Prevention of nodules and enhancement of antibody response to genetically engineered recombinant vaccine against Human Chorionic Gonadotropin (hCG) for contraception.

Objective: Human Chorionic Gonadotropin (hCG) plays a crucial role in embryo implantation and in maintenance of pregnancy. An immuno-contraceptive approach involves the use of a recombinant hCGß-LTB vaccine formulated with adjuvant Mycobacterium indicus pranii (MIP), to prevent pregnancy without disturbing ovulation, hormonal profiles, and menstrual cycles in women. The present work in mice was designed to address issues encountered in clinical trials conducted with hCGß-LTB vaccine, with focus on two primary concerns. Firstly, it aimed to determine the optimal vaccine dosage required to induce a high level of anti-hCG antibodies. Secondly, it aimed to assess the safety profile of the vaccine, specifically injection site reactions in the form of nodules, observed in some of the subjects.Methods and Results: Studies undertaken indicate that a 2 µg dose of the protein version of the vaccine, administered in mice through the intramuscular route, can induce high anti-hCG titres. Furthermore, administering a booster dose enhances the antibody response. Our findings suggest that the concentration and frequency of administration of the adjuvant MIP can also be reduced without compromising vaccine efficacy.Conclusion: The issue of nodule formation at the injection site can be mitigated either by administering the vaccine along with MIP intramuscularly or injecting hCG vaccine and MIP at separate intradermal sites. Thus, protein vaccine administered at a 2µg dose via the intramuscular route addresses both efficacy and safety concerns.

The Phase I/II clinical trials initiated with the recombinant hCG vaccine in women revealed inadequate antibody titres in all subjects, alongside the development of nodules at the injection sites in some participants. Studies were undertaken in mice to propose potential strategies for mitigating injection site reactions and enhancing the antibody response. It was concluded that the optimum dose of the protein version of the vaccine to get high antibody titres, is 2 µg administered intramuscularly while upholding safety standards.

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.

SCOPE: Surveillance of COVID-19 in pregnancy- results of a multicentric ambispective case-control study on clinical presentation and maternal outcomes in India between April to November 2020.

OBJECTIVE: To determine the clinical manifestations, risk factors, treatment modalities and maternal outcomes in pregnant women with lab-confirmed COVID-19 and compare it with COVID-19 negative pregnant women in same age group. DESIGN: Multicentric case-control study. DATA SOURCES: Ambispective primary data collection through paper-based forms from 20 tertiary care centres across India between April and November 2020. STUDY POPULATION: All pregnant women reporting to the centres with a lab-confirmed COVID-19 positive result matched with controls. DATA QUALITY: Dedicated research officers extracted hospital records, using modified WHO Case Record Forms (CRF) and verified for completeness and accuracy. STATISTICAL ANALYSIS: Data converted to excel files and statistical analyses done using STATA 16 (StataCorp, TX, USA). Odds ratios (ORs) with 95% confidence intervals (CI) estimated using unconditional logistic regression. RESULTS: A total of 76,264 women delivered across 20 centres during the study period. Data of 3723 COVID positive pregnant women and 3744 age-matched controls was analyzed. Of the positive cases 56·9% were asymptomatic. Antenatal complications like preeclampsia and abruptio placentae were seen more among the cases. Induction and caesarean delivery rates were also higher among Covid positive women. Pre-existing maternal co-morbidities increased need for supportive care. There were 34 maternal deaths out of the 3723(0.9%) positive mothers, while covid negative deaths reported from all the centres were 449 of 72,541 (0·6%). CONCLUSION: Covid-19 infection predisposed to adverse maternal outcomes in a large cohort of Covid positive pregnant women as compared to the negative controls.

A 5-year comparative study of efficacy and acceptability of three different sizes of TCu380Ag and TCu380A intrauterine devices.

BACKGROUND: The intrauterine contraceptive device TCu380Ag when compared with TCu380A at 1 year of use had better acceptability and continuation rates. OBJECTIVES: To study the continuation rate, efficacy, and acceptability of TCu380Ag in three sizes versus TCu380A at 5 years of use. METHODS: A total of 600 women opting for intrauterine contraceptive devices were randomized equally into two groups. Group 1 received the TCu380Ag device (Normal, Maxi, and Mini for uterocervical length 7-8.5 cm, 8-9 cm, and 6-7.5 cm, respectively) and Group 2 received the TCu380A device. Follow-up was performed at 5 years to assess efficacy, acceptability, and continuation. Frequency data comparisons was performed across categories using χ2 /Fisher exact test. RESULTS: At 5 years of use, Kaplan-Meier survival analysis showed that TCu380Ag compared with TCu380A had a higher continuation rate (45% vs. 35%, P = 0.010) with 100% efficacy each. TCu380Ag had fewer side effects, including heavy menstrual bleeding (16.6% vs. 34.1%, P < 0.001), abdomen pain (12.1% vs. 23.0%, P = 0.001), and expulsions (4.4% vs. 8.7%, P < 0.050), and fewer discontinuations attributable to contraceptive side effects (42.7% vs. 56.9%, P = 0.012). The mini TCu380Ag had the highest continuation rates and least menstrual irregularity (P < 0.050). CONCLUSIONS: The TCu380Ag device in three sizes is an alternative to TCu380A for women desiring 5 years of contraception with equal efficacy, better continuation, and acceptability. The mini size is preferred for women with a uterocervical length of 6 to 7.5 cm.

