Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study.

The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

Evaluation of cervical cancer screening during pregnancy in India: Human papillomavirus testing can change the paradigm.

Background The World Health Organization's call for elimination of cervical cancer envisages 70% screening coverage of women aged 35 and 45 years by an effective test. In India, this target seems unrealistic as awareness and access to cancer prevention services are poor. However, the institutional delivery rate is now >80%. We evaluated the acceptability and feasibility of human papillomavirus (HPV) testing and its role in screening during pregnancy. Methods This observational study recruited 275 pregnant women aged >25 years between 12 and 34 weeks of gestation for screening by cytology and HPV testing. Colposcopy was advised if either test was positive. Acceptability and feasibility were assessed by a questionnaire. Results Cytology and HPV reports were available for 269 subjects. The median age was 28 years and median parity was two. Only 98 (36.4%) had heard about carcinoma cervix. Awareness improved with education (p < 0.001). On cytology, only 4 (1.5%) were abnormal (atypical squamous cells of undetermined significance 3; low-grade squamous intraepithelial lesion 1). The prevalence of high-risk HPV infection was 8.2% (22/269). On colposcopy, all had the Swede score <5. No high-grade cervical intraepithelial neoplasia or carcinoma was detected. Pre-procedure, 183 (68.0%) subjects expressed apprehension, post-procedure 114 (42.4%) of them had realized that their apprehensions were unfounded. Women found screening to be more uncomfortable after 28 weeks of gestation (n=26/68; 38.2%; p<0.001). Physicians found the cervix more difficult to visualize after 20 weeks of gestation (p<0.001). Conclusions HPV screening at 16-20 weeks of pregnancy is acceptable, feasible, and can greatly improve screening coverage in resource-limited settings. Pregnancy is a good opportunity to improve awareness of the screening programmes.

Primary leiomyosarcoma of the vulva - a rare occurrence.

Vulval tumours are rare, representing merely 4% of all gynaecological neoplasms. 98% of vulvar lesions are benign, and only 2% are malignant. Of all vulvar malignancies, while squamous cell carcinoma is the most common malignancy, leiomyosarcomas of the vulva are extremely rare. Usually these tumours have nonspecific clinical manifestations, often leading to misdiagnoses of Bartholin cysts or abscesses. We describe a case of a 47-year-old woman who presented with a nonspecific painless swelling in the left vulva for 2 months which was diagnosed as leiomyosarcoma of the vulva on biopsy as well as resection.

Implementation research to accelerate scale-up of national screen and treat strategies towards the elimination of cervical cancer.

BACKGROUND: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. MAIN BODY: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. CONCLUSION: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.

Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.

BACKGROUND: A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. METHODS: In the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. FINDINGS: Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2-9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0-99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3-99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5-99·7) in three-dose recipients (1460 women assessed). INTERPRETATION: A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. FUNDING: Bill & Melinda Gates Foundation.

The World Ovarian Cancer Coalition Every Woman Study: identifying challenges and opportunities to improve survival and quality of life.

INTRODUCTION: With the global incidence of ovarian cancer set to rise by 55% to 371 000 per year by 2035, current 5-year survival rates below 50%, and 15% of women with ovarian cancer dying within 2 months of diagnosis, urgent action is required to improve survival and quality of life. OBJECTIVE: To deal with the evidence gap relating to the experience of women with the disease around the globe and identify opportunities to drive progress. METHODS: The study included a review of global trends in incidence, mortality, and survival (October 2017); qualitative interviews with women and clinicians in 16 countries (December 2017); and an online survey for women available in 15 different languages (open for 2 months, March to early May 2018). Women were eligible to participate if they had been diagnosed in the previous 5 years and were proficient in one of the 15 languages offered. RESULTS: A total of 1531 women from 44 countries took part in the analysis. On average, 69.1% of women were not aware of ovarian cancer before their own diagnosis, varying from 50.9% (Hungary) to 86.4% (Brazil). A total of 78.3% of symptomatic women sought medical help, varying from 62.8% (Japan) to 87.7% (UK). Fewer than half of the women visited a doctor within 1 month (46.3%) of experiencing symptoms, varying from 38.5% (USA) to 77.3% (Germany), and a quarter of women waited 3 months or more. On average, 43.2% of women were diagnosed within 1 month of visiting a doctor, ranging from 30% (UK) to 62.3% (Italy). The average estimated time from experiencing symptoms to diagnosis was 31 weeks, but this ranged from 21.3 (Germany) to 39.7 (Brazil). Rates of post-diagnosis genetic testing ranged from 5.0% (Japan) to 79.1% (USA). Clinicians indicated that access to specialist treatment in high-volume centers varies greatly by country and region. CONCLUSION: The findings of this study identify some of the major challenges and opportunities to improve the time to diagnosis and management of women with ovarian cancer. These problems vary widely by country, and reducing the variability is an important first step towards improving outcomes for women with ovarian cancer.

