Influence of hereditary and acquired thrombophilia on the outcomes of assisted reproductive technology programs

Kraevaya E.E., Dolgushina N.V.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russian
By analyzing the data available in the literature, the authors estimated the influence of hereditary and acquired thrombophilia on the effectiveness of assisted reproductive technology (ART) programs and the efficacy of low-molecular-weight heparins (LMWH) to improve the outcomes of ART programs. The review included data from foreign and Russian articles published over the past 10 years, which were found in the databases of Pubmed, Elsevier, and Cochrane Library on this topic. The role of hereditary and acquired thrombophilia in the effectiveness of ART programs and the use of LMWH to improve the outcomes of ART programs are a debatable issue and require further investigations.

Keywords

assisted reproductive technologies
hereditary thrombophilia
antiphospholipid syndrome
antiphospholipid antibodies
low-molecular-weight heparins

References

  1. Корсак В.С., Смирнова А.А., Шурыгина О.В. Регистр центров ВРТ в России. Отчет за 2015 г. Проблемы репродукции. 2017; 23(5): 8-22. [Korsak V.S., Smirnova A.A., Shurygin O.V. Register of centers of ART in Russia. Report for 2015 Reproduction problems. 2017; 23 (5): 8-22. (InRuss.)]
  2. Bashiri A., Harlev A., Agarwal A., eds. Recurrent pregnancy loss : evidence-based evaluation, diagnosis and treatment. Springer; 2016. 208 p.
  3. Cinnioglu C., Kayali R., Darvin T., Akinwole A., Jakubowska M., Harton G. Aneuploidy screening using next generation sequencing. Methods Mol. Biol. 2019; 1885: 85-102. https://doi.org/10.1007/978-1-4939-8889-1_6.
  4. Alteri A., Corti L., Sanchez A.M., Rabellotti E., Papaleo E., Viganò P. Assessment of pre-implantation genetic testing for embryo aneuploidies: A SWOT analysis. Clin. Genet. 2019; 95(4): 479-87. https://doi.org/10.1111/cge.13510.
  5. Kovalevsky G., Gracia C.R., Berlin J.A., Sammel M.D., Barnhart K.T. Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch. Intern. Med. 2004; 164(5): 558-63. https://doi.org/10.1001/archinte.164.5.558.
  6. Kupferminc M.J., Eldor A., Steinman N., Many A., Bar-Am A., Jaffa A. et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N. Engl. J. Med. 1999; 340(1): 9-13. https://doi.org/10.1056/NEJM199901073400102.
  7. Rodger M.A., Betancourt M.T., Clark P., Lindqvist P.G., Dizon-Townson D., Said J. et al. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med. 2010; 7(6): e1000292. https://doi.org/10.1371/journal.pmed.1000292.
  8. Rey E., Kahn S.R., David M., Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003; 361(9361): 901-8. https://doi.org/10.1016/S0140-6736(03)12771-7.
  9. Azem F., Many A., Ben Ami I., Yovel I., Amit A., Lessing J.B., Kupferminc M.J. Increased rates of thrombophilia in women with repeated IVF failures. Hum. Reprod. 2004; 19(2): 368-70.
  10. Qublan H.S., Eid S.S., Ababneh H.A., Amarin Z.O., Smadi A.Z., Al-Khafaji F.F., Khader Y.S. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum. Reprod. 2006; 21(10): 2694-8. https://doi.org/10.1093/humrep/del203.
  11. Grandone E., Colaizzo D., Lo Bue A., Checola M.G., Cittadini E., Margaglione M. Inherited thrombophilia and in vitro fertilization implantation failure. Fertil. Steril. 2001; 76(1): 201-2.
  12. Martinelli I., Taioli E., Ragni G., Levi-Setti P., Passamonti S.M., Battaglioli T. et al. Embryo implantation after assisted reproductive procedures and maternal thrombophilia. Haematologica. 2003; 88(7): 789-93.
