Common Methylenetetrahydrofolate Reductase Polymorphisms (A1298C & C677T) in Ectopic Trophoblasts and Methotrexate Treatment Failure in Tubal Pregnancies

Abstract

Objectives: The success rate of methotrexate (MTX) therapy varies among tubal ectopic pregnancies. Common methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T&A1298C) have been suggested to alter MTX effect. This study aimed to assess and compare MTX treatment failure rates with respect to MTHFR polymorphisms in trophoblasts of ectopic tubal pregnancies. Material and methods: A retrospective chart review of tubal ectopic pregnancies was conducted and 34 eligible cases were found. Paraffinized blocks of ectopic trophoblastic tissues were retrieved from the archives of pathology department. Common MTHFR polymorphisms were studied on microdissected trophoblastic tissues. Sixteen cases with history of failed MTX therapy (study group) and 18 control cases were compared for their pertinent clinical characteristics and common MTHFR polymorphisms (C677T&A1298) data. Results: In the study group, there were 8 (50%) C677T single nucleotide polymorphisms (SNP) and 9 (56.7%) A1298C SNP. Polymorphism rates were not found to be different between two groups for neither polymorphism (p > 0.05 for both). Number of compound heterozygotes was 3 (18.7%) in study group and 5 (27.7%) in controls (p = 0.693). In addition, MTHFR polymorphism presence seemed to have no effect on interval serum β-hCG concentration change in MTX-fail group (p=0.693). Conclusions: Our data implied that common MTHFR polymorphisms of ectopic trophoblastic tissue are not associated with MTX failure in patients with tubal pregnancies. Additionally, serum β-hCG concentration changes caused by MTX treatment and studied MTHFR polymorphisms are likely independent.

Contribution of genetic polymorphism of methylene tetrahydrofolate reductase on the effect of methotrexate in ectopic pregnancy patients

“…Chen Y et al concluded that C677T polymorphism of MTHFR predicts nonresponse and adverse effects of MTX in juvenile idiopathic arthritis . However, two studies implied that MTHFR C677T was not associated with MXT failure and β ‐hCG concentration changes during MTX treatment in patients with tubal EP . Interestingly, our results showed that CC carriers had a lower success rate than CT and TT carriers by first MTX injection and another dosage of MTX treatment.…”