Role of miRNA polymorphism in recurrent pregnancy loss: a systematic review and meta-analysis

There are a plethora of publications on the role of miRNA gene polymorphism and its association with recurrent pregnancy loss (RPL), but a lack of uniformity in the studies available due to the variable subject population, heterogeneity and contrary results of significance. Rigorous data mining was done through PubMed, SCOPUS, Cochrane library, Elsevier and Google Scholar to extract the studies of interest published until June 2021. A total of eight SNPs of miRNAs have been included, where ≥2 studies per SNPs were available. Analysis was done on the basis of pooled odds ratios and 95% CI. This is the first meta-analysis on miRNA SNPs in RPL that suggests that rs11614913, rs3746444 and rs2292832 biomarkers may decrease the risk of RPL under different genetic models.

Polymorphisms Within DNA Double-Strand Breaks Repair-Related Genes Contribute to Structural Chromosome Abnormality in Recurrent Pregnancy Loss

Background: Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA.Methods: Fifty-four affected RPL individuals with SCA, 88 affected RPL individuals without SCA, and 84 controls were analyzed. Targeted whole-exome sequencing (WES) was used for screening single nucleotide polymorphisms in six DSBs repair-related genes (EP300, XRCC6, LIG4, XRCC4, PRKDC, and DCLRE1C), and validation was performed by Sanger sequencing. Finally, we detected the frequency of radiation-induced chromosome translocations in no SCA samples with significant polymorphisms by fluorescence in situ hybridization (FISH).Results: A total of 35 polymorphisms have been identified and confirmed. Frequencies of EP300 rs20551, XRCC6 rs132788, and LIG4 rs1805388 were significantly different between SCA RPL and no SCA RPL (p = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different (p = 0.017, 0.028, and 0.029 respectively). Moreover, the frequency of the G allele at rs20551 locus, the T allele at rs132788 locus and the A allele at rs1805388 locus was significantly higher in SCA RPL than no SCA RPL (OR = 3.227, p = 0.005; OR = 1.978, p = 0.008 and OR = 1.769, p = 0.036 respectively) and controls (OR = 7.130, p = 0.000; OR = 2.157, p = 0.004; OR = 2.397, p = 0.003 respectively). Additionally, the frequency of radiation-induced translocation in no SCA samples with rs20551, rs132788 or rs1805388 was significantly higher compared with the wild type samples (p = 0.015, 0.012, and 0.007 respectively).Conclusion: Our results suggest that rs20551, rs132788, and rs1805388 might be associated with the risk of SCA. Larger scales of genetic variations studies and functional experiments are necessary to further confirm these findings.

Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

Noninvasive Chromosome Screening for Evaluating the Clinical Outcomes of Patients With Recurrent Pregnancy Loss or Repeated Implantation Failure

Background: This retrospective cohort study determines whether noninvasive chromosome screening (NICS) for aneuploidy can improve the clinical outcomes of patients with recurrent pregnancy loss (RPL) or repeated implantation failure (RIF) in assisted reproductive technology.Methods: A total of 273 women with a history of RPL or RIF between 2018 and 2021 were included in this study. We collected data of all oocyte retrieval cycles and single blastocyst resuscitation transfer cycles.Results: For the RPL patients, NICS reduced the miscarriages rate per frozen embryo transfer (FET), improved the ongoing pregnancies rate and live birth rate: 17.9% vs 42.6%, adjusted OR 0.39, 95% CI 0.16–0.95; 40.7% vs 25.0%, adjusted OR 2.00, 95% CI 1.04–3.82; 38.9% vs 20.6%, adjusted OR 2.53, 95% CI 1.28–5.02, respectively. For the RIF patients, the pregnancy rates per FET in the NICS group were significantly higher than in the non-NICS group (46.9% vs. 28.7%, adjusted OR 2.82, 95% CI 1.20–6.66).Conclusions: This study demonstrated that selection of euploid embryos through NICS can reduce the miscarriage rate of patients with RPL and improve the clinical pregnancy rate of patients with RIF. Our data suggested that NICS could be used as a diagnostic test in clinical practice.

Causes and Management of Recurrent Pregnancy Loss, a Review

Recurrent Pregnancy Loss (RPL) is defined as two or more consecutive failed clinical pregnancies verified by ultrasound or histopathology. It is an important reproductive health issue, affecting 2%–5% of women. Up to one half of all cases of RPL have no identifiable cause. Etiology of the RPL is linked to several genetic, environmental, endocrinal, and anatomic factors which all will be discussed in this article. Treatment of RPL depends on the underlying cause behind it, and thus diagnosis and identifying of such factors plays major role into treating it. Lifestyle changes also is encouraged. Stress, smoking, drinking cessation, and weight loss can be all helpful. In this article we’ll be looking at RPL causes, and management.

The association between female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study

Objective To study the associations of endometrial and vaginal microbiota with recurrent pregnancy loss (RPL). Design A nested case-control study. Setting Helsinki University Hospital, Finland. Population Women with two or more consecutive pregnancy losses (n=47) and healthy control women without a history of pregnancy loss (n=39). Methods The endometrial and vaginal microbiota compositions, analysed using 16S rRNA gene amplicon sequencing, were compared between RPL women and controls, and between individual vaginal and endometrial samples. The mycobiota composition was analysed using internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The models were adjusted for confounding variables BMI, age, and parity, and FDR-corrected P-values (q-values) were used to define nominal statistical significance at q < 0.05. Main outcome measures Mean relative microbial abundances. Results Lactobacillus crispatus was less abundant in the RPL endometrial samples compared to controls (mean relative abundance 17.2% vs. 45.6%, q = 0.04). Gardnerella vaginalis was more abundant in RPL women than in controls in both endometrial (12.4% vs. 5.8%, q < 0.001) and vaginal samples (8.7% vs. 5.7%, q < 0.01). The individual vaginal and endometrial microbial composition correlated strongly (R = 0.85, P < 0.001). Fungi were detected in 22% of the endometrial and 36% of the vaginal samples. Conclusions Unfavourable reproductive tract microbiota was associated with RPL and may represent a novel risk factor for pregnancy losses.