Activated protein C resistance and factor V Leiden mutation can be associated with first- as well as second-trimester recurrent pregnancy loss

PROBLEM: To examine whether the occurrence of activated protein C resistanc e (APCR) and factor V Leiden mutation differs in women with first- compared to women with second-trimester unexplained recurrent pregnancy loss. MEHTOD OF STUDY: Seventy eight consecutive women with two or more unexplain ed post-embryonic recurrent pregnancy losses and 139 fertile women with at least one successful pregnancy and no abortions were prospectively investig ated for APCR and the factor V Leiden mutation. No women were pregnant at t he time of investigation. APCR was defined as APC-sensitivity ratio (APC-SR ) of less than or equal to 2.0. All patients with an APC-SR less than or eq ual to 2.4 were investigated for the factor V Leiden mutation. Women in thi s study were divided into three groups. Group A included only women with a history of recurrent first-trimester embryonic loss (37 women) and Group B included women with second-trimester abortions with or without additional f irst-trimester abortions (41 women). Group C included the controls (139 wom en). RESULTS: APCR and factor V Leiden mutations were significantly more prevale nt in all recurrent pregnancy loss patients in this study as compared to co ntrols, 38% (30/78) and 19% (15/78) in contrast to 8% (11/139) and 6% (8/13 9), respectively. All three groups in the study were comparable regarding a ge, parity, and number of living children, whereas Groups A and B were also comparable regarding gravidity. Mean APC-SRs were significantly higher in Group C as compared to Groups A and B. The incidence of APCR was significan tly higher in Groups A and B, as compared to controls, 27 and 49% in contra st to 8%. respectively. Moreover, the incidence of the factor V Leiden muta tion was significantly higher in Groups A and B as compared to Group C, 16 and 22% as distinct from 6%, respectively. The incidence of APCR was higher in Group B as compared to Group A, 49% in contrast to 27%, with borderline significance; however, the factor V Leiden mutation did not significantly differ between the two groups. CONCLUSIONS: APCR and factor V Leiden are associated with unexplained recur rent pregnancy loss. The occurrence of APCR and factor V Leiden seems to be linked to post-embryonic first-trimester as well as second-trimester recur rent pregnancy loss. The significance of acquired, non-heritable APCR in re current fetal loss patients, especially in the second-trimester aborters, i s still to be determined.