Diagnostic and management dilemmas of pregnancies at the utero-tubal junction: A case series and management algorithm.

OBJECTIVE: A pregnancy at the utero-tubal junction is a rare type of ectopic pregnancy and is associated with high maternal morbidity if it remains undetected. In the present study we discuss four cases of ectopic pregnancies at the utero-tubal junction which caused diagnostic and management dilemmas. METHODS: Four cases of early pregnancies with the gestational sac (G-sac) implanted near the utero-tubal junction are described. In case 1 this was suspected after a failed attempt at dilatation and curettage at our hospital, cases 2 and 3 presented with amenorrhea and pain abdomen and case 4 was diagnosed on first pregnancy documentation scan after frozen embryo transfer. RESULTS: As initial two-dimensional (2D) transvaginal scan (TVS) failed to diagnose the exact location of the G-sac, three-dimensional (3D) TVS helped to localize the exact location of pregnancy and subsequent individualized management. Case 1 had a partial intramural ectopic pregnancy managed by laparotomy and removal of the ectopic sac. The second and third cases were eccentric uterine pregnancies. The fourth was an interstitial ectopic pregnancy managed by a laparoscopic loop and stitch technique. CONCLUSION: This case series describes the role of 3D TVS for the evaluation of pregnancies implanted at the utero-tubal junction and individual management of eccentric intrauterine, interstitial ectopic and intramural ectopic pregnancies. A diagnostic algorithm for such types of cases and management options is discussed.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

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.

Utility of Visceral Adiposity Index and Lipid Accumulation Products to Define Metabolically-Unhealthy Polycystic Ovary Syndrome in Asian Indian Women - A Cross Sectional Study.

Background: Polycystic ovary syndrome (PCOS) women are at risk of developing diabetes, cardiovascular disease and metabolic syndrome (MetS) due to insulin resistance (IR) and hyperandrogenism (HA). Both visceral adiposity index (VAI) and lipid accumulation product (LAP) are simple outpatient department-based metric tools that have been introduced to screen PCOS women who are metabolically unhealthy and are at risk of development of MetS. Aims: The aim of the study was to evaluate VAI and LAP in women with PCOS and to correlate them with metabolic and endocrine markers. The study also assessed these parameters amongst different PCOS phenotypes and determined their usefulness to define metabolically healthy PCOS (MH-PCOS) and metabolically unhealthy PCOS (MU-PCOS). Settings and Design: The design of the study was a cross-sectional study. Materials and Methods: Two hundred PCOS women were included in the study, and all the clinical, anthropometric, hormonal, biochemical and metabolic markers were assessed. The cohort was divided into MH-PCOS and MU-PCOS by the modified National Cholesterol Education Programme criteria. VAI and LAP were calculated and correlated with clinical, endocrine and metabolic parameters. Statistical Analysis Used: Univariate and multivariate logistic regression analysis was used to study the independent role of VAI and LAP to predict MetS. Adjusted and unadjusted odds ratios were calculated. Receiver-operating characteristic (ROC) analysis was done to define cut-offs in Asian Indian women. Results: VAI and LAP had good ability to correctly discriminate MU-PCOS from MH-PCOS (area under the curve [AUC] [95% confidence interval (CI)]: 0.89 [0.82-0.95]) and (AUC [95% CI [0.81-0.92] =0.86) using ROC, respectively. The sensitivity of VAI and LAP corresponding to the optimal cut-off of ≥2.76 and ≥48.06 (Youden) was 84.09% and 79.55%, respectively. Similarly, the specificity of VAI and LAP was 85.26% and 79.49%, respectively. VAI has a positive predictive value of 61.7% (95% CI [23.7%-40.3%]) and a negative predictive value of 95% (95% CI [88%-99.1%]). LAP has a positive predictive value of 53% (95% CI [40.3%-65.4%]) and a negative predictive value of 93.3% (95% CI [87.6%-96.9%]). PCOS women having VAI ≥ 2.76 had 19.3 times ([95% CI: 6.50-57.70]) more chance of developing MetS. PCOS women having LAP (≥48.06) have 3.7 times ([95% CI: 1.35-10.60]) more odds. There was no difference between ROC curves of VAI and LAP (P = 0.32). Conclusion: VAI cut-off ≥ 2.76 and LAP with a cut-off of ≥ 48.06 may be used as markers for predicting MetS amongst PCOS women.

Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India.

OBJECTIVE: Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS: A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS: Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION: FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

OBJECTIVES: The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. METHODS: This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. RESULTS: Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. CONCLUSION: Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

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.

Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization.