"Association of Leptin with Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis".

BACKGROUND: Serum leptin has been considered as an important measurable diagnostic and prognostic biomarker for polycystic ovarian syndrome (PCOS), although its evidence for use in clinical practice is limited. We aim to synthesize the available evidence on the clinical use of serum leptin values in PCOS by doing a systematic review and meta-analysis of studies. OBJECTIVE: To conduct a meta-analysis to determine the pooled effect size of the association of leptin levels in patients with PCOS. METHODS: We searched electronic databases, i.e., PubMed, Google Scholar, Web of Science, ClinicalTrials.gov, and Medline from inception to September 2020, keeping filters for human studies and published in the English language. We used the random-effects model if heterogeneity between the studies was > 50%; otherwise, a fixed-effect model was applied to determine the standardized mean difference with 95% CI for comparison of leptin level between cases and controls. All the statistical analyses were completed using software STATA version 13. RESULTS: The meta-analysis included a total of 35 studies involving 2015 cases and 1767 controls that suggested statistically significantly higher leptin levels in the women with PCOS as compared to controls (SMD, 1.76, 95% CI 1.28 to 2.23, P < 0.001). In the stratified analysis when only high methodological quality studies were included, we did not observe a statistically significant difference in the leptin level between PCOS and controls (SMD 0.68, 95% CI -0.09 to 1.46). Analysis restricted to low methodological quality studies observed statistically significant high leptin levels in PCOS women as compared to controls (SMD 2.24, 95% CI 1.65 to 2.83). CONCLUSION: The available evidence suggests that elevated leptin levels may be associated with risk of PCOS as compared to controls; however, failure to observe the similar association in high methodological quality studies demands further well-designed adequately powered studies to validate the findings.

A 1-year comparison of TCu380Ag versus TCu380A intrauterine contraceptive devices in India.

OBJECTIVE: To compare TCu380Ag and TCu380A intrauterine contraceptive devices after 1 year of use. METHODS: A prospective randomized controlled trial was conducted among healthy married women aged 20-35 years who attended the family planning clinics of three tertiary centers in India between August 1, 2015, to March 31, 2018. The TCu380Ag group (n=300) received one of three sizes of this device depending on uterocervical length: maxi (8.0-9.0 cm), normal (7.0-8.5 cm), or mini (6.0-7.5 cm). The remaining 300 participants received TCu380A. Follow-up was conducted at 3-monthly intervals to assess continuation rate, acceptability, efficacy, adverse effects, and complications. RESULTS: The TCu380Ag group had a higher continuation rate than the TCu380A group at 1 year (84.0% vs 75.8%; P=0.01), with an efficacy of 99.6% versus 100.0% (P>0.05). Overall estimated continuation rates were 94.5% (95% confidence interval [CI] 91.7%-96.4%) and 88.4% (95% CI 83.2%-91.5%), respectively (P=0.026). Use of TCu380Ag was associated with fewer adverse effects (heavy menstrual bleeding, abdominal pain, or expulsion) when compared with TCu380A (P>0.05 for all comparisons). Discontinuation rates owing to adverse effects were 6.59% for TCu380Ag versus 13.26% for TCu380A (P=0.01). CONCLUSIONS: Varying sizes of TCu380Ag could provide an alternative to TCu380A.

Assessment and comparison of pregnancy outcome among anaemic and non anaemic primigravida mothers.

BACKGROUND: Primigravidas (PGs) are high-risk women and anemia in pregnancy is one of the commonest causes of maternal morbidity and mortality. OBJECTIVES: The study was conducted to assess impact of anemia on course and outcome of pregnancy in anemic (Hemoglobin 8-10.9 gm%) and nonanemic PGs. METHODS: This prospective longitudinal study was conducted in All India Institute of Medical Sciences, New Delhi. PGs 20-30 years age, gestation age 16-18 weeks, hemoglobin >8 gm%, live singleton pregnancy, and no other medical illness were recruited after informed consent. The women were Grouped 1 and 2 if hemoglobin was ≥11 gm% and 8-10.9 gm%, respectively. Complete hemogram done at enrollment, 28-30 weeks of pregnancy and 6 weeks postdelivery. Obstetric outcome and presence of anemia postdelivery were compared between groups using Chi-square test and Fisher's exact test. RESULTS: A total of 377 PGs were enrolled and obstetric outcomes studied in 179 (Group 1) and 149 (Group 2) excluding women who did not complete study. There was no statistically significant difference in baseline characteristics, antenatal complications, gestational age, mode of delivery, and neonatal outcome. At 28-30 weeks of gestation, in spite of iron supplementation higher percentage (64.4%) (P < 0.05) of anemic patients remained anemic. At 6 weeks postdelivery, 15.6% and 24.2% were anemic in Group 1 and 2, respectively (P > 0.05). The adverse postpartum events (7.6%) were seen more in anemic compared to nonanemic pregnant women (P < 0.05). CONCLUSIONS: Cautious approach required in postpartum period of anemic women though antenatal period is similar as nonanemic pregnant women.