Implications of the revised cervical cancer FIGO staging system.

The 2018 revised International Federation of Gynaecology and Obstetrics (FIGO) staging of cervical cancer has brought about a paradigm shift by offering the option of adding imaging and pathology to clinical staging. This makes it applicable to all types of resource situations across geographies with implications for all stakeholders, including gynaecologists, gynaecologic oncologists, radiologists, pathologists and radiation and medical oncologists. The new staging classification has more granularity, with three sub-stages of stage IB and a new category of stage IIIC for all cases with lymph node (LN) involvement. The major limitations of clinical staging were inaccurate assessment of tumour size and inability to assess pelvic and para-aortic LNs with the limited investigations permitted by FIGO to change the stage. This resulted in understaging of stages IB-III, and overstaging of stage IIIB, which has been largely overcome by incorporating imaging findings. Although any imaging modality can be used, magnetic resonance imaging appears to be the best imaging modality for early-stage disease owing to its better soft-tissue resolution. However, the use of contrast-enhanced computed tomography or ultrasonography are also feasible options, depending on the availability and resources. But wherever pathological evaluation is possible, it supersedes clinical and radiological findings.

Radiological evaluation of metastatic lymph nodes in carcinoma cervix with emphasis on their infiltrative pattern.

Background & objectives: Imaging has been added to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system of cervical carcinoma. This study was performed to assess the impact of imaging in staging and to ascertain the prevalence and pattern of nodal metastasis on contrast-enhanced computed tomography (CECT) in patients with cervical carcinoma who were treated based on FIGO 2009 staging system. Methods: This retrospective study was conducted to evaluate all patients with biopsy-proven cervical carcinoma who underwent CECT of abdomen at a tertiary cancer centre in north India from April 2017 to April 2019 and for whom either baseline or follow up scans were available. In patients with enlarged or necrotic lymph nodes, the location, size and pattern of infiltration of adjacent organs were recorded. Results: A total of 602 patients of cervical carcinoma had undergone CT during the study period, of whom 138 (22.9%) underwent CT at baseline and 464 (77.1%) patients during follow up. The FIGO (2009) stage distribution at the time of presentation was stage IB: 109 (18.1%); stage IIA: 14 (2.3%), stage IIB: 118 (19.6%), stage IIIA: 12 (2%), stage IIIB: 277 (46%), stage IVA: 20 (3.3%) and stage IVB: 52 (8.6%). Ninety of the 138 (65.22%) patients underwent a stage shift according to the FIGO 2018 because of the presence of enlarged lymph nodes at baseline scan. Sixteen (2.7%) patients had infiltrative nodal masses most commonly involving the blood vessels (n=14) followed by ureter (n=8), bones (n=5), muscle and bowel (n=3, each). The majority (14/16) of these patients presented with vague abdominal pain, discomfort and vomiting, while two had bone pain. Interpretation & conclusions: CECT at baseline helps in accurately assessing the stage in cervical carcinoma. It helps in the identification of lymph node metastasis in cervical carcinoma, which is crucial for guiding accurate management.

Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.

PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Predictors of chemotherapy resistance & relapse in gestational trophoblastic neoplasia.

