Maternal and paternal carriage of the annexin A5 M2 haplotype: a possible risk factor for recurrent implantation failure (RIF)

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.

Automated summary

Carriage of the M2/ANXA5 haplotype is associated with a significantly increased risk of recurrent implantation failure (RIF) for both maternal and paternal carriers, providing new insights into the pathogenesis of RIF and identifying relevant risk groups.