Abstract
Purpose
The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population.
Methods
A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G → A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss.
Results
Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient.
Conclusions
Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated.
Similar content being viewed by others
References
Kovalevsky G, Gracia CR, Berlin JA, Sammel MD, Barnhart KT. Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med. 2004;164(5):558–63. doi:10.1001/archinte.164.5.558.
Coulam CB, Jeyendran RS. Thrombophilic gene polymorphisms are risk factors for unexplained infertility. Fertil Steril. 2009;91(4 Suppl):1516–7. doi:10.1016/j.fertnstert.2008.07.1782.
Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901–8. doi:10.1016/S0140-6736(03)12771-7.
Grandone E, Colaizzo D, Lo Bue A, Checola MG, Cittadini E, Margaglione M. Inherited thrombophilia and in vitro fertilization implantation failure. Fertil Steril. 2001;76(1):201–2.
Azem F, Many A, Ben Ami I, Yovel I, Amit A, Lessing JB, et al. Increased rates of thrombophilia in women with repeated IVF failures. Hum Reprod. 2004;19(2):368–70.
Qublan HS, Eid SS, Ababneh HA, Amarin ZO, Smadi AZ, Al-Khafaji FF, et al. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum Reprod. 2006;21(10):2694–8. doi:10.1093/humrep/del203.
Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol. 2006;55(5):360–8. doi:10.1111/j.1600-0897.2006.00376.x.
Martinez-Zamora MA, Creus M, Tassies D, Reverter JC, Civico S, Carmona F, et al. Reduced plasma fibrinolytic potential in patients with recurrent implantation failure after IVF and embryo transfer. Hum Reprod. 2011;26(3):510–6. doi:10.1093/humrep/deq369.
Martinelli I, Taioli E, Ragni G, Levi-Setti P, Passamonti SM, Battaglioli T, et al. Embryo implantation after assisted reproductive procedures and maternal thrombophilia. Haematologica. 2003;88(7):789–93.
Vaquero E, Lazzarin N, Caserta D, Valensise H, Baldi M, Moscarini M, et al. Diagnostic evaluation of women experiencing repeated in vitro fertilization failure. Eur J Obstet Gynecol Reprod Biol. 2006;125(1):79–84. doi:10.1016/j.ejogrb.2005.08.001.
Simur A, Ozdemir S, Acar H, Colakoglu MC, Gorkemli H, Balci O, et al. Repeated in vitro fertilization failure and its relation with thrombophilia. Gynecol Obstet Investig. 2009;67(2):109–12. doi:10.1159/000165776.
Gopel W, Ludwig M, Junge AK, Kohlmann T, Diedrich K, Moller J. Selection pressure for the factor-V-Leiden mutation and embryo implantation. Lancet. 2001;358(9289):1238–9. doi:10.1016/S0140-6736(01)06354-1.
Rudick B, Su HI, Sammel MD, Kovalevsky G, Shaunik A, Barnhart K. Is factor V Leiden mutation a cause of in vitro fertilization failure? Fertil Steril. 2009;92(4):1256–9. doi:10.1016/j.fertnstert.2009.03.089.
van Dunne FM, Doggen CJ, Heemskerk M, Rosendaal FR, Helmerhorst FM. Factor V Leiden mutation in relation to fecundity and miscarriage in women with venous thrombosis. Hum Reprod. 2005;20(3):802–6. doi:10.1093/humrep/deh640.
D’Elia PQ, dos Santos AA, Bianco B, Barbosa CP, Christofolini DM, Aoki T. MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women. Reprod Biomed Online. 2014;28(6):733–8. doi:10.1016/j.rbmo.2014.02.005.
Di Nisio M, Rutjes AW, Ferrante N, Tiboni GM, Cuccurullo F, Porreca E. Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis. Blood. 2011;118(10):2670–8. doi:10.1182/blood-2011-03-340216.
International HapMap C, Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–8. doi:10.1038/nature09298.
Michelson AD, Furman MI, Goldschmidt-Clermont P, Mascelli MA, Hendrix C, Coleman L, et al. Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists. Circulation. 2000;101(9):1013–8.
Cooke GE, Bray PF, Hamlington JD, Pham DM, Goldschmidt-Clermont PJ. PlA2 polymorphism and efficacy of aspirin. Lancet. 1998;351(9111):1253. doi:10.1016/S0140-6736(05)79320-X.
Acknowledgments
Ferring Pharmaceuticals (Saint-Prex, Switzerland) financially supported this study with an unrestricted research grant. The authors greatly appreciated the help of Batsal Devkota and Deanne Taylor for assistance with the database queries.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors of this paper have no conflicts of interest, financial or otherwise, to declare.
Additional information
Clinical Trial Number (ClinicalTrials.gov): NCT01223092
Capsule
Nine thrombophilic single nucleotide polymorphisms lack a significant effect on positive pregnancy test, clinical pregnancy, embryo implantation, pregnancy loss, and live birth in fresh non-donor IVF cycles.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplemental Table 1
Custom TaqMan SNP Genotyping Assay primers and probes (DOC 55 kb)
Supplemental Table 2
Genotype frequencies compared with HapMap CEU population (DOC 57 kb)
Rights and permissions
About this article
Cite this article
Patounakis, G., Bergh, E., Forman, E.J. et al. Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients. J Assist Reprod Genet 33, 67–73 (2016). https://doi.org/10.1007/s10815-015-0606-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-015-0606-z