BACKGROUND & OBJECTIVES: Gestational trophoblastic neoplasia (GTN) is a chemosensitive malignancy with an excellent cure rate. The primary objective of the present study was to determine the predictors of chemoresistance and disease relapse, and the secondary objective was to appraise the WHO/FIGO risk scoring and course of disease in women with GTN. METHODS: In this retrospective study, case records of women treated for GTN from January 2011 to June 2019 were reviewed. For the purpose of comparison, sub-stratification of FIGO/WHO low risk group (≤6) into low (0-4) and intermediate (5-6) risk was done. Similarly, WHO high risk (≥7) group was sub-stratified into high (7-12) and ultra-high risk (≥13) groups. RESULTS: Case records of 116 patients were included: 51.7 per cent (60/116) were of low risk disease and 48.2 per cent (56/116) were of high risk disease. Chemoresistance developed in 28.4 per cent (33/116) and relapse in 10.3 per cent (12/116) cases. Risk of chemoresistance was higher in low risk (0-6) while risk of relapse was more in high risk (≥7) group. On sub-stratification, chemoresistance was more with intermediate [0-4: 28.5% (10/35), 5-6: 44% (11/25), 7-12: 22.5% (9/40), ≥13: 18.7% (3/16)] and relapse with ultra-high risk score [0-4: 5.7% (2/35), 5-6: 4% (1/25), 7-12:10% (4/40), ≥13: 31.2% (5/16)]. Age, myometrial invasion, serum beta-human chorionic gonadotropin and tumour size were not related to chemoresistance or relapse. INTERPRETATION & CONCLUSIONS: WHO risk score and presence of metastatic disease predict the probability of developing chemotherapy resistance and disease relapse. Risk of chemotherapy resistance was higher in women with intermediate-risk score (5-6), and risk of relapse was more in those with ultra-high risk score (≥13).

Human papillomavirus vaccination: Good clinical practice recommendations from the Federation of Obstetric and Gynecological Societies of India.

Human papillomavirus (HPV) vaccination offers an excellent prospect for the primary prevention of cervical cancer. The bivalent and quadrivalent vaccines are both available in India. The nonavalent vaccine is licensed but not yet available. However, there still remain controversies regarding the vaccination of older women, immunocompromised females and other special groups. To provide recommendations for HPV vaccination in India. The Federation of Obstetric and Gynecological Societies of India (FOGSI) convened an expert group on cervical cancer prevention to formulate good clinical practice recommendations (GCPR) with respect to vaccine efficacy and safety, target groups, optimal timing and dosing schedules. HPV vaccines are licensed for females aged 9-45 years in India and have been seen to be safe and effective. FOGSI recommends HPV vaccination of all girls <15 years of age as the best target group, in whom two-doses at an interval of 6 months, extendable to 18 months, are recommended. Three-doses are recommended in girls >15 years of age, immunocompromised persons and sexual assault survivors. Older women and women with abnormal screening results may be vaccinated with an understanding that vaccination does not protect against already acquired infections and screening has to continue. Single-dose vaccination results are promising. Increased awareness is required to reduce vaccine hesitancy. HPV vaccination should be the priority to achieve the elimination of cervical cancer. The introduction of affordable HPV vaccines and reduced dose schedules will improve coverage.

Screening and management of preinvasive lesions of the cervix: Good clinical practice recommendations from the Federation of Obstetrics and Gynaecologic Societies of India (FOGSI).

In India, there are marked variations in resources for cervical cancer screening. For the first time, resource-stratified screening guidelines have been developed that will be suitable for low middle-income countries with similar diversities. The current article describes the process and outcomes of these resource stratified guidelines for screening and treatment of preinvasive lesions of cervix. Evidence from literature was collated and various guidelines were reviewed by an expert panel. Based on the level of evidence, guidelines were developed for screening by human papillomavirus (HPV) testing, cytology and visual inspection after application of acetic acid (VIA), and management of screen positive lesions in different resource settings. Expert opinion was used for certain country-specific situations. The healthcare system was stratified into two resource settings - good or limited. The mode of screening and treatment for each was described. HPV testing is the preferred method for cervical cancer screening. VIA by trained providers is especially suitable for low resource settings until an affordable HPV test becomes available. Healthcare providers can choose the most appropriate screening and treatment modality. A single visit approach is encouraged and treatment may be offered based on colposcopy diagnosis ('see and treat') or even on the basis of HPV test or VIA results ('screen and treat'), if compliance cannot be ensured. The Federation of Obsterician and Gynaecologists of India Good Clinical Practice Recommendations (FOGSI) GCPR are appropriately designed for countries with varied resource situations to ensure an acceptable cervical cancer prevention strategy.

Facility preparedness for an obstetric unit during the Covid-19 pandemic.

Covid-19 infection has placed health systems under unprecedented strain and foresight for preparedness is the key factor to avert disaster. Every facility that provides obstetric service needs a certain level of preparedness to be able to handle at least Covid-suspect pregnant women awaiting test reports, who need to be managed as Covid-positive patients till reports are available. Thus, these facilities need to have triage areas and Covid-suspect labour rooms. Healthcare facilities can have designated areas for Covid-positive patients or have referral linkages with designated Covid-positive hospitals. Preparation includes structural reorganization with setting up a Covid-suspect and Covid-positive facility in adequate space, as well as extensive training of staff about infection control practices and rational use of personal protective equipment (PPE). A systematic approach involving five essential steps of making standard operating procedures, infrastructural reorganization for a triage area and a Covid-suspect labour ward, procurement of PPE, managing the personnel and instituting appropriate infection control practices can ensure uninterrupted services to patients without compromising the safety of healthcare providers.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Concordance of glycaemic and cardiometabolic traits between Indian women with history of gestational diabetes mellitus and their spouses: an opportunity to target the household.

