Department of Infertility, Institute of Reproductive Medicine, Salt Lake City, Kolkata, West Bengal, India.
PLoS One. 2013 Sep 5;8(9):e74155. doi: 10.1371/journal.pone.0074155. eCollection 2013.
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.
复发性流产(RPL)的管理仍然是一个巨大的挑战,多囊卵巢综合征(PCOS)患者自然流产的风险更高。低分子肝素(LMWH)治疗已成为 RPL 患者的一种公认的治疗选择;然而,尚未精确确定可能对 LMWH 有反应的女性亚组。本研究评估了 LMWH 对 PCOS 及相关代谢表型(包括高同型半胱氨酸血症(HHcy)、胰岛素抵抗(IR)和肥胖)的疗效。这项前瞻性观察性研究在印度加尔各答生殖医学研究所进行。共筛选了 967 名有 2 次或以上连续早期流产史的妇女,其中 336 名被选为研究对象。入选患者最初根据是否存在 PCOS 进行分组,随后根据 HHcy、IR 和/或肥胖进行分层。在第一个治疗周期不成功的情况下,患者在一个受孕周期中接受阿司匹林治疗,在下一个受孕周期中接受阿司匹林-LMWH 联合抗凝治疗。妊娠挽救是唯一的结局指标。阿司匹林治疗后的妊娠挽救总成功率为 43.15%,这主要代表了同型半胱氨酸正常的女性,而 HHcy 人群的挽救率较低,无论是否存在 PCOS、IR 或肥胖。相比之下,阿司匹林-LMWH 联合治疗可挽救阿司匹林治疗失败病例中的 66.84%的妊娠。逻辑回归分析显示,在控制其他混杂因素后,HHcy 仍然是预测 PCOS、IR 和肥胖亚组挽救率的重要因素。就妊娠挽救而言,阿司匹林和 LMWH 的联合抗凝治疗为 HHcy 表型患者带来了额外的益处。