Influence of maternal thrombophilia status on the outcome of assisted reproduction

The chances of pregnancy after a first attempt of assisted reproduction technologies (ART) are about 30%. Pregnancy rate progressing to term and resulting in live birth of a child is somewhat lower, 25%. Repeated cycles of ART increase success rate. However, a substantial number of couples fail to achieve pregnancy after three cycles. Thrombophilia has been suggested to play a role in failure of ART by interfering with embryo implantation and placentation but available evidence remains controversial. Large prospective studies to confirm this hypothesis are lacking. The objective of our study is to investigate the association of thrombophilia with outcome of ART in women with recurrent, unexplained failure of assisted reproduction. We set up a prospective study including women with a history of at least three failures of fresh ART cycles with replacement of one or two good quality embryos. Blood samples are taken before the start of a next treatment cycle to avoid influence of ovarian stimulation on coagulation parameters. All women are tested for inherited thrombophilia (antithrombin activity, protein C activity, free protein S antigen, factor V Leiden and prothrombin G20210A mutation) and evaluated for the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin and anti-(beta)2GPIb antibodies). Study end point is reached after live birth or failure of ART after six treatment cycles. Follow-up information is obtained from the patients' medical records. Implantation rate, clinical pregnancy rate and live birth rate are defined according to the ICMART glossary of ART terminology. Stimulation cycles where aspirin, low molecular weight heparin and/or corticosteroids were used, were excluded as these drugs could influence outcome. This study was approved by the medical ethics committee of the University Hospital of Brussels. All patients signed informed consent. Between 2008 and 2012, 136 women were enrolled. Today, sixty-one women have reached study end point. Twenty-one women had a liveborn baby while 40 did not. There were no significant differences in prevalence of thrombophilia between the two groups. Positivity for antiphospholipid antibodies was the most prevalent parameter among the two study groups, 5% (1/21) in the live birth group and 22% (9/ 40) in the non-live birth group (P = 0.13). After inclusion, these 61 women underwent a total of 111 ART cycles. Cycles with interfering drug use were excluded, leaving 77 cycles for investigation. Implantation rate and clinical pregnancy rate were not statistically different in women with inherited and/or acquired thrombophilia compared to women without thrombophilia. There is, however, a trend towards lower live birth rate in the patient group with thrombophilia compared to the group without, 4.8% (1/21) and 18.5% (10/54) respectively (P = 0.13). These results suggest that there is no significant association between maternal thrombophilia and failed embryo implantation. A slight trend towards lower live birth rate in women with thrombophilia was observed. The results presented here are the preliminary data of a large, prospective study that is still ongoing and thus need to be considered with caution. Failure to demonstrate statistical significance may be due to the limited sample size of this interim analysis.