OBJECTIVE

目的

Emerging data suggests the optimal means to prepare the endometrium for frozen embryo transfer (FET) in women with regular menstrual cycles is an ovulatory, natural cycle. Nevertheless, the lack of timing predictability for a natural cycle FET results in increased scheduling burden on clinic staff as well as requirement for patient flexibility. The aim of this study was to evaluate FET outcomes for women with regular menstrual cycles after natural endometrial preparation, in an effort to support clinical utilization.

新数据表明，对于月经周期规律的女性来说，有排卵的自然周期是冷冻胚胎移植 (FET) 子宫内膜准备的最佳方法。然而，自然周期 FET 缺乏时间可预测性，从而增加了医疗工作人员的排班负担同时也需要患者的灵活性。本研究的目的是评估在月经周期规律的女性中自然周期内膜准备后FET的结果，以支持临床应用。

MATERIALS AND METHODS

材料和方法

This single center, retrospective, maternal age-matched clinical study was a two-part investigation: Part A) first FET outcomes in women with regular menstrual cycles either undergoing modified natural (n=276; mean 35.6 years) or medicated endometrial preparation (n=1,217; mean 35.6 years); Part B) modified natural FET outcomes in women with history of a prior medicated FET cycle (n=134; mean 35.2 years). Modified natural endometrial preparation included hCG trigger, low dose estradiol patches and vaginal progesterone. Implantation with fetal heart tone (FHT), live birth and miscarriage rates following single euploid blastocyst transfer were considered as the primary outcomes. Data was analyzed using a one-way ANOVA, unpaired T-tests with Welch’s correction, Fisher’s exact and Chi-square as appropriate, with significance at p < 0.05.

这研究为单中心、回顾性、与女性年龄匹配的临床研究，分为两个部分进行：A部分是对于经常月经周期的女性进行改良自然周期（n=276；平均年龄35.6岁）或药物治疗的子宫内膜准备（n=1217；平均年龄35.6岁）的首次冷冻胚胎移植（FET）结果的调查；B部分是对于有先前药物治疗FET周期史的女性进行改良自然周期FET结果的研究（n=134；平均年龄35.2岁）。改良自然周期子宫内膜准备包括hCG触发、低剂量雌二醇贴片和阴道孕酮。将单个整倍体囊胚移植后的着床率（有胎心）、活产和流产率作为主要结果进行分析。数据分析采用单因素方差分析、未配对T检验（韦尔奇校正）、fish精确检验和卡方检验，显著性水平为p < 0.05。

RESULTS

结果

For first FET outcomes (Part A), implantation FHT (84.1% vs 70.3%; p < 0.0001; OR 2.23) and live birth rate (79.7% vs 64.0%; p < 0.0001; OR 2.21) after modified natural endometrial preparation were significantly higher than transfers performed in medicated cycles. This was despite the fact that transferred euploid blastocyst quality was significantly better in the medicated FET group (single D5 euploid blastocyst transferred in 66.1% of medicated FETs vs 56.5% in modified natural FETs; p < 0.001). Additionally, lower miscarriage rates trended with women following a modified natural FET cycle (3.9% vs 7.3%; p = 0.07). There were no other significant differences in women’s baseline or IVF cycle characteristics, including endometrial thickness at day of progesterone start, between the two FET groups. For women who had a prior medicated cycle and returned for a second FET with modified natural endometrial preparation (Part B), clinical outcomes were also slightly improved compared to medicated FET cycles; implantation (75.7% vs 70.3%; ns), miscarriage (6.9% vs 7.3%; ns) and live birth rate (70.9% vs 64.0%; ns).

对于之前进行过药物周期并返回进行改良自然子宫内膜准备的女性（部分B），与药物冷冻胚胎移植周期相比，临床结果也稍有改善；种植率（75.7% vs 70.3%; ns）、流产率（6.9% vs 7.3%; ns）和活产率（70.9% vs 64.0%; ns）。对于首次 FET 结果（A 部分），改良自然周期子宫内膜制备后的种植率（84.1% vs 70.3%；p < 0.0001；OR 2.23）和活产率（79.7% vs 64.0%；p < 0.0001；OR 2.21）显著高于人工药物周期。尽管后者移植的单个D5整倍体囊胚质量更好（药物冷冻胚胎移植中66.1%的囊胚为染色体正常囊胚，而改良自然冷冻胚胎移植中为56.5%；p < 0.001），但这并不影响结果。此外，改良自然周期FET的流产率较低（3.9% vs 7.3%; p =0.07）。两组冷冻胚胎移植的女性基线和IVF周期特征，包括孕酮转化日子宫内膜厚度，在两组之间没有其他显著差异。对于之前接受过药物周期并使用改良的天然子宫内膜制剂（B 部分）进行第二次 FET 的女性，与药物 FET 周期相比，临床结果也略有改善；种植率（75.7% vs 70.3%；ns）、流产率（6.9% vs 7.3%；ns）和活产率（70.9% vs 64.0%；ns）。

CONCLUSIONS

结论

In this study, the clinical efficacy of a modified natural endometrial preparation for women with regular cycles, in either a first or second FET, were evaluated to be superior. Despite the difficulty with scheduling natural cycle FETs, the improved clinical benefit and increase in live birth rates would appear to outweigh the lack of timing predictability.

在这项研究中，我们评估了一种改良的自然周期子宫内膜准备方法，用于经期规律的女性进行首次或第二次冷冻胚胎移植，并发现其具有显著的临床疗效。结果显示，这种方法优于其他方法。尽管自然周期冷冻胚胎移植的安排可能会带来一些困难，但改善的临床效果和增加的活产率的优点超过了时间预测的不确定性的缺点。

IMPACT STATEMENT

影响声明

For women with regular cycles, modified natural endometrial preparation represents the preferred method to maximize FET outcomes.

对于经期规律的女性来说，改良的自然周期内膜制备是最优选择，可以最大化冷冻胚胎移植的结果。

参考文献：

MODIFIED NATURAL ENDOMETRIAL PREPARATION MAXIMIZES FET OUTCOMES Patrick, Tonie Michelle et al.Fertility and Sterility, Volume 120, Issue 4, e170