Correlation between sperm DNA fragmentation and methylation in male partners of couples with idiopathic recurrent pregnancy loss.

With ∼50% recurrent pregnancy loss cases being termed idiopathic (iRPL), understanding of contribution of male factors to iRPL is still lacking. Higher prevalence of sperm DNA fragmentation index (DFI) and lower sperm 5-methylcytosine (5-mC) levels have been previously reported in male partners of iRPL couples and shed light on importance of the male gamete in maintenance of a successful pregnancy. The present study aimed to determine the serum sex steroid hormone levels, sperm DFI and 5-mC and correlation between them in male partners of fertile and iRPL couples. Further, correlation between sperm DFI and 5-mC with semen parameters and paternal age in both groups were determined. 36 male partners of fertile couples and 45 male partners of women experiencing iRPL were enrolled for this study and semen and blood samples were collected. Serum testosterone and estradiol levels were measured by ELISA; sperm DFI and global 5-mC were determined by TUNEL assay and ELISA respectively. Significantly higher serum testosterone levels were noted in the iRPL group (p = 0.028). Incidence of sperm DNA fragmentation was found to be higher in the iRPL study group but with no significance difference. No significant differences in sperm 5-mC values were noted. Upon correlation analysis within both groups, strong significant negative correlation of sperm DFI % and 5-mC % was observed in the control group (p < 0.001) but not the iRPL group (p = 0.249). Hence, we infer that with lower 5-mC levels in sperm genome, there is a higher incidence of sperm DFI in fertile men. However, this trend is not noted in men of iRPL group which could possibly be due to other underlying epigenetic alterations in genomic regions probably unsusceptible to fragmentation. On the other hand, no significant correlations of semen parameters, testosterone, estradiol and paternal age with sperm DFI and 5-mC were noted in both groups.

Susceptibility loci identified in Han Chinese influence genetic predisposition of PCOS in Indian women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by a broad spectrum of reproductive and metabolic perturbations, necessitating early timely diagnosis and management. PCOS is a multigenic disorder and ample evidence from family based, candidate gene and genome-wide association studies (GWAS) has implicated genetic factors in development and progression of PCOS. The first GWASs in Han Chinese population revealed prominent gene loci to be strong contenders in the etiopathogenesis of PCOS. However, different ethnic and geographical settings impact the genetic association pattern of PCOS. METHODS AND RESULTS: In the current case-control replication study, we have genotyped previously identified polymorphisms viz. rs2479106 and rs10818854 of DENND1A and rs13405728 of LHCGR, rs4385527 and rs3802457 of c9orf3, rs705702 of RAB5B and rs1894116 of YAP1 in control (N = 247) and PCOS (N = 504) women by Sanger sequencing, and their association with PCOS susceptibility and its related traits was investigated. We found significant association of rs4385527 of c9orf3 and rs1894116 of YAP1 with decreased and increased PCOS susceptibility respectively in non-hyperandrogenic women. Trend towards association was also noted for rs2479106 of DENND1A and rs705702 of RAB5B. Additionally, polymorphisms also showed association with metabolic and androgen related traits in both controls and hyper- and non-hyperandrogenic women with PCOS. CONCLUSIONS: Thus, this study shows that some, but not all polymorphisms previously identified in Han Chinese women, could contribute to the genetic pathophysiology of PCOS in Indian women, accentuating essentiality of conducting replication studies to elucidate the genetic predisposition profile of PCOS.

Investigating the association of previously identified genome-wide significant loci (rs10739076 and rs1784692) with PCOS susceptibility and its related traits in Indian women.

