Relation of mitochondrial DNA copy number and variants with the clinical characteristics of polycystic ovary syndrome.

Mounting evidences suggests mitochondrial dysfunction as a novel contributor in the pathogenesis of PCOS. Herein, we analyzed mtDNA copy number, a biomarker of mitochondrial function in women with PCOS and non-PCOS participants and study its correlation with their clinical characteristics. In this study, we further analyzed association of 383 mtDNA variants, as reported previously by us, with characteristic traits of PCOS and perform structural analysis of mutated protein. Our results indicate relative mitochondrial DNA (mtDNA) copy number to be significantly reduced in women with PCOS compared to non-PCOS group and significantly inversely related to waist to hip ratio (WHR), triglycerides and positively related to high density lipoprotein-cholesterol (HDL-C). After adjustment of the age in the PCOS group, significantly negative correlation of mtDNA copy number with WHR was observed. Unsupervised hierarchical clustering analysis revealed rare, low heteroplasmic mtDNA variants such as 12556G, 1488T, 9200G, 9670G, 3308G, 14480G, 15914T and 5426G to be strongly associated with PCOS related traits. Among these variants, variant 12256G in ND5 gene affected both the flexibility and overall stability of the protein structure. This study is first to reveal significant correlation of mtDNA copy number with WHR in women with PCOS indicating link between mitochondrial dysfunction with central obesity in PCOS. we also first time showed association of rare mtDNA variants with characteristics traits of PCOS highlighting the clinical significance of rare mtDNA variants, which may cumulatively act as early predictors of risk of PCOS and its related comorbidities which may help in the management of PCOS.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Common Hematological Reference Indices Among Healthy Reproductive Age Indian Women-Data Subset from Nationwide Study.

Despite the negative implications on women's health, pregnancy, and fetal outcomes, population-based studies on hematological indices among reproductive age women in India have received inadequate attention. This study aimed to generate normative ranges for various hematological parameters among these women. After ethics approval, apparently healthy (n = 5884) women (aged 18-40 years) were recruited from six eco-geographic zones of India. After various exclusions (n = 5412), including women having anemia, data of clinically, and biochemically healthy women (n = 472) was analysed to generate centiles (2.5 and 97.5th) and correlations. The mean age and mean BMI of women was 29.3 ± 6.5 years and 23.25 ± 3.26 kg/m2 with BP of 112.26 ± 8.9/74.04 ± 6.7 mmHg. The reference intervals for hemoglobin (12-15.1 gm/dl), RBC (3.68-5.55 millions/µl), WBC (4.1-11.26*109/L), platelet count (1.32-4.42*105/µl), and erythrocyte sedimentation rate (4.35-41.65 mm/hr) were different from currently used reference values (p < 0.05). However, these haematological indices did not vary among various age categories, geographical zones, ethnicities and rural or urban origins. Pearson's correlation revealed a statistically significant association between ESR, WBC, monocytes, and platelets with homeostasis model assessment of insulin resistance (HOMA-IR). Women with HOMA-IR > 2 displayed a statistically significant differences in parameters like MCV, ESR, eosinophil and platelet counts as compared to the women with HOMA-IR < 2. This study provides a pioneering reference data of hematological indices among women of reproductive age in India. Despite the small sample size results can be extrapolated to the national population given the representative sampling of various geographical zones. This may pave way for future comprehensive large-scale studies on the subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01714-6.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

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.

Health facility-based interventions and the uptake of contraception among people living with HIV: A systematic review & meta-analysis.

