Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss

At present, the etiology and pathogenesis of recurrent early pregnancy loss (REPL) are not completely clear. Therefore, identifying the underlying diagnostic and prognostic biomarkers of REPL can provide new ideas for the diagnosis and treatment of REPL. The chip data of REPL (GSE63901) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module for studying the relationship between gene modules and clinical features. In addition, functional analysis of hub genes in modules of interest was performed. A total of 23 co-expression modules were identified, two of which were most significantly associated with three clinical features. The MEbrown module was positively correlated with cyclin E level and the out-of-phase trait while the MEred module was positively correlated with the effect of progesterone. We identified 17 hub genes in the MEred module. The functional enrichment analysis indicated that such hub genes were mainly involved in pathways related to cellular defense response and natural killer (NK) cell-mediated cytotoxicity. In the MEbrown module, we identified 19 hub genes, which were mainly enriched in cell adhesion molecule production, regulation of cellular response to growth factor stimulus, epithelial cell proliferation, and transforming growth factor-β (TGF-β) signaling pathway. In addition, the hub genes were validated by using other datasets and three true hub genes were finally obtained, namely DOCK2 for the MEred module, and TRMT44 and ERVMER34-1 for the MEbrown module. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of REPL.

An observational study of effect of Mullerian anomalies on pregnancy

Background: Mullerian anomalies occur in approximately 3-4% of fertile and infertile women, 5–10% of women with recurrent early pregnancy loss, and up to 25% of women with late first or second-trimester pregnancy loss or preterm delivery. However, due to low prevalence rate and asymptomatic course of the anomalies, Mullerian anomalies remain underdiagnosed and often overlooked as a possible cause of recurrent pregnancy failures, preterm deliveries, IUGR and low birth weight.Methods: Total of 30 cases of Mullerian anomalies with pregnancy, prior diagnosed or incidental during LSCS, were studied for complications during pregnancy, history of gynecological complaints and rate of diagnosis with routine imaging technique.Results: Septate uterus was the most common anomaly seen in this study (36.6%).56.6% were diagnosed incidentally during LSCS despite the fact 26.6% of cases had history of 2 or more abortions and 30% had some or other gynecological complaints previously. 10% of pregnancies ended in abortions, 20% had preterm delivery, 36.6% had malpresentations and there was case of rupture uterus (03.3%).Conclusions: Mullerian anomalies are often asymptomatic or have subtle gynecological symptoms which are often missed by both patient and gynecologists. It is observed that due to the asymptomatic course of Mullerian anomalies, invasive nature of HSG and lack of 1.5 Tesla MRI at many institutes leads to low rate of diagnosis of Mullerian anomalies. Pregnancy with Mullerian anomalies often have preterm delivery, IUGR and malpresentation, so, require proper counselling and close monitoring during antenatal period.

Observational study of HSG with laparoscopic correlation in infertility patients

Background: Uterine abnormalities contribute to 10% of infertility cases and 50% of women with recurrent early pregnancy loss whereas fallopian tube abnormalities contribute to 20% of such cases.Methods: Total 61 patients of infertility and subfertility undergoing evaluation and treatment at our centre were selected for HSG. Total 25 patients from this group have undergone diagnostic laparoscopy, their findings were correlated with HSG findings retrospectively.Results: All the patients in the study group were either primary or secondary infertility patients. Of the 61 patients of infertility, 49 were in primary infertility group and 12 were in secondary infertility group. The age of patients was between 23 and 35 years. The average duration of primary infertility was 5 years and secondary infertility was 3.5years. Total 61 patients underwent HSG, 42(68.8%) patients had normal findings and 19(31.14%) patients had abnormal findings. In abnormal findings 4(6.55%) were Mullerian abnormalities and 15(24.59%) were either unilateral or bilateral tubal block. Total 25 patients underwent diagnostic laparoscopy out of 61 patients. The sensitivity of HSG was 90% and specificity was 60 % with positive predictive value of 60% and negative predictive value of 90% as compared to diagnostic laparoscopy. Tubal block was defined as any form of tubal occlusion detected at HSG and finally confirmed on laparoscopy. In our laparoscopy findings, peri-adnexal adhesions were found in 5 (20%) of the blocked tubes on laparoscopy. Endometriosis was detected in 1 (4%) of the blocked tubes and suspected intra-tubal block in 2 (8%).Pelvic inflammatory disease was found to contribute in 3 (12%).Conclusions: HSG demonstrates high sensitivity in our study. So, it should be used as the initial investigation for identifying uterine abnormality and tubal patency. As the specificity is less, we suggest that laparoscopy is necessary to recognize those cases of tubal block, which were unrecognized or wrongly recognized on HSG. In addition, the patients who were found to have tubal block on HSG, laparoscopy helps in finding the cause of infertility like existence of peritubal adhesions and endometriosis that can guide appropriate therapy.