  13. Qublan H., Amarin Z., Dabbas M., Farraj A.-E., Beni-Merei Z., Al-Akash H. et al. Low-molecular-weight heparin in the treatment of recurrent IVF-ET failure and thrombophilia: a prospective randomized placebo-controlled trial. Hum. Fertil. (Camb.). 2008; 11(4): 246-53. https://doi.org/10.1080/14647270801995431.
  14. Urman B., Ata B., Yakin K., Alatas C., Aksoy S., Mercan R., Balaban B. 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. https://doi.org/10.1093/humrep/dep086.
  15. Клинические рекомендации МЗ РФ «Профилактика венозных тромбоэмболических состояний в акушерстве и гинекологии». М.; 2014.[Clinical recommendations of the Ministry of Health of the Russian Federation «Prevention of venous thromboembolic conditions in obstetrics and gynecology» 2014. (In Russ.)]
  16. Rambaldi M.P., Mecacci F., Guaschino S., Paidas M.J. Inherited and acquired thrombophilias. Reprod. Sci. 2014; 21(2): 167-82. https://doi.org/10.1177/1933719113497282.
  17. Кузнецова И.В., Суханова Г.А. Возможности снижения перинатального и акушерского риска у женщин с тромбофилиями. Эффективная фармакотерапия. 2017; 25: 14-21. [Kuznetsova I.V. MUH. Possibilities for reducing perinatal and obstetric risk in women with thrombophilia. Effective pharmacotherapy. 2017; (25): 14-21. (In Russ.)]
  18. Акиньшина С.В., Макацария А.Д., Бицадзе В.О. Патогенез и профилактика тромбоэмболических осложнений, связанных с использованием вспомогательных репродуктивных технологий. Медицинский совет. 2014; 9: 84-9. [Akinshina S.V., Makatsariya A.D., Bitsadze V.O. Pathogenesis and prevention of thromboembolic complications associated with the use of assisted reproductive technologies. Medical advice. 2014; (9): 84-9. (In Russ.)]
  19. Бицадзе В.О., Акиньшина С.В., Андреева М.Д,. Макацария А.Д. Тромбоэмболические осложнения, связанные с использованием вспомогательных репродуктивных технологий. Синдром гиперстимуляции яичников. Практическая медицина. 2013; 7: 20-31. [Bitsadze V.O., Akinshina S.V., Andreeva M.D., Makatsarya A.D. Thromboembolic complications associated with the use of assisted reproductive technology. Ovarian hyperstimulation syndrome. Practical medicine. 2013; (7): 20-31. (In Russ.)]
  20. Steinvil A., Raz R., Berliner S., Steinberg D.M., Zeltser D., Levran D. et al. Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation. Thromb. Haemost. 2012; 108(6): 1192-7. https://doi.org/10.1160/TH12-06-0381.
  21. Tan X., Yu Z., Sao J., Chen L., Shen Y., Ding J., Shi W. Association between in vitro fertilization outcomes and inherited thrombophilias: a meta-analysis. J. Assist. Reprod. Genet. 2016; 33(8): 1093-8. https://doi.org/10.1007/s10815-016-0726-0.
  22. Di Nisio M., Rutjes A.W.S., Ferrante N., Tiboni G.M., Cuccurullo F., Porreca E. Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis. Blood. 2011; 118(10): 2670-8. https://doi.org/10.1182/blood-2011-03-340216.
  23. Клинические рекомендации МЗ РФ «Вспомогательные репродуктивные технологии и искусственная инсеминация». М.; 2019. [Clinical guidelines of the Ministry of Health of the Russian Federation «Assisted Reproductive Technologies and Artificial Insemination», 2019.(In Russ.)]
  24. ACOG Practice Bulletin No. 197. Inherited thrombophilias in pregnancy. June 2018.
  25. Royal College of Obstetricians and Gynaecologists (RCOG). Reducing the risk of venous thromboembolism during pregnancy and the puerperium. Green-top guideline No. 37a. April 2015.
  26. Chighizola C.B., de Jesus G.R. Antiphospholipid antibodies and infertility. Lupus. 2014; 23(12): 1232-8. https://doi.org/10.1177/0961203314529171.
  27. American College of Obstetricians and Gynecologists (ACOG). Antiphospholipid syndrome. Practice bulletin No.132.December 2012.
