DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20194839

A prospective randomized controlled trial showing efficacy of luteal phase low molecular weight heparin in fresh non-donor IVF/ICSI cycles in women with previous implantation failures

Neeta Singh, Rohitha Cheluvaraju, Sunesh Kumar Jain

Abstract


Background: Implantation failure is a major challenge in in-vitro fertilization (IVF) cycles. The present study was undertaken to determine the immunomodulatory effects of heparin in patients with previous implantation failures undergoing assisted reproductive techniques (ART).

Methods: This was a prospective randomized controlled trial with sample size of 100 patients who had history of at least one previously failed IVF/ICSI. Study group of 50 patients received heparin and 50 patients in control group received routine luteal phase support.

Results: Primary outcome of the study was implantation rate (IR) which was 11.03% in the study group was and 5.48% in the control group (p=0.08). Biochemical pregnancy rate and clinical pregnancy rate in the study group was 18% and 12% in the control group (p=0.401). Calculated live birth was 5.15% and 3.42% in the study and control groups respectively (p=0.562). 11 babies were taken home from the study group and 6 from the control group (p=0.18).

Conclusions: The result of this pilot study showed relative increase in implantation rates (IR) suggesting beneficial effects of heparin in patients with repeated implantation failures. Although these changes are not statistically significant, the presence of an increasing trend in all the outcome parameters signify the possible benefits of heparin proving for the present study hypothesis.


Keywords


Adjuvant therapy, Heparin, Implantation rate, Immunomodulator, Implantation failure, Luteal phase support, Recurrent

Full Text:

PDF

References


Turnbull LW, Lesny P, Killick SR. Assessment of uterine receptivity prior to embryo transfer: a review of currently available imaging modalities. Hum Reprod Update. 1995;1(5):505-14.

Tazuke SI, Giudice LC. Growth factors and cytokines in endometrium, embryonic development, and maternal: embryonic interactions. Semin Reprod Endocrinol. 1996;14(3):231-45.

Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil Steril. 2005;83(3):684-90.

Urman B, Ata B, Yakin K, Alatas C, Aksoy S, Mercan R, et al. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial. Hum Reprod. 2009;24(7):1640-7.

Hamdi K, Danaii S, Farzadi L, Abdollahi S, Chalabizadeh A, Sabet AS. The role of heparin in embryo implantation in women with recurrent implantation failure in the cycles of assisted reproductive techniques (without history of thrombophilia). J Fam Reprod Health. 2015;9(2):59-64.

Nelson SM, Greer IA. The potential role of heparin in assisted conception. Hum Reprod Update. 2008;14(6):623-45.

Wilcox A, Baird D, Weinberg C. Time of Implantation of the conceptus and loss of pregnancy. New Eng J Med. 1999;340(23):1796-9.

DiSimone N, Caliandro D, Castellani R, Ferrazzani S, DeCarolis S, Caruso A. Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with anti-phospholipid syndrome. Hum Reprod. 1999;14(2):489-95.

Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody induced fetal loss by inhibiting complement activation. Nat Med. 2004;10(11):1222.

Altmäe S, Koel M, Võsa U, Adler P, Suhorutšenko M, Podar LT, et al. Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers. Sci Rep. 2017;15:66-9.

Potdar N, Gelbaya TA, Konje JC, Nardo LG. Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(6):674-84.