Pregnancy Outcome in Patients With a History of Recurrent Spontaneous Miscarriages and Documented Thrombophilias

Abstract

Thrombophilic disorders and hyperhomocystinemia (HHC) with or without the presence of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms have recently been identified as potential causes of recurrent spontaneous miscarriage (RSM), although some studies failed to confirm this association. Only limited data have been published on pregnancy outcome in women with a history of RSM and documented thrombophilia while receiving active treatment. This study was conducted on 85 women referred to the Recurrent Prepregnancy Loss Clinic of the Reproductive Medicine Unit, Repromed, South Australia, between November 1999 and November 2001 because of a history of recurrent miscarriages. Recurrent pregnancy loss was defined as 2 or more spontaneous embryonic and/or fetal losses. After exclusion of women with a known cause of recurrent spontaneous abortion, data for 76 subjects were analyzed. Subjects were tested in the nonpregnant state for protein S deficiency, activated protein C resistance, factor V Leiden genotype, prothrombin gene mutation, lupus anticoagulant, HHC, MTHFR, antinuclear antibodies, and thyroid antibodies. All women with unequivocal thrombophilic disorders and a subsequent pregnancy were treated with a combination of low-dose aspirin (LDA) plus low molecular weight heparin (LMWH). Forty-nine (64.5%) of 76 women with RSM were found to be positive for 1 or more thrombophilias. In addition, 6 (10.5%) of 57 women tested for HHC were positive. Thirty (60.5%) of 50 women tested for MTHFR mutations were found to be either heterozygous or homozygous for 1 of the mutations. In the group of women with HHC and/or 1 of the MTHFR mutations, 22 became pregnant, of which 17 pregnancies (77.3%) resulted in a live birth. Five pregnancies (22.7%) resulted in a pregnancy loss, 1 of which was a Turner syndrome and 1 a trisomy-16. There were 3 unexplained losses (13.6%). Twenty-seven women with 1 or more thrombophilia disorders conceived after treatment with LDA plus LMWH. Twenty (74.1%) resulted in a live birth and 7 resulted in pregnancy loss, 1 of which was an ectopic pregnancy and 1 was a trisomy-21. The unexplained pregnancy loss rate was 14.8%. None of the pregnancies treated with LDA and LMWH were complicated by serious blood loss or placental abruption. Ten women delivered prematurely (including 3 twin pregnancies), 2 developed preeclampsia, and 1 had intrauterine growth restriction.