INTRODUCTION: Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(H2S)/Rho GTPase Rac1 axis. This novel role of H2S and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells. METHODS: Placental tissues were obtained post-delivery from consented preeclamptic and normotensive mothers (n = 60). The protein expression levels of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) along with its downstream migratory molecules were compared in both the arms. The pro-migratory role of H2S was investigated in a first trimester placental cell line. RESULTS: H2S promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of H2S producing enzymes in the PE placentae along with decreased levels of Rho GTPases (Rac1 and Rho A) corroborate the results of PAG and AOAA treatment in down regulating the Rho GTPases in the in vitro grown placental cultures. Reduction of the migratory potential of trophoblastic cells caused due to hypoxia/reoxygenation was rescued by upregulating the H2S expression with the use of NaHS as a H2S donor. DISCUSSION: Exogenous H2S increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. H2S as a gaso-transmitter holds a great potential as a therapeutic agent. Its long-term effects need to be investigated using model systems (rat/mouse) of PE following it up with clinical regulatory trials.

The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.

AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).

Expression of DKK1 in Endometrial Endometrioid Carcinoma and Its Correlation with Wnt/ß-catenin Signalling Pathway.

Objectives: Endometrial cancer is the most prevalent form of cancer affecting female reproductive organs. The most common histologic type, endometrioid carcinoma, accounts for 75-80% of all endometrial cancer cases. Studies on DKK1 expression profiles and their inhibitory role in the Wnt signalling pathway in the genesis and development of endometrial carcinoma are scarce. This study aimed to investigate DKK1 expression in endometrial carcinoma and its correlation with the Wnt/ß-catenin pathway. Methods: A total of 160 formalin-fixed paraffin-embedded samples were included in this study (50 cases of endometrial atypical hyperplasia, 50 cases of endometrioid endometrial carcinoma, 30 cases of proliferative endometrium and 30 cases of secretory endometrium). The expression patterns of DKK1, E-cadherin, ß-catenin and c-Myc in endometrial atypical hyperplasia and carcinoma were investigated and compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July 2018 to June 2020. Results: A decreasing pattern of immunopositivity for DKK1, E-cadherin and ß-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma was found. Increasing c-Myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing DKK1 immunopositivity was well correlated with E-cadherin, ß-catenin and c-Myc immunopositivity. Conclusion: Decreasing DKK1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of DKK1 in endometrioid carcinoma. DKK1 is downregulated in the Wnt signalling pathway in endometrioid endometrial carcinoma. Therefore, DKK1 is promising as a biomarker for screening endometrioid carcinoma. Future studies should examine the reactivation of the DKK1 gene, which may be a valuable strategy for antagonising the Wnt signalling pathway.

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.

Comparison of Cumulative Live Birth Rate (CLBR) According to Patient Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Stratification Among Low Prognosis Women Undergoing IVF-ICSI Cycles.

Background: The purpose of the current study was to evaluate patient-oriented strategies encompassing individualized oocyte number (POSEIDON) criteria, validate stratification of low prognosis women, and prognosticate their reproductive potential in terms of cumulative live birth rate (CLBR) in Indian women. Methods: Out of 4048 women who underwent IVF/ICSI, 3287 women met the criteria for final evaluation of CLBR. They criteria were divided into (a) group 1a as cases with <4 oocytes retrieved and 1b with 4-9 oocytes retrieved; (b) group 2a as cases with <4 oocytes retrieved and 2b with 4-9 oocytes retrieved; (c) group 3 (<35 years, AMH <1.2 ng/ml, AFC <5); and (d) group 4 (≥35 years, AMH <1.2 ng/ml, AFC <5). Non-POSEIDON group was sub-divided into normo-responders (10-20 oocytes) and hyper-responder (>20 oocytes). Results: Overall CLBR was two-fold lower in POSEIDON group as compared to non-POSEIDON group (p<0.001). For every one-year increase in the age, the odds of CLBR decreased by 4% (OR 0.96, CI 0.93-0.99) in POSEIDON group and by 5% (OR 0.95, CI 0.92-0.98) in non-POSEIDON group. For every unit increase in number of oocytes retrieved, the odds of CLBR increased by 1.22 times (OR1.22, CI 1.16-1.28) in POSEIDON group and by 1.08 times (OR 1.08, CI 1.05-1.11) in non-POSEIDON group. Among POSEIDON groups, the highest values in CLBR belonged to group 1b followed by 3, 2b, 4, 1a, and 2a. Conclusion: POSEIDON stratification of low-prognosis women undergoing IVF may be considered valid to prognosticate and counsel women undergoing IVF. Prospective studies will strengthen its validity among different ethnic populations.

Cardiometabolic profile of women with a history of overt diabetes compared to gestational diabetes and normoglycemia in index pregnancy: Results from CHIP-F study.