AIMS/HYPOTHESIS: The aim of this study was to investigate the concordance of dysglycaemia (prediabetes or diabetes) and cardiometabolic traits between women with a history of gestational diabetes mellitus (GDM) and their spouses. METHODS: Using hospital medical records, women with GDM (diagnosed between 2012 and 2016) and their spouses were invited to participate in the study and to attend a scheduled hospital visit in a fasting state. Sociodemographic, anthropometric and medical data were collected, and a 75 g OGTT with serum insulin estimation, HbA1c measurement and fasting lipid profile were performed at the visit. Prediabetes and diabetes were defined using ADA criteria and the metabolic syndrome was defined using IDF criteria. RESULTS: A total of 214 couples participated in the study. Women were tested at a mean ± SD age of 32.4 ± 4.6 years and median (quartile [q]25-q75) of 19.5 (11-44) months following the index delivery, while men were tested at a mean ± SD age of 36.4 ± 5.4 years. A total of 72 (33.6%) couples showed concordance for dysglycaemia, while 99 (46.3%) and 51 (23.8%) couples were concordant for overweight/obesity and the metabolic syndrome, respectively. A total of 146 (68.2%) couples showed concordance for any of the above three factors. The presence of dysglycaemia in one partner was associated with an increased risk of dysglycaemia in the other partner (OR 1.80 [95% CI 1.04, 3.11]). Similarly, being overweight/obese (OR 2.19 [95% CI 1.22, 3.93]) and presence of the metabolic syndrome (OR 2.01 [95% CI 1.16, 3.50]) in one partner was associated with an increased risk of these conditions in the other partner. Both women and men were more likely to have dysglycaemia if they had a partner with dysglycaemia. Women with a partner with dysglycaemia had a significantly higher BMI, waist circumference and diastolic BP, and a significantly higher probability of low HDL-cholesterol (<1.29 mmol/l) and the metabolic syndrome compared with women with a normoglycaemic partner. No such differences were observed for men with or without a partner with dysglycaemia. CONCLUSIONS/INTERPRETATION: The high degree of spousal concordance found in this study suggests social clustering of glycaemic and cardiometabolic traits among biologically unrelated individuals. This provides us with an opportunity to target the behavioural interventions at the level of the 'married couple', which may be a novel and cost-effective method of combating the current diabetes epidemic.

Comparison of ferric Carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy- randomised controlled trial.

BACKGROUND: To evaluate the efficacy and safety of intravenous Ferric Carboxymaltose. (FCM) in comparison with intravenous Iron sucrose complex (ISC) for treatment of iron deficiency anemia in pregnancy. METHODS: A randomized clinical trial was conducted from (January 2016-August 2017). at a tertiary hospital. Pregnant women diagnosed with moderate to severe iron deficiency anaemia were screened for the study. One hundred patients were randomized to receive either intravenous FCM or ISC. Primary outcome was rise in hemoglobin (Hb) from baseline after 12 weeks. Secondary outcomes were change in RBC indices, serum iron studies, improvement in fatigue scores, number of visits and perinatal outcome. RESULTS: Mean rise in Hb at 12 weeks was significantly higher in FCM group (29 g/L vs 22 g/L; p value < 0.01). FCM was associated with greater improvement in fatigue scores. Number of visits were significantly less in FCM group. No serious adverse events were noted in either group. CONCLUSION: Treatment with FCM resulted in rapid replenishment of iron stores in pregnant women with significantly higher Hb rise over a 12 week period. The convenient dosing with lesser number of total doses to complete the treatment will lead to better compliance in community setting. CLINICAL TRIAL REGISTRATION ( WWW.CTRI.NIC.IN ): CTRI/2015/09/006224. Registered on 21/07/2017 (Trial registered retrospectively).

Oral metronomic chemotherapy for recurrent & refractory epithelial ovarian cancer: A retrospective analysis.