OBJECTIVE(S): Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy with an enigmatic etiology. Hallmark features include irregular menstrual cycles, insulin resistance and hyperandrogenemia and affected women are prone to development of adverse reproductive and cardiometabolic outcomes like anovulatory infertility, impaired glucose tolerance, type 2 diabetes, dyslipidemia, metabolic syndrome and cardiovascular disease. Genetic underpinnings of PCOS have been investigated extensively using genome-wide association studies, which have led to the identification of several novel susceptibility loci. However, as ethnic diversity contributes to phenotypic and genetic heterogeneity, we undertook the first genetic association study to determine the association of rs10739076 of PLGRKT and rs1784692 of ZBTB16 with PCOS susceptibility and its related traits in Indian women. STUDY DESIGN: The present case-control study comprised 497 women with PCOS diagnosed according to the Rotterdam criteria and 233 age matched healthy women as controls. All participants were characterized in terms of anthropometric, hormonal and metabolic parameters and the variants were investigated by direct sequencing. Genotypic and genotype-phenotype association of these variants with PCOS susceptibility and its related biochemical and hormonal traits was analyzed with appropriate statistical tests. RESULTS: The genotypic and allelic frequencies of rs1784692 of ZBTB16 were significantly decreased in lean women with PCOS only, and this variant was associated with lowered insulin levels, HOMA-IR, LH:FSH ratio along with increased ApoA1 levels and QUICKI in them. Although, the PLGRKT variant, rs10739076, showed similar frequency distribution in both lean and obese groups, it was found to be associated with reduced fasting glucose in all women with PCOS. CONCLUSION(S): To the best of our knowledge, this is the first study to demonstrate that ZBTB16 variant showed significant association with reduced PCOS susceptibility in lean rather than obese Indian women, highlighting the impact of obesity on determining genetic predisposition to PCOS in Indian women. In contrast, PLGRKT variant did not influence PCOS risk in lean or obese women. Importantly, both variants exerted a protective effect on glucose metabolism, insulin resistance, gonadotropin and lipid levels in women with PCOS. Determination of susceptibility variants for PCOS demand population specific replication studies to ascertain best candidate loci for PCOS.

Relevance of augmented kisspeptin signaling through H364 KISS1R in central precocious puberty.

Understanding the pathophysiology of idiopathic central precocious puberty (ICPP) is essential, in view of its consequences on reproductive health and metabolic disorders in later life. Towards this, estimation of circulating levels of the neuropeptides, viz; Kisspeptin (Kp-10), Neurokinin B (NKB) and Neuropeptide Y (NPY), acting upstream to Gonadotropin-Releasing Hormone (GnRH), has shown promise. Insights can also be gained from functional studies on genetic variations implicated in ICPP. This study investigated the pathophysiology of ICPP in a girl by exploring the therapeutic relevance of the circulating levels of Kp-10, NKB, NPY and characterizing the nonsynonymous KISS1R variant, L364H, that she harbours, in a homozygous condition. Plasma levels of Kp-10, NKB and NPY before and after GnRH analog (GnRHa) treatment, were determined by ELISA. It was observed that GnRHa treatment resulted in suppression of circulating levels of Kp-10, NKB and NPY. Further, the H364 variant in KISS1R was generated by site directed mutagenesis. Post transient transfection of either L364 or H364 KISS1R variant in CHO cells, receptor expression was ascertained by western blotting, indirect immunofluorescence and flow cytometry. Kp-10 stimulated signalling response was also determined by phospho-ERK and inositol phosphate production. Structure-function studies revealed that, although the receptor expression in H364 KISS1R was comparable to L364 KISS1R, there was an enhanced signalling response through this variant at high doses of Kp-10. Thus, elevated levels of Kp-10, acting through H364 KISS1R, contributed to the manifestation of ICPP, providing further evidence that dysregulation of Kp-10/KISS1R axis impacts the onset of puberty.

DNA methylation biomarkers to identify epigenetically abnormal spermatozoa in male partners from couples experiencing recurrent pregnancy loss.

Previously, we showed that DNA methylation defects in spermatozoa from male partners of couples undergoing recurrent pregnancy loss (RPL) could be a contributing paternal factor. In the present study, we aimed to determine whether the methylation levels of selected imprinted genes can be used as diagnostic markers to identify epigenetically abnormal spermatozoa sample in these cases. The methylation levels of selected imprinted genes in spermatozoa, which were previously found to be differentially methylated, were combined into a probability score (between 0-1) using multiple logistic regression. Different combinations of these genes were investigated using Receiver Operating Characteristic analysis, and the threshold values were experimentally validated in an independent cohort of 38 control and 45 RPL spermatozoa samples. Among the different combinations investigated, a combination of five imprinted genes comprising IGF2-H19 DMR, IG-DMR, ZAC, KvDMR, and PEG3 (AUC = 0.88) with a threshold value of 0.61 was selected with a specificity of 90.41% and sensitivity of 70%. The results from the validation study indicated that 97% of the control samples had probability scores below this threshold, whereas 40% of the RPL samples were above this threshold with a post-hoc power of 97.8%. Thus, this combination can correctly classify control samples and potentially identify epigenetically abnormal spermatozoa samples in the male partners of couples undergoing RPL. We propose that the combined DNA methylation levels of these imprinted genes can be used as a diagnostic tool to identify spermatozoa samples with epigenetic defects which could contribute to the pathophysiology of RPL and the couple could be counselled appropriately.