  28. Jeve Y.B., Davies W. Evidence-based management of recurrent miscarriages. J. Hum. Reprod. Sci. 2014; 7(3): 159-69. https://doi.org/10.4103/0974-1208.142475.
  29. Rand J.H., Wolgast L.R. Dos and don’ts in diagnosing antiphospholipid syndrome. Hematol. Am. Soc. Hematol. Educ. Progr. 2012; 2012: 455-9. https://doi.org/10.1182/asheducation-2012.1.455.
  30. Макацария А.Д., ред. Антифосфолипидный синдром – иммунная тромбофилия в акушерстве и гинекологии (монография). М.: Триада-Х; 2007. 451 c. [Ed. A.D. Makatsariya, editor. Antiphospholipid syndrome - immune thrombophilia in obstetrics and gynecology (monograph). Moscow, From. 2007. 451 p. (In Russ.)]
  31. Di Rosa R., Ferrero S., Cifani N., Ferri L., Proietta M., Picchianti Diamanti A., Del Porto F. In vitro fertilization and autoimmunity: Evidence from an observational study. Eur. J. Obstet. Gynecol. Reprod. Biol. 2019; 234: 137-42. https://doi.org/10.1016/j.ejogrb.2018.12.042.
  32. Khizroeva J., Makatsariya A., Bitsadze V., Makatsariya N., Khamani N. In vitro fertilization outcomes in women with antiphospholipid antibodies circulation. J. Matern. Fetal Neonatal Med. 2018; Oct 12: 1-11. https://doi.org/10.1080/14767058.2018.1535586.
  33. Royal College of Obstetricians and Gynaecologists (RCOG). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Green-top Guideline No.17. 2011. UpdateFebruary 2017.
  34. Клинические рекомендации МЗ РФ: «Синдром гиперстимуляции яичников: диагностика, лечение, профилактика, интенсивная терапия». М.; 2019. [Clinical recommendations of the Ministry of Health of the Russian Federation: «Ovarian hyperstimulation syndrome: diagnosis, treatment, prevention, intensive therapy», 2019.(InRuss.)]
  35. Spratte J., Bornkessel F., Schütz F., Zygmunt M., Fluhr H. The presence of heparins during decidualization modulates the response of human endometrial stromal cells to IL-1β in vitro. J. Assist. Reprod. Genet. 2016; 33(7): 949-57. https://doi.org/10.1007/s10815-016-0703-7.
  36. Seshadri S., Sunkara S.K., Khalaf Y., El-Toukhy T., Hamoda H. Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis. Reprod. Biomed. Online. 2012; 25(6): 572-84. https://doi.org/10.1016/j.rbmo.2012.08.007.
  37. Akhtar M.A., Sur S, Raine-Fenning N., Jayaprakasan K., Thornton J.G., Quenby S. Heparin for assisted reproduction. Cochrane database Syst. Rev. 2013; (8): CD009452. 0.1002/14651858.CD009452.pub2.
  38. Ata B., Urman B. Thrombophilia and assisted reproduction technology-any detrimental impact or unnecessary overuse? J. Assist. Reprod. Genet. 2016; 33(10): 1305-10. https://doi.org/10.1007/s10815-016-0771-8.
  39. Siristatidis C.S., Basios G., Pergialiotis V., Vogiatzi P. Aspirin for in vitro fertilisation. Cochrane database Syst. Rev. 2016; (11): CD004832. https://doi.org/10.1002/14651858.CD004832.pub4.

Received 22.02.2019

Accepted 19.04.2019

About the Authors

Kraevaya Elizaveta Evgenievna, junior researcher of department of assisted reproductive technology in treating sterilityV.I. Kulakov NMRC OGP, Ministry of Healthcare
of the Russian Federation Tel. +7 (495) 438-25-01.E-mail: e_kraevaya@oparina4.ru 4 Oparin str, 117997, Moscow, Russia
Dolgushina Nataliya Vitalievna, M.D., M.P.H., Head of R&D Department, V.I. Kulakov NMRC OGP, Ministry of Healthcare of the Russian Federation
Tel: +7 (495) 438-49-77.E-mail: n_dolgushina@oparina4.ru
4 Oparin str, 117997, Moscow, Russia

For citation: Kraevaya E.E., Dolgushina N.V. Influence of hereditary and acquired thrombophilia on the outcomes of assisted reproductive technology programs.
Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2019; 8:20-25 (in Russian).
https://dx.doi.org/10.18565/aig.2019.8.20-25

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