Background & objectives: Advanced epithelial ovarian cancer (EOC) is associated with dismal outcome and progression-free survival (PFS) shortens with each subsequent relapse. For patients with recurrent and platinum refractory disease, therapeutic options are limited. Oral metronomic therapy (OMT) is associated with symptomatic relief and stable response in a significant proportion of patients. We retrospectively evaluated the outcome of patients with EOC treated with OMT at a tertiary care hospital in north India. Methods: Between January 2011 to December 2017, 36 EOC patients received OMT. Patients' median age was 50 yr (range, 38-81 yr) and they had received a median of two lines of prior chemotherapy. OMT regimen included a combination of cyclophosphamide, etoposide (VP-16) and celecoxib with or without pazopanib along with supportive care. Response rates and outcomes were ascertained using the Gynecological Cancer Intergroup Guidelines. The toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03. Results: The median CA-125 before initiating OMT was 160 U/ml (range, 42.23-5330 U/ml). The median interval between last chemotherapy and starting OMT regimen was 159 days (range, 1-1211 days). The overall response rate was 50 per cent. The median progression-free survival (PFS) was 8.2 months [95% confidence interval (CI): 5.03-10.33], and the median overall survival was 38 months (95% CI: 25.6-NR). Patients who received two lines of chemotherapy before OMT (P=0.052) and those who received pazopanib-based OMT (P=0.0513) had better PFS. Interpretation & conclusions: For patients with relapse and refractory EOC, OMT could be a reasonable option. A combination of oral etoposide (VP-16) and pazopanib needs further evaluation in a large number of patients in a randomized trial.

Correlation of body mass index (BMI), anti-mullerian hormone (AMH), and insulin resistance among different polycystic ovary syndrome (PCOS) phenotypes - a cross-sectional study.

One hundred and fifty infertile polycystic ovary syndrome (PCOS) women were classified into four phenotypes on the basis of Rotterdam criteria. Homeostatic model assessment of insulin resistance (HOMA-IR) with a cutoff ≥2.5 was considered as a measure of insulin resistance (IR). Maximum number of patients, 57 (38%) in our cohort belonged to phenotype A or the classical phenotype with all 3 features of Rotterdam criteria. Mean body mass index (BMI) in all phenotypes was more than 25 kg/m2 and the highest was seen in phenotype B. According to BMI categories in the four phenotypes, more number of women was in the obese category in phenotype A (24.5%) and B (56.5%) in comparison to phenotype C (18.2%) and D (10.8%) (p<.001). There was no difference in median HOMA-IR among different phenotype categories (p=.718). The median value of anti-mullerian hormone (AMH) was highest in phenotype A (11.68 ng/ml [7.94-16.46]) and significantly more in comparison to B phenotype (Kruskal-Wallis, p=.018). Thus there is heterogeneity in AMH levels and BMI in different PCOS phenotypes with higher levels in the most severe phenotypes. There is, however, no correlation of IR among the different phenotype groups and further investigation is needed to characterize its role in phenotypic classification.

Effect of intracameral human cord blood-derived stem cells on lasered rabbit trabecular meshwork.

BACKGROUND: This study aimed to investigate the effect of intracameral human cord blood stem cells on lasered rabbit trabecular meshwork. METHODS: Immediately following diode laser application to the trabecular meshwork, human cord blood stem cells were injected intracamerally, in one eye of 12 albino rabbits. The other eye of ten rabbits was lasered controls and two eyes were normal controls. Rabbits were killed after 4, 8 and 12 weeks. RESULTS: Lasered control rabbit eyes showed significant disruption of trabecular architecture, loss and pleomorphism of trabecular endothelial cells and progressive narrowing of trabecular spaces till 12 weeks. In contrast, lasered eyes, concurrently injected with human cord blood stem cells, showed relatively preserved endothelial cellularity and structure of the trabecular meshwork, at all time points. Human CD34- and CD44-positive cells were identified in 7/8 eyes treated with stem cells, at 4 and 8 weeks, and 2 of 3 at 12 weeks. Many PKH26-labeled human cord blood cells were visible throughout the trabecular area at 4 weeks. They gradually decreased in number by 8 weeks, and at 12 weeks, they appeared to be oriented along trabecular beams. CONCLUSIONS: There was a relative preservation of cellularity and architecture of the trabecular meshwork in eyes injected with human cord blood stem cells, as compared to lasered control eyes up to 12 weeks, without significant inflammation. This suggests a probable role for such stem cells in eyes with glaucoma, having trabecular dysfunction.