Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen, 518045, Guangdong Province, People's Republic of China.
Reprod Sci. 2021 Oct;28(10):2847-2854. doi: 10.1007/s43032-021-00538-x. Epub 2021 May 6.
This retrospective cohort study aimed to explore the optimal endometrial preparation protocols among different maternal age groups. A total of 16,867 frozen-thawed embryo transfer (FET) cycles were categorized into three groups based on endometrial preparation protocols: Natural cycle (NC n = 3893), artificial cycles (AC, n = 11456) and AC with GnRH-a pretreatment (AC+GnRH-a, n = 1518). To account for repeat cycles, a generalized estimating equation (GEE) method was applied to examine the associations between cycle regimens and pregnancy outcomes. Subgroup analyses were conducted to evaluate the best preparation methods for different maternal age groups. Primary outcomes were live birth and early miscarriage rates. After completing GEE, in overall population, the live birth rate [(NC as reference; AC: adjusted odds ratio (aOR) = 0.837, 95% confidential interval (CI) 0.771-0.908; AC+GnRHa: aOR = 0.906, 95%CI 0.795-1.031)] in NC was significantly higher than that in AC, while comparable that in AC+GnRH-a. The early miscarriage rate (AC: aOR = 1.420, 95%CI 1.225-1.646; AC+GnRHa: aOR = 1.545, 95%CI 1.236-1.931) was significantly lower in NC compared to either AC group. Subgroup analysis showed that in younger women, the incidences of live birth (AC: aOR = 0.900, 95%CI 0.804-1.007; AC+GnRHa: aOR = 1.091, 95%CI 0.904-1.317) were equivalent between groups, with a slightly higher in AC+GnRH-a. Early miscarriage rate (AC: aOR = 1.462, 95%CI 1.165-1.835; AC+GnRHa: aOR = 1.137, 95%CI 0.948-1886) was only significantly lower in NC compared to that in AC. In older women, the live birth rate (AC: aOR = 0.815, 95%CI 0.722-0.920; AC+GnRHa: aOR = 0.759, 95%CI 0.627-0.919) was significantly higher, and early miscarriage rate (AC: aOR = 1.353, 95%CI 1.118-1.638; AC+GnRHa: aOR = 1.704, 95%CI 1.273-2.280) was significantly lower in NC compared to either AC group. Our study demonstrated that NC is associated with lower early miscarriage late in overall IVF population. There is a mild favor of AC+GnRH-a in younger women, while the priority of NC is remarkable in older women. Maternal age should be a considerable factor when determining endometrial preparation method for FET.
本回顾性队列研究旨在探讨不同年龄段妇女中不同的子宫内膜准备方案的最佳选择。根据子宫内膜准备方案，将 16867 个冷冻胚胎移植（FET）周期分为三组：自然周期（NC，n=3893）、人工周期（AC，n=11456）和 GnRH-a 预处理的人工周期（AC+GnRH-a，n=1518）。为了考虑重复周期，应用广义估计方程（GEE）方法来检验周期方案与妊娠结局之间的关系。进行亚组分析以评估不同年龄段妇女的最佳准备方法。主要结局是活产率和早期流产率。完成 GEE 后，在总体人群中，NC 的活产率[（NC 作为参考；AC：调整优势比（aOR）=0.837，95%置信区间（CI）0.771-0.908；AC+GnRHa：aOR=0.906，95%CI 0.795-1.031)]明显高于 AC，而与 AC+GnRH-a 相当。NC 的早期流产率（AC：aOR=1.420，95%CI 1.225-1.646；AC+GnRHa：aOR=1.545，95%CI 1.236-1.931）明显低于 AC 组。亚组分析显示，在年轻女性中，活产率（AC：aOR=0.900，95%CI 0.804-1.007；AC+GnRHa：aOR=1.091，95%CI 0.904-1.317）两组间无差异，但 AC+GnRH-a 组略高。早期流产率（AC：aOR=1.462，95%CI 1.165-1.835；AC+GnRHa：aOR=1.137，95%CI 0.948-1886）仅在 NC 组明显低于 AC 组。在老年女性中，活产率（AC：aOR=0.815，95%CI 0.722-0.920；AC+GnRHa：aOR=0.759，95%CI 0.627-0.919）明显升高，早期流产率（AC：aOR=1.353，95%CI 1.118-1.638；AC+GnRHa：aOR=1.704，95%CI 1.273-2.280）在 NC 组明显低于 AC 组。本研究表明，NC 与 IVF 总体人群晚期的早期流产率降低有关。在年轻女性中，AC+GnRH-a 有轻微优势，而在老年女性中，NC 的优势更为显著。当确定 FET 的子宫内膜准备方法时，产妇年龄应是一个重要因素。