BACKGROUND OBJECTIVES: The prong 2 of 4 prong strategy introduced by the World Health Organization aims at averting unintended pregnancies among people living with HIV (PLHIV). This systematic review aimed to generate evidence on the effectuality of facility-based interventions in improving uptake of modern and dual contraception, for reducing unmet family planning (FP) needs and unintended pregnancies among PLHIV. METHODS: Articles evaluating facility-based interventions to integrate human immunodeficiency virus (HIV) and FP published in English language were included. Eligible studies were identified from electronic and lateral search from three databases (PubMed, Cochrane Library and Web of Science) and grey literature. HIV care with no/minimal focus on FP was considered a comparator. Quality was assessed using design-appropriate tools. Descriptive analysis was presented in tables. Uptake of dual methods, unmet FP needs and unintended pregnancies were included in the meta-analysis to estimate pooled odds ratio (OR) with random effect model, P and I2 values. RESULTS: The search yielded 2112 results. After excluding duplicates and unfit articles, 17 were found eligible for review and nine for meta-analysis. The pooled OR for uptake of dual contraception was 1.69 (1.14, 2.5) ( P =0.008; I2 =90%), for unmet FP needs was 0.58 (0487, 0.69) ( P <0.00001; I2 =0%) and for unintended pregnancies was 0.6 (0.32, 1.1) ( P =0.1, I2 =38%). INTERPRETATION CONCLUSIONS: The results of this meta-analysis suggest that health facility-based interventions to integrate HIV and FP services do result in improved uptake of dual methods and reduce unmet need for contraception along with a protective trend on incidence of unintended pregnancies. Such facility-based integration would ensure universal access to effective contraception and facilitate in achieving Sustainable Development Goals that aim at ending epidemics like HIV.

Health system cost for providing antiretroviral therapy, family planning, and pregnancy-related services to women living with HIV in public health settings, Mumbai, India.

Background: Integration of HIV care into family planning (FP) services would help in reducing unintended pregnancies among women living with HIV. Objectives: This study focuses on determining the health system cost for providing the linked HIV-FP services per beneficiary for the year 2019-2020. Materials and Methods: Using mixed micro-costing approach costs were collected from two tertiary hospitals in Maharashtra, India. The economic costs collected from gynaecology department and anti-retroviral treatment center were combined and added with package, program, and intervention costs to obtain health-system costs. We conducted probabilistic sensitivity analysis. Results: The unit cost and annual per-capita cost for providing HIV care (without considering cost of drugs and investigations) per beneficiary were INR 1033.8 (USD 13.6) and INR 9304.2 (USD 122.7), respectively. The unit cost was least for the outpatient services INR 197.5 (USD 2.6), followed by inpatient services INR 2735.92 (USD 36.21) and operation theater INR 4410 (USD 58.2). Cost was highest for dual-permanent (INR 13866.8 [USD 182.9]) followed by dual-reversible user (INR 2104.8 [USD 24.8]). It was the least for a person who only used condoms at INR 1674.1 (USD 22.1). In pregnancy-related services, cost for ante-natal services was least (INR 2043.6 [USD 27.96]), followed by vaginal delivery (INR 7120.5 [USD 93.93]), abortion (INR 11530.5 [USD 152.097]), and C-section (INR 18703.8 [USD 246.7]). Conclusion: We found no staggeringly additional costs for providing FP and pregnancy-related services to HIV-affected population, in comparison to general population. The findings could improve programs and insurance with a focus on this vulnerable population.

Prevalence, Regional Variations, and Predictors of Overweight, Obesity, and Hypertension Among Healthy Reproductive-Age Indian Women: Nationwide Cross-Sectional Polycystic Ovary Syndrome Task Force Study.