Mapping the vaginal microbiota variations in women from a community clinic in Mumbai, India.

PURPOSE: The vaginal microbiome contributes significantly to women's reproductive health and fluctuates due to various physiological and pathological factors. The study's objective is to map the vaginal microbiome of non-pregnant women and evaluate variations based on various potential factors influencing vaginal milieu. METHODS: Fifty-two sexually active, non-pregnant women between 18 and 45 years were recruited from a community clinic and clinical history was recorded. Vaginal swabs were collected to assess the vaginal microbiome by sequencing the V3-V4 region of the 16S rRNA using the Illumina HiSeq platform, followed by data analysis with QIIME 2. Vaginal milieu was assessed by Nugent score and profiling cytokines in the cervico-vaginal lavage. RESULTS: Lactobacillus iners (34.3%) were the most abundant species in all women. Significant changes in abundance of genera (Lactobacillus, Prevotella and Anaerococcus), expression of pro-inflammatory cytokine IFN-γ and changes in alpha and beta diversity was observed in women having asymptomatic bacterial vaginosis (BV). Differences in beta diversity were seen between healthy women and women exhibiting presence of Candida spp. Variations in the abundance of genera (Lactobacillus, Bifidobacterium, Porphyromonas) were observed in women who had delivery less than twelve months back, probably as more of these women (50%, 53.7%) had higher abnormal Nugent score. CONCLUSION: Lactobacillus iners was the most prevalent vaginal species in women from a Mumbai community clinic. Maximum variations in the vaginal microbiome characterized by a perturbation of the Lactobacillus predominant vaginal microbiota are seen in those women who have asymptomatic BV and childbirth within last twelve months.

Incidence & factors influencing maternal near miss events in tertiary hospitals of Maharashtra, India.

Background & objectives: Government of India (GoI) released operational guidelines for maternal near miss-review (MNM-R) in 2014 for use by programme managers of public health system to assist them for conducting MNM-R. The objective of the present study was to review the incidence and factors influencing MNM events in two tertiary hospitals of Maharashtra, India, as per the operational guidelines of the GoI released in 2014 and identify delays based on three-delay model to prevent such events in future. Methods: This prospective observational study was conducted in two tertiary hospitals of Maharashtra, from July 2018 to November 2020. All women during pregnancy, childbirth or postpartum upto 42 days meeting the eligibility criteria of MNM as per the 2014 GoI guidelines were included as cases (n=228), interviewed and discussed during the monthly MNM meetings at these hospitals. Results: The incidence of MNM was 11/1000 live births; the ratio of MNM to maternal deaths was 1.2:1. Leading causes of MNM were haemorrhage (36.4%) and hypertensive disorders of pregnancy (30.3%). Haemorrhage was maximum (70.6%) in abortion and ectopic pregnancies. Majority of the women (80.2%) were anaemic, of whom 32.4 per cent had severe anaemia. Eighty six per cent of women included in the study had MNM events at the time of admission and 81 per cent were referred from lower facilities. Level one and two delays were reported by 52.6 and 32.5 per cent of women, respectively. Level three delay at referral centres and at tertiary hospitals was reported by 69.7 and 48.2 per cent of women, respectively. Interpretation & conclusions: The findings of this study suggest that MNM-R should be undertaken at all tertiary hospitals in India as per GoI guidelines to identify gaps based on three-delay model. These hospitals should implement interventions as per the identified gaps with emphasis on strengthening the infrastructure, facilities and manpower at the first-referral units.

