Top

Journal of Assisted Reproduction and Genetics

Published in:

01-01-2016 | Genetics

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients

Authors: George Patounakis, Eric Bergh, Eric J. Forman, Xin Tao, Agnieszka Lonczak, Jason M. Franasiak, Nathan Treff, Richard T. Scott Jr.

Published in: Journal of Assisted Reproduction and Genetics | Issue 1/2016

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.

Available only for authorised users

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMed

10.

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.PubMedCrossRef

11.

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.CrossRef

12.

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.PubMedCrossRef

13.

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.PubMedCrossRef

14.

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.PubMedCrossRef

15.

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.PubMedCrossRef

16.

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.PubMedCrossRef

17.

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.CrossRef

18.

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.PubMedCrossRef

19.

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.PubMedCrossRef

Title: Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients
Authors: George Patounakis
Eric Bergh
Eric J. Forman
Xin Tao
Agnieszka Lonczak
Jason M. Franasiak
Nathan Treff
Richard T. Scott Jr.
Publication date: 01-01-2016
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 1/2016
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-015-0606-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit

What maintains the high intra-follicular estradiol concentration in pre-ovulatory follicles?

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

Quantitative and qualitative trophectoderm grading allows for prediction of live birth and gender

Discriminately disposable after single use: the trophectoderm and its derivatives

Does reducing gamete co-incubation time improve clinical outcomes: a retrospective study