Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure
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To evaluate the association of two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with recurrent miscarriage (RM) and repeated implantation failure (RIF)
The study comprised of 521 patients, with a history of RM (n = 370) or RIF (n = 151). One hundred forty-four women with fallopian tube blockages who had successfully conceived after the first in vitro fertilization embryo transfer treatment served as the control group. The MTHFR alleles, genotypes, and haplotypes were assessed in different groups.
There was no difference in allele frequency and distribution of MTHFR polymorphisms between case and control patients. The 1298AA genotype was represented in a higher frequency, and 1298AC genotype was significantly lower in subfertile group when compared to the control group. A significant relationship was found between the 1298AC genotype and the RIF subgroup. The haplotype 677CC/1298AA was overrepresented in the RM subgroup (> 2 times) and haplotype 677CC/1298AC was underrepresented in the RIF subgroup (P < 0.05). Nevertheless, these two haplotypes were not connected to fertilization and embryo cleavage rates.
Our findings indicate that the MTHFR gene polymorphism might play a role in the etiology of patients with RM or RIF. No adverse effects of different MTHFR haplotypes on embryo development were detected. Further studies on the biological role are needed to better understand the susceptibility to pregnancy complications.
KeywordsMTHFR Polymorphism Genotype Repeated implantation failure Recurrent miscarriage
repeated implantation failure
in vitro fertilization
We are very grateful to all participants in this study and we thank all the clinical staff. We also thank all the members of the Zhang and Zeng group for their interesting discussions, helpful suggestions, and technical support.
YOZ and YZ: supervised and supported the study. YCZ: designed and wrote the manuscript. GGL: revised the manuscript. THW: data collection. LJY: PCR assay. All authors read and approved the final manuscript.
This study was supported by the National Natural Science Foundation of China (No. 31371315, 2014; No. 81601279, 2016) and International Cooperation Grant of Shenzhen (No. GJHZ20140416153718941, 2014).
Compliance with ethical standards
Ethics approval and consent to participate
The research project met our ethics criteria and was approved and performed strictly according to the protocols. Informed consent was obtained from all couples prior to the study.
Consent for publication
The ethical committee reviewed the manuscript and consent for publication.
The authors declare that they have no conflicts of interest.
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