Assessment of Health-Related Quality of Life Using PCOSQ Tool, Its Determinants and Coping Mechanisms Used by Women with Polycystic Ovarian Syndrome Attending Multidisciplinary Clinic in Mumbai, India.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder having most impact on women of reproductive age group, affecting their quality of life (HRQOL) and psychological well-being. Objective: This paper aims to determine QOL among women affected with PCOS attending a multidisciplinary clinic using PCOSQ tool and its association with socio-economic status, phenotypes, anxiety, depression and metabolic comorbidities and evaluate the coping strategies adapted by these women. Design: Retrospective study. Setting: Integrated multidisciplinary PCOS clinic. Patients: Two hundred and nine women diagnosed with PCOS as per Rotterdam criteria. Results: Infertility was an important condition for reduced HRQOL and psychological morbidity across all socio-economic status and phenotypes. The poor psychological status and obesity were identified as determinants of HRQOL among women affected with PCOS. Those who suffered from anxiety, depression and showed lower HRQOL used emotional maladaptive coping strategies. Conclusion: Results reveal that HRQOL of PCOS women is worsened in the presence of comorbidities. Maladaptive and disengagement coping strategies used by women may worsen their psychological status. Holistic assessment of comorbidities and its management can help improve HROL of affected women. Personalised counselling based on the assessment of coping strategies used by women could empower women to cope better with PCOS.

Dysregulated serum and seminal plasma levels of surfactant protein D and MCP-1 in men with genital tract infection/inflammation.

PROBLEM: Surfactant protein D (SP-D), a multimeric collectin expressed by testicular mucosal epithelia and is positively regulated by testosterone. It exerts antimicrobial effects, modulates inflammation and rescued spermatogenesis in a murine model. Various cytokines and chemokines, including MCP-1, play a key role in regulating the inflammation in rat and human testis. The study aimed to investigate the role of SP-D and involvement of chemokines and cytokines in the male infertility associated with urogenital infections or inflammation. METHOD OF STUDY: The cross-sectional study evaluated levels of SP-D, testosterone, estradiol and the cytokines/chemokines including MCP-1 in the serum and semen samples of fertile and infertile Indian men with and without urogenital infections/inflammation (n = 76). RESULTS: Both fertile and infertile males with urogenital infection/inflammation had significantly lower levels of SP-D and higher levels of the chemokine, Monocyte chemoattractant protein 1 (MCP-1) in the serum and seminal plasma. Seminal plasma of these males exhibited significantly higher proportion of proteolytically degraded forms of SP-D. The serum SP-D levels positively correlated with testosterone/estradiol (TE) ratio. There was no significant correlation between the SP-D levels in seminal plasma and sperm count/motility. With a significant area under the Receiver Operating Characteristic curves, the serum and seminal plasma SP-D levels exhibited significant potential to predict infertility with high sensitivity and specificity in men with genital infections/inflammation. CONCLUSIONS: The circulating and seminal plasma SP-D levels were decreased in men with urogenital infection and inflammation. This could be due to their engagement at the site of infection, dysregulated expression owing to the altered hormonal profile and increased proteolytic degradation.

Whole genome bisulfite sequencing of sperm reveals differentially methylated regions in male partners of idiopathic recurrent pregnancy loss cases.

OBJECTIVE: To study the genome wide alterations in sperm DNA methylation in male partners of idiopathic recurrent pregnancy loss (iRPL) cases and note regions as potential diagnostic markers. DESIGN: Case-control study and methylome analysis of human sperm. SETTING: Obstetrics and Gynaecology clinics. PATIENT(S): Control group consists of apparently healthy fertile men having fathered a child within the last 2 years (n = 39); and case group consists of male partners of iRPL cases having ≥2 consecutive 1st trimester pregnancy losses (n = 47). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm DNA samples of controls and cases were selected for whole genome bisulfite sequencing analysis based on the previously set thresholds of global methylation levels and methylation levels of imprinted genes (KvDMR and ZAC). Whole genome bisulfite sequencing of selected sperm genomic DNA was performed to identify differentially methylated CpG sites of iRPL cases compared with fertile controls. Pathway analysis of all the differentially methylated genes was done by Database for Annotation, Visualization, and Integrated Discovery annotation tool and Kyoto Encyclopedia of Genes and Genomes tool. Differentially methylated CpGs within genes relevant to embryo and placenta development were selected to further validate their methylation levels in study population by pyrosequencing. RESULT(S): A total of 9497 differentially methylated CpGs with highest enrichment in intronic regions were obtained. In addition, 5352 differentially methylated regions and 2087 differentially methylated genes were noted. Signaling pathways involved in development were enriched on pathway analysis. Select CpGs within genes PPARG, KCNQ1, SETD2, and MAP3K4 showed distinct hypomethylated subpopulations within iRPL study population. CONCLUSION(S): Our study highlights the altered methylation landscape of iRPL sperm, and their possible implications in pathways of embryo and placental development. The CpG sites that are hypomethylated specifically in sperm of iRPL subpopulation can be further assessed as predictive biomarkers.