BACKGROUND: A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease prevention, particularly in India. There is a paucity of nationally representative data on the dynamics of these risk factors, which have not been assessed among healthy reproductive-age Indian women. OBJECTIVE: This cross-sectional polycystic ovary syndrome (PCOS) task force study aimed to assess the anthropometric and sociodemographic characteristics of healthy reproductive-age Indian women and explore the association of these characteristics with various noncommunicable diseases. METHODS: We conducted a nationwide cross-sectional survey from 2018 to 2022 as part of the Indian Council of Medical Research-PCOS National Task Force study, with the primary aim of estimating the national prevalence of PCOS and regional phenotypic variations among women with PCOS. A multistage random sampling technique was adopted, and 7107 healthy women (aged 18-40 years) from 6 representative geographical zones of India were included in the study. The anthropometric indices and sociodemographic characteristics of these women were analyzed. Statistical analysis was performed to assess the association between exposure and outcome variables. RESULTS: Of the 7107 study participants, 3585 (50.44%) were from rural areas and 3522 (49.56%) were from urban areas. The prevalence of obesity increased from 8.1% using World Health Organization criteria to 40% using the revised consensus guidelines for Asian Indian populations. Women from urban areas showed higher proportions of overweight (524/1908, 27.46%), obesity (775/1908, 40.62%), and prehypertension (1008/1908, 52.83%) categories. A rising trend of obesity was observed with an increase in age. Women aged 18 to 23 years were healthy (314/724, 43.4%) and overweight (140/724, 19.3%) compared with women aged 36 to 40 years with obesity (448/911, 49.2%) and overweight (216/911, 23.7%). The proportion of obesity was high among South Indian women, with 49.53% (531/1072) and 66.14% (709/1072), using both World Health Organization criteria and the revised Indian guidelines for BMI, respectively. BMI with waist circumference and waist-to-height ratio had a statistically significant linear relationship (r=0.417; P<.001 and r=0.422; P<.001, respectively). However, the magnitude, or strength, of the association was relatively weak (0.3<|r|<0.5). Statistical analysis showed that the strongest predictors of being overweight or obese were older age, level of education, wealth quintile, and area of residence. CONCLUSIONS: Anthropometric and sociodemographic characteristics are useful predictors of overweight- and obesity-related syndromes, including prehypertension, among healthy Indian women. Increased attention to the health of Indian women from public health experts and policy makers is warranted. The findings of this study can be leveraged to offer valuable insights, informing health decision-making and targeted interventions that mitigate risk factors of overweight, obesity, and hypertension. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23437.

Normative range of various serum hormonal parameters among Indian women of reproductive age: ICMR-PCOS task force study outcome.

Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th-97.5th centile) observed were: serum T4: µg/dL (5.23-12.31), TSH: µg/mL (0.52-4.16) and serum prolactin: ng/mL (5.13-37.35), LH: mIU/mL (2.75-20.68), FSH: mIU/mL 2.59-15.12), serum total testosterone: ng/mL (0.06-0.68), fasting insulin: mIU/mL (1.92-39.72), morning cortisol: µg/dL (4.71-19.64), DHEAS:µg/dL (50.61-342.6) and SHBG: nmol/L (21.37-117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p < 0.05). The comparative analysis showed marginal differences in the normative ranges for the hormones analysed among different populations. Interpretation: Our first large composite data on hormonal measures will benefit future endeavours to define biological reference intervals in reproductive-aged Indian women. Funding: The study was financially supported by the grant-in-aid from ICMR vide file No:5/7/13337/2015-RBMH.

Assessment of Health-Related Quality of Life Using EQ-5D-5L Tool With Indian Tariffs Among Reproductive Age Group Women Living With HIV in India.

OBJECTIVE: India is witnessing declining HIV prevalence because of dedicated efforts by the government. The highly active antiretroviral therapy has improved life span of people living with HIV but bearing many side effects. Women living with HIV (WLHIV) in reproductive age group have additional burden of pregnancy-related issues. This study aimed to estimate the health utility score among WLHIV in India, particularly in context of their contraceptive use, during pregnancy and postpartum period. METHODS: A primary cross-sectional study was conducted among 195 WLHIV availing antiretroviral treatment services at public health facilities of Mumbai. The EQ-5D-5L interview-based questionnaire in local language and Indian value set was used to estimate health-related quality of life (QOL) reported as mean (± SD) utility and visual analog scale (VAS) scores. The relationship between utility values and VAS scores was assessed. RESULTS: The WLHIV with mean age of 31.6 (6.4) years were on antiretroviral medication for nearly 7 years, and 63% had CD4+ cell count > 500 cells/mm3. Response of "11111," that is, in full health state, was reported by 66.7%. The mean utility and VAS scores were 0.976 (± 0.0519) and 82.21 (± 15.77). Reduced health-related QOL scores were associated with pain and discomfort dimension. Utility scores among contraceptive users (0.986 [± 0.029]) was higher than nonusers (0.976 [± 0.028]). Currently pregnant WLHIV had least utility score (0.959 [± 0.088]). CONCLUSIONS: WLHIV had better QOL while using contraceptives more so when they were sterilized. Pregnancy reduces the QOL. This emphasizes the need to promote effective contraceptive methods among WLHIV and prevent unintended pregnancies.

Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India: A subset of data from a National Indian Council of Medical Research-Polycystic Ovary Syndrome task force study.

OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A.total of 13,181 women of reproductive age (18-40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th-97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.

Addressing Challenges During Community based Screening of Women for Polycystic Ovary Syndrome (PCOS): A Research Experience from Maharashtra, India before and During COVID Pandemic.

Introduction: A multicentric community-based screening to determine prevalence of Polycystic Ovary Syndrome was undertaken in India. This article aims to describe the challenges faced at one site and strategies adopted to mitigate them. Material and Methods: Eligible women were enrolled at household-level and investigated for Polycystic Ovary Syndrome diagnosis as per Rotterdam criteria. Challenges faced were documented and alternate strategies were adopted. Results: Challenges ranged from identifying women as per the polling booth list, enrolling them, and getting them investigated. COVID-19 pandemic added to the challenges. Involving health system workforce, gaining community support, flexible timings, and alternate strategies for investigation including COVID-19 appropriate safety measures helped mitigate some of the challenges. Conclusion: Unforeseen challenges may crop up in community-based studies, like the ones faced during the COVID-19 pandemic. Planning, strategizing, using technology to keep communications on, and finding out of the box and amicable solutions for bottlenecks may help mitigate challenges.

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.

Determining the Impact of the COVID-19 Pandemic on Availability, Use, and Readiness of Family Planning and Contraceptive Services at Selected Primary Health Care Facilities in Africa and Asia: Protocol for a Mixed Methods Study.

BACKGROUND: The COVID-19 pandemic and the associated social restrictions may have disrupted the provision of essential services, including family planning (FP) and contraceptive services. This protocol is adapted from a generic study protocol titled "Health systems analysis and evaluations of the barriers to availability and readiness of sexual and reproductive health services in COVID-19 affected areas," conducted by the World Health Organization (WHO) Department of Reproductive Health and Research. OBJECTIVE: This study aims to assess the availability and use of FP and contraceptive services in primary health facilities during and after the COVID-19 pandemic; assess the risk perceptions of COVID-19 stigma, barriers to access, and quality of services from clients' and providers' perspectives in the COVID-19-affected areas; and assess the postpandemic recovery of the facilities in the provision of FP and contraceptive services. METHODS: In-depth interviews will be conducted with clients-women in the reproductive age group and their male partners who visit the selected health facilities for FP and contraceptive services-and health providers (the most knowledgeable person on FP and contraceptive service provision) at the selected health facilities. Focus group discussions will be conducted with clients at the selected health facilities and in the community. The in-depth interviews and focus group discussions will help to understand clients' and health service providers' perspectives of FP and contraceptive service availability and readiness in COVID-19-affected areas. A cross-sectional health facility assessment will be conducted in all the selected health facilities to determine the health facility infrastructure's ability and readiness to provide FP and contraceptive services and to capture the trends in FP and contraceptive services available during the COVID-19 pandemic. Scientific approval for this study is obtained from the WHO Research Project Review Panel, and the WHO Ethics Review Committee has given ethical approval in the 3 countries. RESULTS: Using a standardized research protocol will ensure that the results from this study can be compared across regions and countries. The study was funded in March 2021. It received ethics approval from the WHO Ethics Review Committee in February 2022. We completed data collection in September 2022. We plan to complete the data analysis by March 2023. We plan to publish the study results by Summer 2023. CONCLUSIONS: The findings from this study will provide a better understanding of the impact of the COVID-19 pandemic on FP and contraceptive services at the facility level, which will help policy makers and health managers develop and strengthen FP policies and services in health facilities to be more responsive to community needs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43329.

