2.

Clinical Pregnancy
Use of Aspirin and Low Molecular Weight Heparin (LMWH) in Women with Recurent Spontaneous Abortions (RSA) and Primary Antiphospholipid Syndrome; a Retrospective Study.
Evangelos Ntrivalas, Harilaos Mantouvalos, Nikolaos Tsagaris, Theodoros Hatzis, Joanne Kwak-Kim, Alan Beer Center of Immunological Evaluation of RSA, Athens, Greece; Reproductive Medicine, FUHS/The Chicago Medical School, N. Chicago, IL, USA

Primary antiphospholipid syndrome has been correlated with recurrent spontaneous abortions (RSA). Pregnant women with antiphospholipid antibodies have an increased risk of spontaneous abortion, intrauterine fetal demise, stillbirth and preeclampsia. Treatment with low dose aspirin and low-molecular-weight-heparin (LMWH) has been shown to improve pregnancy outcome in these women. However, the initiation time of anticoagulant treatment varies widely from preconception to a positive fetal heart beat. The purpose of this study is to determine the optimal time of treatment with low dose aspirin and LMWH in women with history of 2 or more RSA and primary antiphospholipid syndrome. Total 399 women who became pregnant at the Center of Immunological Evaluation of RSA were retrospectively analyzed. Nine women, who miscarried with an abnormal karyotype, were excluded. Total 390 RSA patients comprised four study groups. Three treatment groups received low dose aspirin (85mg orally once daily) and LMWH, tinzaparin sodium 3,500 IU (0.3ml) subcutaneously, once daily, started as follows: 1) Group I (n=120), on the first day of the menstrual cycle of the cycle of conception; 2) Group II (n=144), 48h after ovulation; 3) Group III (n=78), 35-40 days after the onset of menses. Group IV (n=48), received no treatment. Women in all groups had one or more positive antiphospholipid antibodies. Successful pregnancy outcome was defined as a delivery of a live born infant, either vaginal or by cesarean section. There were 187 deliveries and 203 miscarriages in all four groups. Overall success rate of LMWH and low- 8 dose aspirin in treatment groups (regardless of the initiation differences) was 54% versus 6.3% in the no treatment group (p<0.000). In group I, 107 (89.2%) women delivered a live born infant, whereas 13 (10.8%) miscarried. In group II, 68 (47.2%) women delivered and 76 (52,8%) miscarried. In group III, 9 (11.5%) women delivered and 69 (88.5%) miscarried and in group IV 3 (6.3%) women delivered and 45 (93.7%) miscarried. There was a statistically significant difference in the success rate in the four groups, (p<0.000). This study showed that LMWH and low-dose aspirin treatment significantly increases successful pregnancy rates. Women who initiated treatment on the first day of the cycle of conception demonstrated the highest success rate than other groups who started treatment later in the cycle of conception.

In conclusion, treatment with low-dose aspirin and LMWH in women with RSA and primary antiphospholipid syndrome significantly improves pregnancy outcome when it is started on the first day of the menstrual cycle of the cycle of conception. A further study is warranted to investigate the effect of LMWH and low-dose aspirin in angiogenesis of endometrium as well as placental vascular development. Dr. Harilaos Mantouvalos Obstetrician Gynecologist Professor Athens University Professor of Microbiology-Immunology, Obstetrics and Gynecology - Chicago Medical School Ypsilantou 43 Kolonaki Athens - Greece +30 210 722 8845 http://www.infertility.gr