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      Efficacy of low‐molecular‐weight heparin on the outcomes of in vitro fertilization/intracytoplasmic sperm injection pregnancy in non‐thrombophilic women: a meta‐analysis

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          Abstract

          Introduction

          The aim of our study was to evaluate the effect of low‐molecular‐weight heparin on pregnancy outcomes in women without thrombophilia during in vitro fertilization/intracytoplasmic sperm injection treatment.

          Material and methods

          We searched Pubmed, Web of Science, Embase, Cochrane and CNKI (from inception to 2 February 2018). Our study identified randomized controlled trials or quasi‐randomized controlled trials comparing low‐molecular‐weight heparin subcutaneous treatment with no treatment or only luteal support control. The outcomes included live birth rate, clinical pregnancy rate and miscarriage rate.

          Results

          Five trials, including 935 women receiving in vitro fertilization/intracytoplasmic sperm injection treatment, were included in meta‐analyses. There were 458 women receiving low‐molecular‐weight heparin and 477 in the control group. No significant differences for live birth rate, clinical pregnancy rate and miscarriage rate were found between the low‐molecular‐weight heparin and control groups. Of them, four trials reported live birth rate as an outcome and the risk ratio was 1.13 (95% confidence interval 0.88–1.43, p = 0.34). All five trials reported clinical pregnancy rate as an outcome, the risk ratio was 1.08 (95% confidence interval 0.87–1.32, p = 0.47). Three trials reported miscarriage rate and the risk ratio was 0.58 (95% confidence interval 0.30–1.10, p = 0.09). In women with two or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratio of live birth rate was 1.15 and the risk ratio of clinical pregnancy rate was 1.17. In women with three or more failed in vitro fertilization/intracytoplasmic sperm injection cycles, the risk ratios of live birth rate and clinical pregnancy rate were 1.36 and 1.35, respectively.

          Conclusions

          Our results suggested that low‐molecular‐weight heparin had no effect on pregnancy success rate in non‐thrombophilic women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. However, to justify the use of low‐molecular‐weight heparin in clinical practice, multicenter trials are still necessary.

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          Most cited references30

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          Cochrane Methods 2016

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            Clinical guidelines for testing for heritable thrombophilia.

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              Aspirin plus heparin or aspirin alone in women with recurrent miscarriage.

              Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                lucia@imm.ac.cn
                Journal
                Acta Obstet Gynecol Scand
                Acta Obstet Gynecol Scand
                10.1111/(ISSN)1600-0412
                AOGS
                Acta Obstetricia et Gynecologica Scandinavica
                John Wiley and Sons Inc. (Hoboken )
                0001-6349
                1600-0412
                05 June 2018
                September 2018
                : 97
                : 9 ( doiID: 10.1111/aogs.2018.97.issue-9 )
                : 1061-1072
                Affiliations
                [ 1 ] Department of Obstetrics and Gynecology Peking University First Hospital Beijing China
                [ 2 ] State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia Medica of Peking Union Medical College Beijing China
                Author notes
                [*] [* ] Correspondence

                Xiu‐Ying Yang, State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica of Peking Union Medical College, Beijing, China.

                E‐mail: lucia@ 123456imm.ac.cn

                Author information
                http://orcid.org/0000-0001-8500-3128
                Article
                AOGS13359
                10.1111/aogs.13359
                6100106
                29700821
                b3e5946c-3693-4251-b805-24be738d03b9
                © 2018 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG)

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 02 February 2018
                : 17 April 2018
                Page count
                Figures: 5, Tables: 2, Pages: 12, Words: 6677
                Funding
                Funded by: CAMS Initiative for Innovative Medicine
                Award ID: CAMS‐I2M2016‐I2M‐3‐007
                Funded by: National Natural Science Foundation of China
                Award ID: 81470159
                Award ID: 81490745
                Funded by: National Major Research Development Program of China
                Award ID: 2016YFC1000905
                Categories
                Systematic Review
                Systematic Reviews
                Custom metadata
                2.0
                aogs13359
                September 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:20.08.2018

                Obstetrics & Gynecology
                low‐molecular‐weight heparin,in vitro fertilization/intracytoplasmic sperm injection,non‐thrombophilia,pregnancy outcomes,randomized controlled trial

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