Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype

Assessment of oocyte quality in polycystic ovarian syndrome and endometriosis by spindle imaging and reactive oxygen species levels in follicular fluid and its relationship with IVF-ET outcome

Objectives: The aim of this study is to examine meiotic spindle in oocytes along with reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to correlate these findings with embryo quality and pregnancy outcome. Materials and Methods: 167 women aged 25-35 years with endometriosis (Group A), polycystic ovarian syndrome (PCOS) (Group B) and tubal block (Group C) were included. Long protocol downregulation using recombinant follicular stimulating hormone was used for ovarian stimulation. Aspirated follicular fluid containing mature oocytes were analyzed for ROS levels and the oocytes were assessed for the presence of meiotic spindle using Cri-OosightTM Polscope. Fertilization, embryo quality, endometrial assessment, and final pregnancy outcome were assessed. Results: Meiotic spindles were visualized in a higher proportion of mature oocytes retrieved from women with endometriosis (66%) as compared to those with PCOS (50.5%) and tubal block (62.3%). ROS levels were also observed to be significantly less in the follicular fluid of oocytes in women with endometriosis (Group A) as compared to the other two groups (P ≤ 0.001). However, pregnancy rates were observed to be lower in Group A (32%) than Groups B (39%) and C (44%), respectively. Within each group, oocytes with spindle visualization yielded a higher number of Grade 1 embryos (P < 0.05) as well as lower ROS levels in follicular fluid (P ≤ 0.001) as compared to those where spindle could not be visualized. Conclusions: There was good correlation between spindle imaging and ROS levels as reliable predictors of oocyte assessment. Women with endometriosis had low ROS levels and good spindle imaging results suggesting a possible role of endometrial receptivity accounting for lower pregnancy rates in these women. Poor oocyte quality, as reflected by higher mean ROS levels and low number of oocytes with spindle visualization, could be the factor impeding pregnancy in women with PCOS as compared to women with tubal block

Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype

Clinical and biochemical characteristics and pregnancy outcomes in the aspirin, and aspirin+LMWH-treated populations.

<p>Values are expressed as mean ± S.D.</p><p>HHcy: hyperhomocysteinemia (Hcy>12 µmol/l); IR: insulin resistance (HOMA2-IR>2.1); NIR: non-insulin resistance; HOMA-2-IR: homeostatic model assessment 2-insulin resistance; obesity: BMI ≥30 kg/m²; pregnancy salvage: uneventful continuation of pregnancy at least until 36^th week.</p>a, b, c<p>Values with different superscripts in a row under specific treatment population differ significantly.</p><p>a <i>vs.</i> b: P<0.037; b <i>vs.</i> c: P<0.002; a <i>vs.</i> c: P<0.016.</p

Raw (%) and adjusted (OR) rates of pregnancy salvage following aspirin treatment.

<p>HHcy: hyperhomocysteinemia (Hcy>12 µmol/l); IR: insulin resistance (HOMA2-IR>2.1); obesity: BMI ≥30 kg/m²; OR: odds ratio; CI: confidence interval.</p><p>Column percentages presented for univariate analysis.</p

Flow chart for patient selection, phenotype distribution, treatment and pregnancy outcome.

<p>Flow chart for patient selection, phenotype distribution, treatment and pregnancy outcome.</p

Raw (%) and adjusted (OR) rates of pregnancy salvage following combined anti-coagulant therapy with aspirin and LMWH treatment.

<p>HHcy: hyperhomocysteinemia (Hcy>12 µmol/l); IR: insulin resistance (HOMA2-IR>2.1); obesity: BMI ≥30 kg/m²; OR: odds ratio; CI: confidence interval.</p><p>Column percentages presented for univariate analysis.</p