Objective

This study was carried out to determine the potential role of the M2/ANXA5 haplotype as a risk factor for recurrent implantation failure (RIF). Carriage of the M2/ANXA5 haplotype that induces prothrombotic changes has been implicated in failure of early pregnancies and placenta-mediated complications (preeclampsia, IUGR, preterm birth).

Material and methods

In the present case control study, 63 couples (females and males) with RIF presenting for IVF/ICSI to the Fertility Center of [masked] were analyzed. RIF was defined as ≥ 4 consecutive failed ART-transfers of ≥ 4 blastocysts or ≥ 8 cleavage-stage embryos of optimal quality and maternal age ≤ 41. Fertile female controls (n = 90) were recruited from the same center. Population controls (n = 533) were drafted from the PopGen biobank, UKSH Kiel.

Results

Couples carrying the M2/ANXA5 haplotype turned out to have a significantly increased relative risk (RR) for RIF. Compared with female fertile controls, RR was 1.81 with p = 0.037 (OR 2.1, 95%CI 1.0–4.3) and RR was 1.70, with p = 0.004 (OR 2.0, 95%CI 1.2–3.1) compared with population controls (15.4% M2 carriers). Male partners were comparable with RIF females for M2/ANXA5 haplotypes (28.6% vs. 23.8%, p = 0.54). RIF females compared with population controls had a RR of 1.55 (p = 0.09) and RIF males compared with population controls had a RR of 1.9 (p = 0.01). Couples with ≥ 7 failed transfers showed a RR of 1.82 (p = 0.02) compared with population controls.

Conclusion

Our findings suggest that maternal as well as paternal M2/ANXA5 haplotype carriages are risk factors for RIF. These results allow new insights into the pathogenesis of RIF and might help to identify relevant risk groups.

中文翻译：

---

膜联蛋白A5 M2单倍型的母体和父体携带：复发性植入失败（RIF）的可能危险因素

目的

进行这项研究以确定M2 / ANXA5单倍型作为复发性植入失败（RIF）的危险因素的潜在作用。M2 / ANXA5单体型的运输会引起血栓形成的改变，这与早孕失败和胎盘介导的并发症（先兆子痫，IUGR，早产）有关。

材料与方法

在本病例对照研究中，分析了63具RIF夫妇（男女）到IVF / ICSI到[假装]生育中心。RIF被定义为≥4个囊胚或≥8个卵裂期胚胎的连续4次ART转移失败，其质量最佳且母体年龄≤41。从同一中心招募可育女性对照（n = 90）。人口控制（n = 533）是由UKSH Kiel的PopGen生物库起草的。

结果

事实证明，携带M2 / ANXA5单倍型的夫妇的RIF相对风险（RR）显着增加。与女性可育对照相比，与人群对照相比，RR为1.81，p = 0.037（OR 2.1，95％CI 1.0-4.3），RR为1.70，p = 0.004（OR 2.0，95％CI 1.2-3.1） ％M2运营商）。对于M2 / ANXA5单倍型，男性伴侣与RIF雌性相当（28.6％对23.8％，p = 0.54）。与人口对照组相比，RIF雌性的RR为1.55（p = 0.09），与人口对照组相比，RIF雄性的RR为1.9（p = 0.01）。与人口对照组相比，转移≥7次的夫妇的RR为1.82（p = 0.02）。

结论

我们的研究结果表明，母体和母体M2 / ANXA5单倍型支架是RIF的危险因素。这些结果为RIF的发病机理提供了新的见解，并可能有助于确定相关的风险组。