OBJECTIVE

目的

Recurrent implantation failure (RIF) is a term coined to denote multiple failures after embryo transfer. While this term is commonly used, the diagnostic criteria for RIF and its true prevalence have not been established. A recent study demonstrated that less than 5% of patients with normal uterine anatomy fail to conceive after 3 consecutive single euploid embryo transfers, and that implantation and live birth rates are similar after the first, second and third attempt (Pirtea, Fertil Steril 115:45-52, 2021). The objective of our study was to evaluate the clinical pregnancy rate (CPR) and live birth rate (LBR) beyond three euploid transfers in an effort to determine whether there is a number of euploid embryo transfer attempts after which a significant decline in implantation rate (indicative of an underlying endometrial pathology) is observed.

反复种植失败（RIF）是一个术语，用来表示胚胎移植的多次失败。虽然这个术语很常用，但反复种植失败的诊断标准及其真实的患病率标准尚不明确。最近的一项研究表明，在具有正常子宫解剖结构的患者中，其在连续3次单个整倍体胚胎移植后仍不能怀孕的发生率低于5%，其着床率和活产率在第一次、第二次和第三次胚胎移植后结果是相似的（Pirtea，Fertil Steril 115：45-52，2021）。我们的研究目的是评估超过三次正常染色体胚胎移植后的临床妊娠率（CPR）和活产率（LBR），以确定是否存在一定数量的正常染色体胚胎移植尝试后，着床率显著下降（表明存在潜在的子宫内膜病理）。

MATERIALS AND METHODS

材料和方法

This was an international multi-center retrospective cohort study among patients who failed three or more consecutive frozen euploid embryo transfers between 2012 to 2022. Fertility groups in four different countries (a total of 26 individual clinics) were included. Cycles using donor eggs, gestational carriers, PGT-M, and patients with uterine anomalies, hydrosalpinx, adenomyosis, non-obstructive azoospermia, and endometrial thickness <6mm prior to transfer were excluded. Chi-square was used for comparison of categorical variables. T-test was used for comparison of continuous variables. Relative risks with 95% confidence intervals were calculated to compare outcomes between the fourth and fifth embryo transfer. P value <0.05 was considered significant.

这是一项国际多中心回顾性队列研究，研究对象为2012年至2022年期间连续3次或3次以上冷冻整倍体胚胎移植失败的患者。包括四个不同国家的生育组（共有26个独立研究所）。排除了使用供卵、代孕、PGT-M以及子宫异常、输卵管积水、子宫腺肌症、非阻塞性无精子症和移植前子宫内膜厚度<6mm的患者。采用卡方检验比较分类变量，采用t检验比较连续变量。计算相对风险和95%置信区间，以比较第四次和第五次胚胎移植的结果。P<0.05表示差异有统计学意义。

RESULTS

结果

During the study period, 123,987 patients underwent an egg retrieval and 94,401 had an embryo transfer, with a total of 64,572 euploid embryo transfers performed in participating centers. At baseline, mean age was 34.6 ± 3.8, median AMH was 2.74 (1.04-4.13) ng/mL and mean BMI was 24.7 ± 4.7 kg/m2. There were no clinically significant differences in baseline patient characteristics when comparing the different clinics included for analysis. A total of 105 patients underwent a fourth consecutive euploid transfer, and 45 patients underwent a fifth consecutive euploid transfer. The mean endometrial thickness prior to transfer was 8.6 ± 1.5mm. The CPR after the fourth and fifth euploid embryo transfer was 51.4% and 62.2%, respectively. The LBR after the fourth and fifth euploid embryo transfer was 40% and 53.3%, respectively. When comparing the fourth and fifth transfer, there was no significant difference in CPR (RR = 1.21 (0.9-1.6), p = 0.23) or LBR (RR = 1.33 (0.93-1.9), p = 0.14).

在研究期间，对123,987例患者进行了取卵，94,401例患者进行了胚胎移植，在参与中心共进行了64,572例整倍体胚胎移植。她们的基线特征，平均年龄为34.6±3.8岁，中位AMH为2.74（1.04-4.13）ng/mL，平均BMI为24.7±4.7kg/m2。比较纳入分析的不同研究所，患者的基线特征没有显著差异。共有105例患者进行了连续第4次整倍体移植，45例患者进行了连续第5次整倍体移植。移植前子宫内膜平均厚度为8.6±1.5 mm。第4次和第5次整倍体胚胎移植后的临床妊娠率分别为51.4%和62.2%。第4次和第5次整倍体胚胎移植后的活产率分别为40%和53.3%。在比较第4次和第5次移植时，CPR（RR=1.21（0.9-1.6），p=0.23）和LBR（RR=1.33（0.93-1.9），p=0.14）的差异均无统计学意义。

CONCLUSIONS

结论

Our study is the first and largest completed to date that evaluates the CPR and LBR after a fourth or fifth consecutive frozen euploid embryo transfer. The CPR and LBR did not significantly decrease by the fifth consecutive euploid embryo transfer, suggesting that true RIF might be even rarer than previously assumed.

我们的研究是迄今为止第一个完成的也是最大的一个评估第4或第5次连续冷冻整倍体胚胎移植后的临床妊娠率和活产率的研究。在连续第5次整倍体胚胎移植时，临床妊娠率和活产率并没有显著降低，这表明真正的反复种植失败患病率可能比之前的假设更罕见。

IMPACT STATEMENT

影响陈述

Recurrent implantation failure is an incredibly rare occurrence (<1%) after five consecutive euploid embryo transfers in patients with otherwise good prognosis.

在排除其他影响因素的患者中，连续5次整倍体胚胎移植后，反复种植失败的发生率非常罕见，不到1%。

文章来源：

DOES RECURRENT IMPLANTATION FAILURE EXIST? PREVALENCE AND OUTCOMES OF FIVE CONSECUTIVE EUPLOID BLASTOCYST TRANSFERS IN 123,987 PATIENTS Gill, Pavan et al.Fertility and Sterility, Volume 120, Issue 4, e177 - e178