Cost-effectiveness and budget impact of adding tranexamic acid for management of post-partum hemorrhage in the Indian public health system.

BACKGROUND: Postpartum hemorrhage (PPH) is the global leading cause of maternal mortality, affecting nearly 3 to 6 percent of all women giving birth in India. The World Health Organization (WHO) has updated its guidelines to recommend the early use of intravenous (IV) tranexamic acid (TXA) in addition to standard care for all diagnosed PPH cases. This study aimed to assess the cost-effectiveness of introducing TXA for PPH management in the Indian public health system. METHODS: A decision analytic model was built using a decision tree to determine the cost-effectiveness of administering IV TXA to women experiencing PPH within 3 h of birth to existing management with uterotonics and supportive care. Using a disaggregated societal perspective, the costs and consequences for a hypothetical cohort of women experiencing PPH in public health facilities was estimated. The model was populated using probabilities, clinical parameters, and utilities from published literature, while cost parameters were largely derived from a primary economic costing study. The primary outcome of interest was the incremental cost-utility ratio (ICUR). Associated clinical events and net benefits were estimated. One-way and probabilistic sensitivity analysis (PSA) was undertaken. The budget impact was estimated for a national-level introduction. RESULTS: For an estimated annual cohort of 510,915 PPH cases in India, the addition of IV TXA would result in a per-patient disaggregated societal cost of INR 6607 (USD 95.15) with a discounted gain of 20.25 QALYs, as compared to a cost of INR 6486 (USD 93.41) with a discounted gain of 20.17 QALYs with standard care PPH management. At an ICUR value of INR 1470 per QALY gained (USD 21), the addition of IV TXA is cost-effective in Indian public health settings. The intervention is likely to prevent 389 maternal deaths, 177 surgeries, and 128 ICU admissions per 100,000 PPH cases. The findings are robust under uncertainty, with 94.5% of PSA simulations remaining cost-effective. A cumulative increase of 2.3% financial allocation for PPH management over five years will be incurred for TXA introduction. CONCLUSIONS: Addition of tranexamic acid for primary PPH management, as recommended by WHO, is cost-effective in Indian public health settings. Policy guidelines, training manuals, and facility checklists should be updated to reflect this recommendation.

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.

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.

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.

Cost of providing family planning services & management of pregnancy outcomes at public health facilities in India.

Background & objectives: Lack of costing data is a critical gap that exists in the field of family planning (FP) in India. The aim of this study was to estimate health system costs of FP in India for existing modern methods, and potential newer methods (etonorgestrel implant and levonorgestrel intrauterine device) and pregnancy-related services in India. Methods: A bottom-up micro-costing study was conducted in five public health facilities of an Indian State. Data of last one year were collected from existing hospital records and hospital staff was interviewed. Collected data were analyzed using standard costing methods. Results: Package costs of delivering FP services ranged from ₹ 807 (95% CI 685, 931) for condoms and ₹ 10,539 (8796, 12269) for tubal ligation. Estimates of etonorgestrel implant and levonorgestrel intrauterine system were ₹ 3,200 (2800, 3625) and 3,426 (3232, 3623). Cost of antenatal care along with vaginal delivery, caesarean and abortion were ₹ 10,916 (8744, 13078), 22,136 (17570, 26910) and 8,574 (6791, 10379), respectively. One way sensitivity analysis showed that the three most influential factors on the costs of FP services were prices of drugs and consumables, number of beneficiaries and health personnel cost. Interpretation & conclusions: The present study has generated package costs for FP and pregnancy-related services in India which could be used by publicly-funded insurance schemes, for budgeting, economic evaluations and improve resource allocation of services. The cost estimates from this study add to the limited literature in India on costs of FP.