越南胡志明市医药大学Lan N Vuong团队研究了自然、改良自然或人工子宫内膜准备开始的排卵期妇女接受冷冻胚胎移植后的活产率。2024年6月26日出版的《柳叶刀》杂志发表了这项成果。

冷冻胚胎移植（FET）在体外受精（IVF）中的应用有所增加。然而，FET周期的最佳子宫内膜准备方案尚不清楚。研究组比较了FET前子宫内膜准备的自然和改良自然周期策略与人工周期策略。

在这项随机、开放标签研究中，研究组在越南胡志明市的一家医院招募了18-45岁的排卵期女性，她们被随机分配（1:1:1）到自然、改良自然或人工周期子宫内膜准备中，使用计算机生成的随机列表和分组随机化。由于研究干预措施的性质，试验没有双盲。在自然周期中，不使用雌激素、孕酮或人绒毛膜促性腺激素（hCG）。在改良的自然周期中，使用hCG来触发排卵。在人工周期中，使用口服戊酸雌二醇（从月经第2-4天开始，每天8毫克）和阴道孕酮（从子宫内膜厚度≥7毫米开始，每天800毫克）。将胚胎玻璃化，然后在超声引导下对一个或两个第三天的胚胎或一个第五天的胚胎进行加温和移植。如果第一次FET周期被取消，随后的周期用人工子宫内膜准备进行。主要终点是一次FET后的活产。

在2021年3月22日至2023年3月14日期间，研究组对4779名女性进行了筛查，1428人被随机分配（每组476人）。在自然周期组和改良周期组中各取消了99个FET首个周期，而在人工周期组中没有取消。一次FET后的活产率为174（37%），自然周期策略组为476例，改良自然周期策略组为159例（33%），人工周期策略组为162例（34%）（自然与人工周期策略的相对风险为1.07[95%CI 0.87-1.33]，改良自然与人工周期策略为0.98[0.79-1.22]）。产妇和新生儿的结局在各组之间没有显著差异，因为检测微小差异的能力很低。

研究结果表明，尽管在接受FET IVF的排卵期妇女中，采用自然、改良的自然和人工周期子宫内膜准备策略后，活产率相似，但对于这三种方法的相对安全性，还不能得出确切的结论。

附：英文原文

Title: Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial

Author: Vu N A Ho, Toan D Pham, Nam T Nguyen, Rui Wang, Robert J Norman, Ben W Mol, Tuong M Ho, Lan N Vuong

Issue&Volume: 2024-06-26

Abstract:

Background

Use of frozen embryo transfer (FET) in in-vitro fertilisation (IVF) has increased. However, the best endometrial preparation protocol for FET cycles is unclear. We compared natural and modified natural cycle strategies with an artificial cycle strategy for endometrial preparation before FET.

Methods

In this randomised, open-label study, we recruited ovulatory women aged 18–45 years at a hospital in Ho Chi Minh City, Viet Nam, who were randomly allocated (1:1:1) to natural, modified natural, or artificial cycle endometrial preparation using a computer-generated random list and block randomisation. The trial was not masked due to the nature of the study interventions. In natural cycles, no oestrogen, progesterone, or human chorionic gonadotropin (hCG) was used. In modified natural cycles, hCG was used to trigger ovulation. In artificial cycles, oral oestradiol valerate (8 mg/day from day 2–4 of menstruation) and vaginal progesterone (800 mg/day starting when endometrial thickness was ≥7 mm) were used. Embryos were vitrified, and then one or two day-3 embryos or one day-5 embryo were warmed and transferred under ultrasound guidance. If the first FET cycle was cancelled, subsequent cycles were performed with artificial endometrial preparation. The primary endpoint was livebirth after one FET. This trial is registered at ClinicalTrials.gov, NCT04804020.

Findings

Between March 22, 2021, and March 14, 2023, 4779 women were screened and 1428 were randomly assigned (476 to each group). 99 first FET cycles were cancelled in each of the natural and modified cycle groups, versus none in the artificial cycle group. The livebirth rate after one FET was 174 (37%) of 476 in the natural cycle strategy group, 159 (33%) of 476 in the modified natural cycle strategy group, and 162 (34%) of 476 in the artificial cycle strategy group (relative risk 1·07 [95% CI 0·87–1·33] for natural vs artificial cycle strategy, and 0·98 [0·79–1·22] for modified natural vs artificial cycle strategy). Maternal and neonatal outcomes did not differ significantly between groups, as the power to detect small differences was low.

Interpretation

Although the livebirth rate was similar after natural, modified natural, and artificial cycle endometrial preparation strategies in ovulatory women undergoing FET IVF, no definitive conclusions can be made regarding the comparative safety of the three approaches.

DOI: 10.1016/S0140-6736(24)00756-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00756-6/abstract