PURPOSE: We aimed to evaluate the prevalence of postpartum diabetes among women with a history of overt diabetes in pregnancy (ODiP) and compare with women having a history of gestational diabetes mellitus (GDM) and normoglycemia in pregnancy. METHODS: We have an established longitudinal cohort of postpartum women with a history of hyperglycemia (preexisting diabetes [PED] [n = 101], ODiP [n = 92], GDM [n = 643]), and normoglycemia (n = 183) in pregnancy. For this study, we excluded women with PED and invited other eligible women in a fasting state for clinical and biochemical evaluation. RESULTS: We evaluated 918 women with a mean (SD) age of 33.6 (5.0) years and at a median (interquartile range) postpartum interval of 31 (20-45) months. Diabetes was diagnosed in 65 (70.7%) women in ODiP compared to 99 (15.4%) in GDM (p < .001) and 4 (2.2%) in normoglycemia group (p < .001). In the ODiP group, the prevalence of diabetes was 47.4% among women tested in the first year postpartum, increasing to 86.8% among women tested at >3 years postpartum. Diabetes was more common when ODiP was diagnosed in the first (27/29, 93.1%) compared to the second trimester of pregnancy (35/57, 61.4%). The adjusted odds ratio for diabetes in ODiP was 14.82 (95% confidence interval, 8.49-25.87; p < .001; reference category: GDM). CONCLUSIONS: The prevalence of postpartum diabetes was significantly higher in women with ODiP compared to GDM. Nearly 50% of women with ODiP did not develop diabetes in the first year of follow-up, especially when ODiP was diagnosed after the first trimester of pregnancy and on the basis of a 2-h oral glucose tolerance test value. Such women are amenable to prevention strategies.

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.

Robert's Uterus versus Juvenile Cystic Adenomyoma - Diagnostic and Therapeutic Challenges - Case Report and Review of Literature.

This case report highlights the diagnostic dilemma and therapeutic challenges encountered while managing adolescent girls with progressive dysmenorrhoea and management of Robert's uterus. Two girls aged 20 years and 13 years presented with severe progressive dysmenorrhoea. In the first case, laparoscopy revealed juvenile cystic adenomyoma (JCA) of 3 cm × 3 cm on the left side anteroinferior to the round ligament. Laparoscopic resection of the lesion was done, and histopathology revealed features of adenomyosis. In the second case, there was a globular enlargement of the right half of the uterine body with round ligament and adnexa attached to the lesion (Robert's uterus). In view of severe symptoms, complete resection of the lesion and partial resection of hemi-uterus was done, followed by myometrial defect closure. Both cases were initially diagnosed as JCA, and the final diagnosis was made on laparoscopy. Both girls had complete symptomatic relief from the next menstrual cycle and have been under follow-up for 24 months and 18 months, respectively. Due to the rarity of conditions, Robert's uterus and JCA are usually misdiagnosed with each other or with other Mullerian anomalies such as a non-communicating unicornuate uterus. Radiologists and clinicians should be aware of these different pathologies causing similar symptoms. Understanding the pathology, early diagnosis, timely referral and correct surgical procedure are emphasised to improve reproductive outcomes.

Augmenting the Angiogenic Profile and Functionality of Cord Blood Endothelial Colony-Forming Cells by Indirect Priming with Bone-Marrow-Derived Mesenchymal Stromal Cells.

Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.

Comparison of Accuracy of Freestyle Libre Pro and Medtronic iPro2 Continuous Glucose Monitoring Systems in Pregnancy.

There are limited data on head-to-head performance of Freestyle Libre Pro (FSL-Pro) and blinded Medtronic iPro2 continuous glucose monitoring system in pregnancy. In this prospective observational study, women with hyperglycemia in pregnancy (n = 42) underwent simultaneous FSL-Pro and Medtronic iPro2 sensor insertion and self-monitoring of blood glucose using Contour Plus meter (reference). The overall mean absolute relative difference (MARD) for iPro2 and FSL-Pro systems were 8.0% ± 9.2% and 19.0% ± 12.7%, respectively. At hypoglycemic range, both sensors performed less accurately (MARD: 18.0% and 16.8%, respectively), whereas iPro2 showed higher accuracy at euglycemic (8.2% and 19.3%, respectively) and hyperglycemic (6.8% and 18.0%, respectively) ranges. On Bland-Altman analysis, iPro2 and FSL-Pro underestimated glucose by 0.01 and 1.09 mmol/L, respectively. The ISO criteria were fulfilled for 88.5% and 44.9% of all values, respectively. To conclude, iPro2 was more accurate; however, both sensors demonstrated inaccuracy at hypoglycemic range, highlighting the need for refinements in the current generation of sensors to address this problem.