Temporal trends of malondialdehyde in stored human plasma.

Malondialdehyde (MDA) is widely used as oxidative stress biomarker in biomedical research. Plasma is stored in deep freezers generally till analysis. Effect of such storage on MDA values, which may be variable and prolong, was incidentally observed in the ongoing study which is to estimate oxidative stress with oral iron. Plasma from blood samples of pregnant women (20-30 years age) in third trimester of singleton pregnancy (n = 139), consuming oral iron tablets was stored at -20 °C with intention of MDA estimation, as soon as possible. However logistic problems led this storage for prolonged and variable period (1-708 days). When values of MDA estimated using "Ohkawa" 79 method and readings were plotted against time to check the temporal effect, it showed a hyperbolic curve. Standard deviation (SD) was lowest when samples were tested within 3 weeks time. The samples analyzed within 3 weeks had mean ± SD value of 31.59 ± 26.11 µmol/L, while 123.7 ± 93.97 and 366.5 ± 189.8 µmol/L for samples stored for 1-3 and 4 months to 1 year respectively. Mean ± SD were 539.9 ± 196.8 in the samples store for more than a year. Rate of change in values was also lowest (0.0433 µmol/L/day) in the samples tested within first 3 weeks, which rose to 1.2 µmol/L/day during 3 month's storage. This rate peaked at storage of 120 days (1.87 µmol/L/day) and fell to 0.502 µmol/L/day in the second year of storage. It is concluded that at -20 °C, only 3 weeks of storage time should be considered valid for fairly acceptable stability in MDA values.

Cervical priming with misoprostol before manual vacuum aspiration versus electric vacuum aspiration for first-trimester surgical abortion.

OBJECTIVE: To compare the efficacy of manual vacuum aspiration (MVA) with electric vacuum aspiration (EVA) and to evaluate whether cervical priming with misoprostol facilitates cervical dilation and reduces complications associated with first-trimester medical abortion performed up to 10 weeks of pregnancy. METHODS: A total of 600 women who requested termination of pregnancy were randomized into 4 groups (150 women in each group). Group I and II received a vaginal placebo 3 hours before MVA or EVA, respectively. Group III and IV received 400 µg of vaginal misoprostol 3 hours before MVA or EVA, respectively. RESULTS: Complete abortion rates after MVA and EVA were both 97.9%; after cervical priming with misoprostol complete abortion rates were 98.6% versus 97.3% after cervical priming with placebo (P>0.05). Administration of misoprostol into the vagina before MVA resulted in 99.3% complete abortions (P=0.40), and the least operative blood loss, operating time, and need for cervical dilation (P<0.05). Overall complications and adverse effects were similar in all groups (P>0.05). CONCLUSION: For surgical evacuation, EVA and MVA did not differ in efficacy. Cervical priming 3 hours before MVA for termination of pregnancy significantly reduced the need for cervical dilation and the operative time, and improved the efficacy of the procedure. Pretreatment with vaginal misoprostol before MVA is a safe and effective method for terminating pregnancies of up to 10 weeks of gestation. CLINICAL TRIALS REGISTRY: CTRI/2009/091/000008.

Socio-demographic profile of women undergoing abortion in a tertiary centre.

INTRODUCTION: Induced abortion is the most controversial area of family planning and it is often the most important method of fertility regulation by a community to control family size. Although abortion has been greatly liberalized, the annual number of legal abortions performed in India is 0.5 million of the annual estimated 6 million abortions. MATERIAL AND METHODS: This cross-sectional, descriptive, population based study of the socio-demographic profile of women was conducted between March and August 2007 in the Family Planning Clinic at AIIMS, New Delhi. An ethical clearance was obtained and informed written consent taken from both the partners. Hundred and eighty women requesting an abortion were eligible for inclusion. RESULTS: Mean age of the participants was 29.2 years (range SD+/-3.5) and mean parity was 2.8 (range 1-6, SD+/-0.9). Thirty-four percentage of women reported a previous abortion in the preceding 2 years. 52.5% of women whose present pregnancy was unintended had used a highly effective form of contraception 6 months before the event, like oral contraceptive pill (18.2%), condoms (36.8%), withdrawal method (32.5%) or periodic abstinence (12.1%). The reasons cited for termination of pregnancy were unplanned pregnancy 32.8% women, inadequate income 24.6%, family complete 20.3% and contraceptive failure 22.3%. The vast majority of women were uneducated (34.8%) with 31.4% having passed high school and above while 33.8% had left their education before completing high school. CONCLUSION: In a country like India with its vast population women in their reproductive age-group face a set of problems not only because of low literacy, low socio-economic status but also because they have lack of control over their reproductive intentions and are ignorant as to how to fulfill them. Abortion is a vulnerable time for all women and is a good opportunity for intervention for the ones belonging to the lower socio-economic strata of society who have less contact with health professionals. Thus there is a need to provide fertility regulation services keeping the users perspective in mind. The current study highlights the need for population based contraception and greater awareness of the use of contraception.