Molecular characterization of variants in mitochondrial DNA encoded genes using next generation sequencing analysis and mitochondrial dysfunction in women with PCOS.

Emerging studies indicates mitochondrial dysfunction and involvement of mitochondrial DNA (mtDNA) variants in the pathogenesis of polycystic ovary syndrome (PCOS). Cumulative effect of mtDNA rare variants are now gaining considerable interest apart from common variants in the pathogenesis of complex diseases. Rare variants may modify the effect of polymorphism or in combination with the common variants may affect the risk of disease. With the evolution of high throughput sequencing techniques, which can be utilized to identify common as well as rare variants along with heteroplasmy levels, comprehensive characterization of the mtDNA variants is possible. Till date, few studies reported common mtDNA variants using traditional sequencing techniques but rare variants in mtDNA encoding genes remain unexplored in women with PCOS. These mtDNA variants may be responsible for mitochondrial dysfunction and may contribute in PCOS pathogenesis. In this study we determined mtDNA copy number, a biomarker of mitochondrial dysfunction and first time analysed variants in mtDNA encoded genes in women with PCOS using mitochondrial Next Generation sequencing (NGS) approach and compared allele frequency from mitochondrial 1000 genome dataset. Variant annotation and prioritization was done using highly automated pipeline, MToolBox that excludes reads mapped from nuclear mitochondrial DNA sequences (NumtS) to identify unique mtDNA reads. The present study identified significant reduction in mtDNA copy number in women with PCOS compared to non-PCOS women. A total of unique 214 prioritized common to rare variants were identified in mtDNA encoded genes, 183 variants in OXPHOS complexes, 14 variants in MT-tRNA and 17 variants in MT-rRNA genes that may be involved in mitochondrial dysfunction in PCOS. Numerous variants were heteroplasmic, pathogenic in nature and occurred in evolutionary conserved region. Heteroplasmic variants were more frequently occurred in MT-CO3 gene. Non-synonymous variants were more than synonymous variants and mainly occurred in OXPHOS complex I and IV. Few variants were found to be associated with diseases in MITOMAP database. The study provides a better understanding towards pathogenesis of PCOS from novel aspects focusing on mitochondrial genetic defects as underlying cause for contributing mitochondrial dysfunction in women with PCOS.

Characterization of peripheral T helper 17 (Th17) cells phenotype in postmenopausal women with estrogen insufficiency.

Over the past few years, Th17 cells is considered a key player in osteoporosis pathogenesis. Although extensively studied in murine models, comprehensive Th17 cell characterization in osteoporotic women is elusive. We thus aimed to examine peripheral Th17 cells frequency and phenotypes in healthy and osteoporotic women. Our results demonstrated that Th17 cells were primarily CD4+CD45RA-CCR7-HALDR+CCR6lowT-cells. Compared to Pre-N, Post-L showed increased proportion of Th17 with concomitant decrease in Th1 cells. The Th17 cells frequency in effector memory CD4+ T cells was significantly elevated in Post-N with a decrease of Th1 cells in effector memory subsets compared to Pre-N and Post-L. Both Post-N and Post-L had decreased frequency of dual positive Th1-Th17 cells and increased HLA-DR expression on Th17 cells compared to Pre-N. Thus, our study demonstrates increased Th17 cells frequency and reduced Th1 cells frequency with effector memory phenotype in postmenopausal women with estrogen insufficiency and correlates with aging process.

Yoga Intervention Improves the Metabolic Parameters and Quality of Life among Infertile Women with Polycystic Ovary Syndrome in Indian Population.

