xia Lan, Xu Huihui, Chen Qian, Jin Bailing, Zhang Aijun, Xu Bufang
Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Reproductive Medicine, Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2018 Dec 19;9:767. doi: 10.3389/fendo.2018.00767. eCollection 2018.
Gonadotropin-releasing hormone antagonist (GnRH-ant) has been shown to negatively influence endometrial receptivity. Reducing the GnRH-ant dose during controlled ovarian stimulation (COS) when using a GnRH-ant protocol may be beneficial to embryo implantation. However, whether or not the minimum daily GnRH-ant dose should be individualized remains uncertain. In this retrospective study, we aimed to elucidate the feasibility and effectiveness of moderately reducing the daily GnRH-ant dose to 0.125 mg, and then adjusting the dose to 0.25 mg based on subsequent luteinizing hormone (LH) levels. Of the 434 patients analyzed in this study, 209 received our new flexible low-dose GnRH-ant protocol (Group 1) and 225 received a conventional GnRH-ant protocol with a fixed daily dose of 0.25 mg (Group 2). Furthermore, 105 and 114 cycles from groups 1 and 2 received fresh embryo transfer. In Group 1, 30 patients whose dose of 0.125 mg GnRH-ant was adjusted according to their LH levels and 179 patients who received consistently low doses were further divided into subgroups 1 and 2, respectively. Neither the number of retrieved oocytes and available embryos nor the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate significantly differed between the two groups. However, GnRH-ant dose and stimulation duration were much lower and shorter in Group 1 than in Group 2 ( < 0.05). Subgroup 1 exhibited higher basal follicle-stimulating hormone (FSH) and lower antral follicle count (AFC) than subgroup 2 significantly. The number of retrieved oocytes and available embryos were lower in subgroup 1 than in subgroup 2 (6.83 ± 3.28 vs. 11.83 ± 4.82, 2.93 ± 1.86 vs. 4.99 ± 3.46, respectively, < 0.05), while more canceled cycles for pre-ovulation occurred in subgroup 1 than in subgroup 2 (3/30 vs. 1/179, < 0.05). The results showed that the flexible low-dose GnRH-ant protocol was as effective as the conventional fixed-dose GnRH-ant protocol with 0.25 mg per day for most patients with normal ovarian reserve. This retrospective analysis and the small sample size are the main limitations of this study, and a large sample RCT will be carried out in the future.
促性腺激素释放激素拮抗剂（GnRH-ant）已被证明会对子宫内膜容受性产生负面影响。在使用GnRH-ant方案进行控制性卵巢刺激（COS）期间降低GnRH-ant剂量可能有利于胚胎着床。然而，每日GnRH-ant的最小剂量是否应个体化仍不确定。在这项回顾性研究中，我们旨在阐明将每日GnRH-ant剂量适度降低至0.125mg，然后根据随后的黄体生成素（LH）水平将剂量调整至0.25mg的可行性和有效性。在本研究分析的434例患者中，209例接受了我们新的灵活低剂量GnRH-ant方案（第1组），225例接受了每日固定剂量0.25mg的传统GnRH-ant方案（第2组）。此外，第1组和第2组分别有105个和114个周期接受了新鲜胚胎移植。在第1组中，30例根据LH水平调整GnRH-ant剂量至0.125mg的患者和179例持续接受低剂量的患者分别进一步分为亚组1和亚组2。两组之间的获卵数、可用胚胎数、着床率、临床妊娠率和持续妊娠率均无显著差异。然而，第1组的GnRH-ant剂量和刺激持续时间明显低于和短于第2组（<0.05）。亚组1的基础促卵泡激素（FSH）水平高于亚组2，窦卵泡计数（AFC）低于亚组2，差异有统计学意义。亚组1的获卵数和可用胚胎数低于亚组2（分别为6.83±3.28 vs. 11.83±4.82，2.93±1.86 vs. 4.99±3.46，<0.05），而亚组1排卵前取消周期的发生率高于亚组2（3/30 vs. 1/179，<0.05）。结果表明，对于大多数卵巢储备正常的患者，灵活低剂量GnRH-ant方案与每日0.25mg的传统固定剂量GnRH-ant方案效果相同。本回顾性分析和小样本量是本研究的主要局限性，未来将开展大样本随机对照试验。
