Comparison of Two Preventive Treatments for Patients with Recurrent Miscarriages Carrying a C677T Methylenetetrahydrofolate Reductase Mutation: 5-year Experience

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2017 Jul 14

PMID 28703660

Citations 3

Authors

Philippe Merviel

Rosalie Cabry

Emmanuelle Lourdel

Segolene Lanta

Carole Amant

Henri Copin

Moncef Benkhalifa

Affiliations

Soon will be listed here.

Abstract

Objective To investigate the effect of anticoagulant treatment on pregnancy outcomes in patients with previous recurrent miscarriages (RM) who carry a methylenetetrahydrofolate reductase ( MTHFR) gene mutation. Methods In this longitudinal retrospective study, patients with RM were treated during pregnancy with either: (i) 100 mg/day aspirin and 5 mg/day folic acid (group 1); or the same protocol plus 0.4 mg/day enoxaparin (group 2). An age-matched group of triparous women without RM or thrombophilia was used as the control group (group 3). Results This study enrolled 246 women with RM (123 per treatment group) and age-matched controls ( n = 117). The delivery rate was significantly lower in group 1 than group 2 (46.3% versus 79.7%, respectively). The miscarriage rate was significantly lower in group 2 compared with group 1 (20.3% versus 51.2%, respectively). In the control group 3, the delivery rate was 86.3% and the miscarriage rate was 12.8%. Conclusion Treatment with low-dose aspirin, enoxaparin and folic acid was the most effective therapy in women with RM who carried a C677T MTHFR mutation.

Citing Articles

Influence of Socioeconomic Status on the Association Between Pregnancy Complications and Premature Coronary Artery Disease: Linking Three Cohorts.

Khoja A, Andraweera P, Tavella R, Gill T, Dekker G, Roberts C Womens Health Rep (New Rochelle). 2024; 5(1):120-131.

PMID: 38404672 PMC: 10890942. DOI: 10.1089/whr.2023.0092.

MTHFR 1298A>C Substitution is a Strong Candidate for Analysis in Recurrent Pregnancy Loss: Evidence from 14,289 Subjects.

Mehta P, Vishvkarma R, Singh K, Rajender S Reprod Sci. 2021; 29(4):1039-1053.

PMID: 33742421 DOI: 10.1007/s43032-021-00530-5.

Safety and Efficacy of Enoxaparin in Pregnancy: A Systematic Review and Meta-Analysis.

Jacobson B, Rambiritch V, Paek D, Sayre T, Naidoo P, Shan J Adv Ther. 2019; 37(1):27-40.

PMID: 31673991 PMC: 6979442. DOI: 10.1007/s12325-019-01124-z.

References

Morales-Machin A, Borjas-Fajardo L, Quintero J, Zabala W, Alvarez F, Delgado W . [C677T polymorphism of the methylentetrahydrofolate reductase gene as risk factor in women with recurrent abortion]. Invest Clin. 2009; 50(3):327-33. View

Kosmas I, Tatsioni A, Ioannidis J . Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J Hypertens. 2004; 22(9):1655-62. DOI: 10.1097/00004872-200409000-00004. View

Regan L, Braude P, Trembath P . Influence of past reproductive performance on risk of spontaneous abortion. BMJ. 1989; 299(6698):541-5. PMC: 1837397. DOI: 10.1136/bmj.299.6698.541. View

Reginald P, BEARD R, Chapple J, Forbes P, LIDDELL H, Mowbray J . Outcome of pregnancies progressing beyond 28 weeks gestation in women with a history of recurrent miscarriage. Br J Obstet Gynaecol. 1987; 94(7):643-8. DOI: 10.1111/j.1471-0528.1987.tb03168.x. View

Powers R, Dunbar M, Gallaher M, Roberts J . The 677 C-T methylenetetrahydrofolate reductase mutation does not predict increased maternal homocysteine during pregnancy. Obstet Gynecol. 2003; 101(4):762-6. DOI: 10.1016/s0029-7844(02)03120-4. View

Badawy A, Khiary M, Sherif L, Hassan M, Ragab A, Abdelall I . Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology. J Obstet Gynaecol. 2008; 28(3):280-4. DOI: 10.1080/01443610802042688. View

Zetterberg H . Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications. Reprod Biol Endocrinol. 2004; 2:7. PMC: 356929. DOI: 10.1186/1477-7827-2-7. View

Mahjoub T, Mtiraoui N, Tamim H, Hizem S, Finan R, Nsiri B . Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages. Am J Hematol. 2005; 80(1):12-9. DOI: 10.1002/ajh.20419. View

Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe G . Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006; 132(2):171-96. DOI: 10.1111/j.1365-2141.2005.05847.x. View

10.

Stephenson M . Management of recurrent early pregnancy loss. J Reprod Med. 2006; 51(4):303-10. View

11.

Cao Y, Xu J, Zhang Z, Huang X, Zhang A, Wang J . Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis. Gene. 2012; 514(2):105-11. DOI: 10.1016/j.gene.2012.10.091. View

12.

Bick R, Hoppensteadt D . Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update. Clin Appl Thromb Hemost. 2005; 11(1):1-13. DOI: 10.1177/107602960501100101. View

13.

Brenner B, Bar J, Ellis M, Yarom I, Yohai D, Samueloff A . Effects of enoxaparin on late pregnancy complications and neonatal outcome in women with recurrent pregnancy loss and thrombophilia: results from the Live-Enox study. Fertil Steril. 2005; 84(3):770-3. DOI: 10.1016/j.fertnstert.2005.03.048. View

14.

Poddar R, Sivasubramanian N, Dibello P, Robinson K, Jacobsen D . Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation. 2001; 103(22):2717-23. DOI: 10.1161/01.cir.103.22.2717. View

15.

Mtiraoui N, Zammiti W, Ghazouani L, Braham N, Saidi S, Finan R . Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction. 2006; 131(2):395-401. DOI: 10.1530/rep.1.00815. View

16.

Nelen W, Steegers E, Eskes T, Blom H . Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet. 1997; 350(9081):861. DOI: 10.1016/S0140-6736(97)24038-9. View

17.

Altomare I, Adler A, Aledort L . The 5, 10 methylenetetrahydrofolate reductase C677T mutation and risk of fetal loss: a case series and review of the literature. Thromb J. 2007; 5:17. PMC: 2098747. DOI: 10.1186/1477-9560-5-17. View

18.

Merviel P, Carbillon L, Challier J, Rabreau M, Beaufils M, Uzan S . Pathophysiology of preeclampsia: links with implantation disorders. Eur J Obstet Gynecol Reprod Biol. 2004; 115(2):134-47. DOI: 10.1016/j.ejogrb.2003.12.030. View

19.

Quere I, Mercier E, Bellet H, Janbon C, Mares P, Gris J . Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril. 2001; 75(4):823-5. DOI: 10.1016/s0015-0282(01)01678-8. View

20.

Pozharny Y, Lambertini L, Ma Y, Ferrara L, Litton C, Diplas A . Genomic loss of imprinting in first-trimester human placenta. Am J Obstet Gynecol. 2010; 202(4):391.e1-8. DOI: 10.1016/j.ajog.2010.01.039. View