Background: The heterogenic manifestations of polycystic ovarian syndrome have led to various treatment approaches that include improving hormonal imbalance, weight management, and improving quality of life (QoL). Yoga therapy being a versatile treatment approach benefits physical and mental well-being and can be recommended to women with polycystic ovary syndrome (PCOS). Objective: The objective of this study was to study the effect of structured yoga intervention on anthropometric, metabolic, hormonal, biochemical, ovarian morphology, and infertility-related QoL parameters among infertile women with PCOS. Settings and Design: A prospective, controlled before and after study was conducted at a Multidisciplinary PCOS Clinic in Mumbai, Maharashtra, India. Methodology: Infertile women with PCOS (26 participants in each group which includes intervention and control arm) seeking treatment for infertility at the Multidisciplinary PCOS Clinic at National Institute for Research in Reproductive and Child Health. The intervention group received 90 min of structured yoga intervention for 3 months. Statistical Analysis: The median change in parameters between baseline and after 12 weeks of intervention was analyzed using IBM SPSS software, version 26 to perform descriptive analyses and Wilcoxon test to analyze pre- and postintervention parameters in the intervention and control group. Results: There was a significant difference in the weight, basal metabolic rate, postglucose insulin, anti-Müllerian hormone, cholesterol, high-density lipoprotein, low-density lipoprotein, serum glutamic pyruvic transaminase, ultrasound parameters such as stromal thickness, follicle number per ovary, and QoL in infertility domain in the intervention group compared to the control group. Within 1 year of initiation of the study, 13 participants became pregnant in the yoga intervention group as compared to 7 participants in the control group. Conclusion: The metabolic comorbidities of PCOS have adverse effects on the QoL and pregnancy outcome among infertile women with PCOS. This pilot study demonstrated that a 12-week yoga intervention brought overall improvement in anthropometric, hormonal, biochemical, ovarian morphology, and infertility-related QoL parameters compared to the control group. Integration of yoga in infertility management will help to improve the QoL and to optimize prepregnancy metabolic parameters among infertile women with PCOS.

Evaluation of cytokine profile in cervicovaginal lavage specimens of women having asymptomatic reproductive tract infections.

Reproductive tract infections (RTIs) such as vaginal candidiasis and bacterial vaginosis (BV) are common among sexually active women and can be both symptomatic or asymptomatic. The microbiota of the reproductive tract triggers immune response at the cervicovaginal interface resulting in secretion of cytokines during the course of these RTIs. The objective of this study was to evaluate the cytokine profile in cervicovaginal lavage of women having asymptomatic vaginal infections. Measurement of vaginal cytokines was done for various interleukins including IL-1ß, IL-6, IL-8, IL-10, IL-12/IL23p40, IL-17A, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) by ProcartaPlex™ Multiplex Immunoassay. Women having vaginal Candida infection had increased concentration of IL-1ß (p=.01), IL-6 (p=.007), IL-8 (p=.327), IL-12/IL23p40 (p=.049) and IFN-γ (p=.125). The results of our study suggest that evaluation of these cytokines could be explored as an additional measure to determine host inflammatory response in women having asymptomatic vaginal candidiasis.Impact StatementWhat is already known on this subject? Studies assessing the vaginal cytokine profile to assess the vaginal milieu in various cohorts such as post-menopausal women, pregnant women, women with history of preterm birth, CIN and scheduled IVF cycle are being undertaken. Variable cytokine response has been reported in literature in women with symptomatic bacterial vaginosis and Candida infection. However, much less is known about vaginal cytokine profile in asymptomatic infection.What do the results of this study add? The results of the study show increased concentration of the pro-inflammatory cytokines IL-1ß, IL-6 IL-8, IL-12/IL23p40 and interferon gamma (IFN-γ) in women having asymptomatic Candida, vaginal leucocytosis and raised vaginal pH.What are the implications of these findings for clinical practice and/or further research? Evaluation of vaginal cytokine profile (IL-1ß, IL-6 IL-8, IL-1ß, IL-12/IL23p40 and IFN-γ) could be explored as an additional measure to determine inflammation in asymptomatic women. Vaginal cytokines (IL-1ß, IL-6 IL-8, IL-1ß, IL-12/IL23p40 and IFN-γ) could be used further for development of a point of care test.

Association of OPG and RANKL gene polymorphisms with bone mineral density in Indian women.

Osteoprotegerin (OPG) and receptor activator of the NF-kB ligand (RANKL) are key players in bone remodelling. Reports show that OPG and RANKL gene polymorphisms are associated with osteoporosis and fracture risk. The aim of this study was to examine the influence of 5 single nucleotide polymorphisms (SNPs) in OPG and RANKL gene on bone mineral density (BMD) in Indian women. The study included 374 healthy Indian women. Kompetitive Allele Specific PCR (KASP) was used for genotyping. There was a significant difference in the BMD at spine between genotypes of OPG rs2073618 (CC: 0.988 ± 0.167 CG: 1.023 ± 0.17 GG: 1.053 ± 0.155; p = 0.039) which was lost upon adjustment for age and BMI (p = 0.087). Multiple linear regression revealed that genotypes of OPG rs2073618 (ß = 0.098; p = 0.027) and rs3102735 (ß = 0.092; p = 0.038) are predictors of BMD at spine in Indian women. We did not observe any association of SNPs in RANKL gene with BMD. Thus, SNPs rs2073618 and rs3102735 in OPG gene may influence BMD at spine in Indian women.

