Maternal and paternal carriage of the annexin A5 M2 haplotype: a possible risk factor for recurrent implantation failure
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GENETICS
Maternal and paternal carriage of the annexin A5 M2 haplotype: a possible risk factor for recurrent implantation failure (RIF) Nina Rogenhofer 1 & Arseni Markoff 2 & Xenia Ennerst 1 & Nadja Bogdanova 2 & Christian Thaler 1 Received: 7 July 2020 / Revised: 30 September 2020 / Accepted: 12 October 2020 # The Author(s) 2020
Abstract 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. Keywords M2 Haplotype . Annexin . Recurrent implantation failure
Introduction Recurrent implantation failure (RIF) is determined when morphologically good quality embryos repeatedly fail to implant after numerous IVF/ICSI treatment attempts [1–5]. There are several variations to the criteria for defining RIF [2]. Some definitions include the numbers of failed ART Nina Rogenhofer and Arseni Markoff contributed equally to this work. * Nina Rogenhofer [email protected] 1
Division of Gynecological Endocrinology and Reproductive Medicine, Department of Gynaecology and Obstetrics, University Hospital of the Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany
2
Institute of Human Genetics, UKM and WWU, Muenster, Germany
cycles and the numbers of transferred embryos. For example, Polanski et al. assess RIF as ≥ 2 consecutive unsuccessful transfers with ≥ 4 embryos or 2 blastocysts of high quality [6]. Others include female age as an additional criterion
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