PROPHYLACTIC DOSE ENOXAPARIN MAY INCREASE PREGNANCY RATES IN MEN WITH ABERRANT SPERM METHYLATION PROFILES

Several studies have reported an association between abnormal sperm methylation profiles and male factor infertility or poor embryo development1,2. While many factors such as smoking, increased BMI, and advanced paternal age are known to influence the sperm methylome, there are currently no known treatment options to overcome the infertility associated with abnormal sperm methylation. To report experience treating the female partner of men who have abnormal methylation in at least one of the HLA genes with prophylactic-dose enoxaparin (low molecular-weight heparin). Men presenting for fertility treatment received an epigenetic sperm profiling test. The female reproductive partner of a subset of men with epigenetic abnormalities in at least one of the HLA genes were treated with prophylactic-dose enoxaparin. Outcomes of cycles with and without treatment are presented here. Abnormal sperm methylation profiles are those which differ from known fertile sperm donors. Of 79 men tested in a 12-month period, 24 men were identified with abnormal methylation in at least one of the HLA genes. Six couples had at least one treatment cycle in which the female partner was treated with enoxaparin; these six couples had a total of 14 treatment cycles. Of the nine cycles in which the female partner received enoxaparin, five (55.6%) resulted in an on-going pregnancy, compared with 0% in the group not receiving enoxaparin. Of patients who had at least one non-enoxaparin cycle followed by at least one treated cycle, none of the untreated cycles resulted in on-going pregnancy, while all of the enoxaparin-treated cycle did. Of note, two couples received enoxaparin for all of their cycles (5 combined); of these, there were two biochemical pregnancies, two 1st trimester miscarriages, and one on-going pregnancy. One of these biochemical losses and two of these 1st trimester losses were from cycles using an egg donor. In this set of patients, prophylactic-dose enoxaparin treatment was associated with higher on-going pregnancy rates. These patients were selected based on the presence of abnormal sperm HLA methylation and data suggesting a possible role of low-dose heparin in immunosuppression3; however, it is possible the increase in pregnancy was due to a mechanism unrelated to the sperm HLA methylation. Though a larger study is needed to determine if a true relationship exists between sperm HLA methylation and success with enoxaparin treatment, this data does suggest a potential next step for couples who have otherwise been unsuccessful with IVF.