Cross sectional study to evaluate microbiological spectrum of RTI/STI and co-infections among women with cervicitis or cervico-vaginitis from a community clinic in Mumbai.

Cervicitis is an inflammatory condition of cervix, when presented along with vaginal discharge; it is termed as cervico-vaginitis. These can be infective, hence important to diagnose due to risk of spreading to upper genital tract. This cross-sectional study was undertaken to evaluate the microbiological spectrum in cervicitis or cervico-vaginitis among 100 sexually active women by Gram stain and Multiplex Real time polymerase chain reaction. Bacterial vaginosis 21(21%) was the most common RTI. Among STIs, genital mycoplasmas were the predominant infections hence further research is required to understand their pathogenesis.

An integrated multidisciplinary model of care for addressing comorbidities beyond reproductive health among women with polycystic ovary syndrome in India.

Background & objectives: Polycystic Ovary Syndrome (PCOS) is becoming an area of global and national health concern. It requires a life cycle approach from adolescence to menopause. To comprehensively address the wide spectrum of this disorder, a multidisciplinary model of care was established for women with PCOS in a government setting in India with an objective to screen and manage multifaceted manifestations of PCOS and to diagnose and treat associated comorbidities such as metabolic syndrome, dermatologic manifestations and psychological issues. Methods: A model of integrated multidisciplinary PCOS clinic was implemented for services and research at ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai Maharashtra, India. This is a one-stop holistic centre for managing menstrual, cosmetic, infertility, obesity, metabolic and psychological concerns of women affected with PCOS. Two hundred and twenty six women diagnosed with PCOS using the Rotterdam criteria were screened for metabolic comorbidities with anthropometry, ultrasonography, hormonal and biochemical tests and for psychological problems. Analysis was performed using SPSS version 19.0. Results: Mean body mass index (BMI) was 26.1 kg/m2, higher for Asians. Hirsutism was observed in 53.6 per cent of women. Metabolic syndrome was seen among 35.3 per cent and non-alcoholic fatty liver in 18.3 per cent. Psychological issues such as anxiety and depression were identified in majority of the women 31.4 per cent of women could achieve pregnancy at the end of one year of multidisciplinary management. Interpretation & conclusions: The results of the present study suggest that an integrated multidisciplinary approach led to the early identification and treatment of comorbidities of PCOS, especially metabolic syndrome. There is hence an urgent need to implement multidisciplinary PCOS clinics in government health facilities.

Enablers & challenges of tribal women & health system for implementation of screening of non-communicable diseases & common cancers: A mixed-methods study in Palghar district of Maharashtra, India.

Background & objectives: Non-communicable diseases (NCDs) and cancers of breast, oral cavity and cervix contribute to around 5.87 million (60%) deaths in India. Despite this, there is limited evidence on preparedness of the tribal health system in mitigating these conditions. This mixed-methods study aimed at identifying enablers and challenges using a multistakeholder approach for the screening of NCDs and common cancers in a tribal block of Maharashtra, India. Methods: This study was conducted in a tribal community of Dahanu taluka in Palghar district of Maharashtra. A total of nine focus group discussions (FGDs) among tribal women and accredited social health activists (ASHAs), 13 key informant interviews (KIIs) among auxiliary nurse midwives (ANMs) and community health officers (CHO) and facility surveys of five public health facilities were conducted. The FGDs and KIIs were conducted using guides, recorded digitally, transcribed, analyzed and triangulated to identify emerging themes. Results: The tribal women had limited knowledge about NCDs and common cancers. Paucity of health facilities, out-of-pocket expenditure, misconceptions, belief on traditional healers and inability to prioritize health were identified as major challenges. The ASHAs were recognized as a key connecting link between health system and community while provision of culturally appropriate IEC materials and adequate training were recognized as critical enablers by healthcare providers in implementing screening for NCDs and common cancers. Interpretation & conclusions: The study recommends incorporating socioculturally relevant strategies in the tribal population and strengthening health facilities in terms of infrastructure and training with involvement of ASHAs for successful implementation of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) through health and wellness centres.