Handa Mika, Takiuchi Tsuyoshi, Kawaguchi Sumika, Ohara Yasuhiro, Doshida Masakazu, Takeuchi Takumi, Matsubayashi Hidehiko, Ishikawa Tomomoto, Komukai Sho, Kitamura Tetsuhisa, Kimura Tadashi
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Clinical Genomics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
PLoS One. 2025 Jan 16;20(1):e0317103. doi: 10.1371/journal.pone.0317103. eCollection 2025.
The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA (n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix (n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 (N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0-32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5-0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999-1.007) with PPOS (p = 0.194) and 1.009 (95% CI: 0.962-1.059) with GnRH-ant (p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985-1.020) with PPOS (p = 0.783) and 1.022 (95% CI: 0.839-1.246) with GnRH-ant (p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments.
在卵巢刺激方案中明智地选择排卵抑制剂对于辅助生殖技术(ART)的成功至关重要。在此,我们使用单变量和多变量泊松回归分析,研究了两种不同的排卵抑制剂醋酸氯地孕酮(CMA)和西曲瑞克对卵巢储备功能正常患者卵母细胞成熟的剂量依赖性影响。2018年3月至2020年10月期间,在我们中心纳入了在首次体外受精周期中接受含CMA的孕激素预处理卵巢刺激(PPOS)(n = 299)或含西曲瑞克的促性腺激素释放激素拮抗剂(GnRH-ant)(n = 605)的患者(N = 904)。主要和次要结局分别为卵母细胞成熟率和受精率。在调整了包括年龄、抗苗勒管激素水平、总促性腺激素剂量和扳机类型等多个协变量后,我们计算了1 mg CMA或0.25 mg西曲瑞克的剂量依赖性调整相对风险(aRR)和95%置信区间(CI)。在PPOS组中,中位年龄为34.0岁,CMA总剂量中位数为22 mg(四分位间距[IQR]:18.0 - 32.0)。在GnRH-ant组中,中位年龄为35.0岁,西曲瑞克总剂量中位数为0.5 mg(IQR 0.5 - 0.5)。PPOS组成熟率的aRR为1.003(95% CI:0.999 - 1.007)(p = 0.194),GnRH-ant组为1.009(95% CI:0.962 - 1.059)(p = 0.717)。PPOS组受精率的aRR为1.002(95% CI:0.985 - 1.020)(p = 0.783),GnRH-ant组为1.022(95% CI:0.839 - 1.246)(p = 0.829)。总体而言,这些发现表明在所应用的剂量范围内,排卵抑制剂对卵巢储备功能正常患者的卵母细胞成熟或受精率没有显著影响。这些有价值的见解可应用于设计ART方案时,并可能指导临床医生优化不孕症治疗。