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Low Molecular Weight Heparin-Aspirin-Prednisolone Combination Does Not Increase the Live Birth Rate in Recurrent Implantation Failure: A Retrospective Cohort Study

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Abstract

This study investigates the triple combination of adjuvants (low molecular weight heparin (LMWH)-aspirin-prednisolone) whether it improves the live birth rates of IVF&ICSI patients with previous implantation failure. This retrospective study included 1095 patients with >2 failed either fresh or frozen single embryo transfer cycles between 2014 Jan and 2021 Jan. Patients were divided into two subgroups. Group A consisted of patients with only vaginal progesterone for luteal phase support. Group B consisted of patients with triple (daily subcutaneous LMWH, daily 150 mg aspirin, and daily 16 mg prednisolone) luteal phase supplementation to vaginal progesterone. Demographic parameters, cycle characteristics, embryology, and pregnancy outcomes were compared, and the study’s primary outcome was the live birth rate. Demographic parameters were similar between the groups. Positive b-hCG, miscarriage, and live birth rates were similar between groups as Group A vs. Group B, positive b-hCG 30.8% (190/617) vs. 35.4% (169/478), miscarriage rates 4.4% (27/617) vs. 6.7% (32/478), and live birth rates 20.4% (126/617) vs. 23.8% (114/478), respectively. When patients were stratified according to previous failures, live birth rates were still similar. Pregnancy outcomes were significantly improved in only patients with diminished ovarian reserve (Group A vs. Group B, positive b-hCG 24.2% vs. 34.3%, live birth rate 12.1% vs. 21.9%, p < 0.01). Whether the embryo transfer was fresh or frozen-thawed did not affect the results. A combined supplementation of LMWH, aspirin, and prednisolone in the luteal phase does not improve live birth rates of IVF&ICSI patients with previous implantation failure except potentially for patients with diminished ovarian reserve.

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Data Availability

All data generated or analyzed during this study are included in this published article and are available from the corresponding author on reasonable request.

Code Availability

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Acknowledgements

We are thankful for tireless efforts of our ART center nurses and staff for their precious contributions in all stages of our investigation.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Obstetrics and Gynecology, Bursa Uludag University, Bursa, Turkey

    Kiper Aslan, Isil Kasapoglu, Ceren Cinar & Gurkan Uncu

  2. Faculty of Medicine, Department of Histology and Embryology, Bursa Uludag University, Bursa, Turkey

    Cihan Cakir & Berrin Avci

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  1. Kiper Aslan
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  2. Isil Kasapoglu
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  3. Ceren Cinar
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Contributions

GU designed the study. CCe participated in data collection. IK performed interpretation. KA organized and wrote the manuscript. CCi and BA reviewed. GU approved the final version.

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Correspondence to Gurkan Uncu.

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Ethics approval for the study was obtained from the Bursa Uludag University Clinical Trials Ethical Committee (2021-17/42).

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Aslan, K., Kasapoglu, I., Cinar, C. et al. Low Molecular Weight Heparin-Aspirin-Prednisolone Combination Does Not Increase the Live Birth Rate in Recurrent Implantation Failure: A Retrospective Cohort Study. Reprod. Sci. 30, 3253–3260 (2023). https://doi.org/10.1007/s43032-023-01233-9

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