Ovulation induction using clomiphene citrate using stair – Step regimen versus traditional regimen in polycystic ovary syndrome women – A randomized control trial

Objective: To determine the efficacy of the stair-step protocol (SSP) using clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS) and compare it with traditional regimen. Design: This was randomized control trial. Setting: Infertility Clinic. Patient(s): Sixty infertile PCOS women. Intervention(s): Patients were randomized into the study (SSP – 30 patients) and control group (traditional protocol – 30 patients). In the SSP, patients were treated with CC 50 mg/day for 5 days and in nonresponsive patients, the dosage was increased to 100 mg/day for 5 days in the same cycle. Maximum dose of 150 mg was given until the dominant follicle was generated. In control group, the dose increment in nonovulatory cases was done in subsequent cycle. Ultrasonography follow-up was done to detect ovulation. Main Outcome Measure(s): Ovulation rate and duration of treatment. Results: Ovulation (66.7% vs. 50% respectively) and pregnancy rates (26.7% vs. 15.7%) were similar between the stair step and the control group. The duration of treatment was significantly shorter in stair step compared to traditional protocol (17.23 vs. 53 days). CC 100 mg was the most effective dose for ovulation in either group. There were no significant differences in the systemic side effect. Conclusions: By using SSP, effective treatment is provided in significantly shorter time period without any detrimental effect on the ovulation and pregnancy rates

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer

Background & objectives: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. Methods: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. Results: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment. Interpretation & conclusions: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response

Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women

Non-alcoholic fatty liver disease (NAFLD) is a frequent occurrence in polycystic ovarian syndrome (PCOS). We studied the frequencies and characteristics of NAFLD in PCOS women. We compared various methods of detection of advanced fibrosis/cirrhosis. One hundred and forty women with PCOS and seventy controls, matched for age, were evaluated for the presence of NAFLD. Anthropometric variables, serum levels of aminotransferases, glucose, lipids and transient elastography were done. Thirty-six percent of the NAFLD patients had abnormal aminotransferases. In women presenting to an infertility clinic, NAFLD was higher in both obese and non-obese PCOS women, being present in 117 (83.6%) of PCOS cases and 32 (45.7%) of non-PCOS controls (p< .001). Fibroscan is helpful in evaluating for liver fibrosis in patients with NAFLD.Impact Statement What is already known on this subject? Polycystic ovarian syndrome (PCOS) has been associated with many long-term health complications including endometrial cancer, diabetes, hypertension and metabolic syndrome. The association of PCOS with NAFLD has been suggested. NAFLD is recognised as a leading cause of liver dysfunction which can progress to long-term sequel of cirrhosis. What do the results of this study add? In this study, asymptomatic women seeking treatment of infertility were screened for presence of NAFLD. The study shows a high prevalence of NAFLD in young Indian women. The prevalence was significantly higher in women with PCOS than non-PCOS women. What are the implications of these findings for clinical practice and/or further research? The findings of the study suggest that all infertile women, especially those with PCOS, should be screened for NAFLD. This will help in early identification and management of this condition and to avoid long-term consequences of liver dysfunction and cirrhosis. PCOS is an independent risk factor for the development of NAFLD in obese women. Liver ultrasound, serum levels of transaminases clinch the diagnosis. Short of liver biopsy, non-invasive tests like Fibroscan and NAFLD fibrosis score are useful to assess the stage of fibrosis

Stillbirths: Progress and unfinished business

This first paper of the Lancet Series on ending preventable stillbirths reviews progress in essential areas, identified in the 2011 call to action for stillbirth prevention, to inform the integrated post-2015 agenda for maternal and newborn health. Worldwide attention to babies who die in stillbirth is rapidly increasing, from integration within the new Global Strategy for Women's, Children's and Adolescents' Health, to country policies inspired by the Every Newborn Action Plan. Supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging. Prenatal health is a crucial biological foundation to life-long health. A key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health. Still, specific actions for stillbirths are needed for advocacy, policy formulation, monitoring, and research, including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival. Strong leadership is needed worldwide and in countries. Institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies

Stillbirths : progress and unfinished business

This first paper of the Lancet Series on ending preventable stillbirths reviews progress in essential areas, identified in the 2011 call to action for stillbirth prevention, to inform the integrated post-2015 agenda for maternal and newborn health. Worldwide attention to babies who die in stillbirth is rapidly increasing, from integration within the new Global Strategy for Women's, Children's and Adolescents' Health, to country policies inspired by the Every Newborn Action Plan. Supportive new guidance and metrics including stillbirth as a core health indicator and measure of quality of care are emerging. Prenatal health is a crucial biological foundation to life-long health. A key priority is to integrate action for prenatal health within the continuum of care for maternal and newborn health. Still, specific actions for stillbirths are needed for advocacy, policy formulation, monitoring, and research, including improvement in the dearth of data for effective coverage of proven interventions for prenatal survival. Strong leadership is needed worldwide and in countries. Institutions with a mandate to lead global efforts for mothers and their babies must assert their leadership to reduce stillbirths by promoting healthy and safe pregnancies