Human Reproduction, Vol. 14, No. 6, 1624-1627,
June 1999
© 1999 European Society of Human Reproduction and Embryology
A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure
1 Department of Obstetrics and Gynecology and 2 Haematology unit, Bnai-Zion Medical Center, Rappaport Faculty of Medicine, Technion, 47 Golomb St, PO Box 4049, Haifa 31048, Israel
Thrombophilia was recently suggested as a possible factor in recurrent pregnancy losses. We studied prospectively 125 patients (mean age 31.4 ± 5.6 years) with one or more first or second trimester pregnancy losses for the prevalence of activated protein C resistance (APCR). Proteins C and S antigens, antithrombin III, anticardiolipin, and lupus anti-coagulant were also evaluated. Patients with uterine malformations, hormonal abnormalities, chromosomal translocations and infectious causes were excluded. A control group of 125 women with no past fetal loss were matched with the study group. Whenever the APC–sensitivity ratio (APC–SR) was 
2.2, polymerase chain reaction for factor V mutation (Leiden) was performed. Heterozygosity for the mutation was found in 18 patients (14.4%) compared with seven heterozygous among 125 control group (5.6%; P < 0.05). Acquired APCR (APC–SR 1.8 and Leiden negative) was revealed in seven patients (5.6%) in the study group and in three of the controls (2.4%; not significant). The rate of preclinical pregnancy losses (17/48) and second trimester miscarriages (10/48) in mutation carriers was significantly higher than in patients with no APCR (25/214) and (14/214) respectively (P < 0.001and P < 0.01 respectively). Live birth rate was not different between the two groups. Occurrence of APCR with any kind of pregnancy loss calculated per patient, in our study group, was ~1/7, 1/4 and 1/5 with one, two and three or more pregnancy losses respectively. These findings suggest that assessment of APCR should be considered in a more extended evaluation of such patients.
Key words: activated protein C resistance/factor V mutation/repeated miscarriages/thrombophilia
3 To whom correspondence should be addressed
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