Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism.

BACKGROUND/OBJECTIVES: This study aims to elucidate the genetic causes of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder resulting in GnRH deficiency, in six families from Pakistan. METHODS: Eighteen DNA samples from six families underwent genome sequencing followed by standard evaluation for pathogenic single nucleotide variants (SNVs) and small indels. All families were subsequently analyzed for pathogenic copy number variants (CNVs) using CoverageMaster. RESULTS: Novel pathogenic homozygous SNVs in known CHH genes were identified in four families: two families with variants in GNRHR, and two others harboring KISS1R variants. Subsequent investigation of CNVs in the remaining two families identified novel unique large deletions in ANOS1. CONCLUSION: A combined, systematic analysis of single nucleotide and CNVs helps to improve the diagnostic yield for variants in patients with CHH.

Massive Post-Partum Haemorrhage In A SARS-Cov-2 Positive Primi Gravid Patient: A Case Report.

A 20-year-old, primi gravid, south Asian woman, was referred from secondary care to Aga Khan University Hospital for further management of primary post-partum haemorrhage after a normal vaginal delivery, on July 12, 2021. She was otherwise healthy, with no known comorbidity. She tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during her admission, on account of universal Covid-19 testing policy. Initially, conservative measures were instituted to control bleeding, including bilateral internal iliac artery ligation, concluding with hysterectomy to stop the haemorrhage. Multiple units of blood products had to be transfused. Obstetrical haemorrhage being the menace in this case, the possibility of Covid-19 positive obstetrics patients being more susceptible to massive post-partum haemorrhage, requiring more radical life-saving procedures to be conducted earlier, was considered. In future, more observational studies will be needed to determine any association between Covid-19 infection and obstetric haemorrhage.

Acceptability of hepatitis C screening and treatment during pregnancy in pregnant women in Egypt, Pakistan, and Ukraine: A cross-sectional survey.

Chronic hepatitis C (HCV) in women of childbearing age is a major public health concern with ∼15 million women aged 15-49 years living with HCV globally in 2019. Evidence suggests HCV in pregnancy is associated with adverse pregnancy and infant outcomes. This includes ∼6% risk of infants acquiring HCV vertically, and this is the leading cause of HCV in children globally. However, few countries offer routine universal antenatal HCV screening, and direct-acting antivirals (DAAs) are not approved for pregnant or breastfeeding women although small clinical trials are ongoing. We conducted a survey of pregnant and postpartum women in 3 high HCV burden lower-middle-income countries to assess the acceptability of universal antenatal HCV screening and DAA treatment in the scenario that DAAs are approved for use in pregnancy. Pregnant and postpartum women attending antenatal clinics in Egypt, Pakistan, and Ukraine were invited to complete a survey and provide demographic and clinical data on their HCV status. Among the 630 women included (n=210 per country), 73% were pregnant and 27% postpartum, 27% were ever HCV antibody or PCR positive. Overall, 586 (93%) reported acceptability of universal antenatal HCV screening and 544 (88%) would take DAAs in pregnancy (92%, 98%, and 73% in Egypt, Pakistan, and Ukraine, respectively). Most said they would take DAAs in pregnancy to prevent vertical acquisition and other risks for the baby, and a smaller proportion would take DAAs for maternal cure. Our findings suggest that should DAAs be approved for use in pregnancy, the uptake of both HCV screening and DAA treatment may be high in women living in lower-middle-income countries.

Maternal genital tract colonisation by group-B streptococcus: a hospital based study.

OBJECTIVES: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation. METHODS: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS 11.5 was used for statistical analysis. RESULTS: The overall prevalence of colonisation was 17% (n = 69) (95% CI: 13.4-20.7). Of the 155 (38.27%) women at the Aga Khan Hospital, 35 (22.6%) were positive, while among the 250 (61.72%) women at Sobhraj Hospital, the prevalence was 13.6% (n = 34). The colonisation was found to be significantly associated inversely with the body mass index of the patient (OR 0.91; 95% CI: 0.08-1.0). CONCLUSION: Group B Streptococcus screening should be an integral part of antenatal care and should be offered to all pregnant women.

Evaluation of compliance and outcomes of a management protocol for massive postpartum hemorrhage at a tertiary care hospital in Pakistan.

BACKGROUND: Massive postpartum hemorrhage is a life threatening obstetric emergency. In order to prevent the complications associated with this condition, an organized and step-wise management protocol should be immediately initiated. METHODS: An evidence based management protocol for massive postpartum hemorrhage was implemented at Aga Khan University Hospital, Karachi, Pakistan after an audit in 2005. We sought to evaluate the compliance and outcomes associated with this management protocol 3 years after its implementation. A review of all deliveries with massive primary postpartum hemorrhage (blood loss ≥ 1500 ml) between January, 2008 to December, 2008 was carried out. Information regarding mortality, mode of delivery, possible cause of postpartum hemorrhage and medical or surgical intervention was collected. The estimation of blood loss was made via subjective and objective assessment. RESULTS: During 2008, massive postpartum hemorrhage occurred in 0.64% cases (26/4,052). No deaths were reported. The mean blood loss was 2431 ± 1817 ml (range: 1500-9000 ml). Emergency cesarean section was the most common mode of delivery (13/26; 50%) while uterine atony was the most common cause of massive postpartum hemorrhage (14/26; 54%). B-lynch suture (24%) and balloon tamponade (60%) were used more commonly as compared to our previously reported experience. Cesarean hysterectomy was performed in 3 cases (12%) for control of massive postpartum hemorrhage. More than 80% compliance was observed in 8 out of 10 steps of the management protocol. Initiation of blood transfusion at 1500 ml blood loss (89%) and overall documentation of management (92%) were favorably observed in most cases. CONCLUSION: This report details our experience with the practical implementation of a management protocol for massive postpartum hemorrhage at a tertiary care hospital in a developing country. With the exception of arterial embolization, relatively newer, simpler and potentially safer techniques are now being employed for the management of massive postpartum hemorrhage at our institution. Particular attention should be paid to the documentation of the management steps while ensuring a stricter adherence to the formulated protocols and guidelines in order to further ameliorate patient outcomes in emergency obstetrical practice. More audits like the one we performed are important to recognize and rectify any deficiencies in obstetrical practice in developing countries. Dissemination of the same is pivotal to enable an open discourse on the improvement of existing obstetrical strategies.

Is Risk Malignancy Index a Useful Tool for Predicting Malignant Ovarian Masses in Developing Countries?

Introduction. Risk of Malignancy Index (RMI) is widely studied for prediction of malignant pelvic masses in Western population. However, little is known regarding its implication in the developing countries. The objective of this study is to determine how accurately the RMI can predict the malignant pelvic masses. Materials and Methods. The study is a retrospective review of patients attending the gynecological clinic between January 2004 and December 2008 with adnexal masses. Information on demographic characteristics, ultrasound findings, menopausal status, CA125, and histopathology was collected. RMI score for each patient in the study group was calculated. Results. The study group included a total of 283 patients. Analysis of the individual parameters of RMI revealed that ultrasound was the best predictor of malignancy with a sensitivity, specificity, and positive likelihood ratio of 78.3%, 81.5%, and 4.2, respectively. At a standard cut-off value of 250, RMI had a positive likelihood ratio of 8.1, while it was 6.8 at a cut-off of 200, albeit with comparable sensitivity and specificity. Conclusion. RMI is a sensitive tool in predicting malignant adnexal masses. A cut-off of 200 may be suitable in developing countries for triaging and early referral to tertiary care centers.