The IVF-LUBE trial - a randomized trial to assess Lipiodol® uterine bathing effect in women with endometriosis or repeat implantation failure undergoing IVF.

RESEARCH QUESTION: Does pre-IVF Lipiodol® increase the success of IVF treatment in women with endometriosis or repeat implantation failure (RIF) compared with IVF alone? DESIGN: Lipiodol is known to enhance natural fertility, especially amongst women with endometriosis. The effect of Lipiodol may accrue through an impact on the endometrium that enhances receptivity to implantation. A randomized controlled trial (RCT) was carried out on 70 women due to undergo IVF. Women with endometriosis or RIF in previous IVF treatments, recruited from IVF clinics in New Zealand and in Pune, India, received either Lipiodol by hysterosalpingogram or no intervention prior to IVF treatment. RESULTS: Between May 2009 and January 2014, 33 women were randomized to Lipiodol plus IVF and 37 to IVF alone. When pregnancies resulting from fresh embryo transfer from the IVF cycle under study were considered, live birth rates were 8/33 (24%) in the pre-IVF Lipiodol group and 11/37 (30%) in the IVF only group (relative risk [RR] 0.81; 95% confidence interval [CI] 0.37 to 1.8). Live birth rates from pregnancies within 6 months were 11/33 (33%) and 12/37 (32%) in these respective groups (RR 1.03; 95% CI, 0.53 to 2.0). The trial was underpowered to detect smaller differences between treatment and control groups. CONCLUSIONS: No evidence was found of benefit of Lipiodol prior to fresh embryo transfer in women with endometriosis or RIF. It is suggested that this treatment should not be undertaken purely as an adjuvant in IVF other than in the context of a further well-designed RCT.

Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial.

STUDY QUESTION: Is oral dydrogesterone 30 mg daily non-inferior to 8% micronized vaginal progesterone (MVP) gel 90 mg daily for luteal phase support in IVF? SUMMARY ANSWER: Oral dydrogesterone demonstrated non-inferiority to MVP gel for the presence of fetal heartbeats at 12 weeks of gestation (non-inferiority margin 10%). WHAT IS KNOWN ALREADY: The standard of care for luteal phase support in IVF is the use of MVP; however, it is associated with vaginal irritation, discharge and poor patient compliance. Oral dydrogesterone may replace MVP as the standard of care if it is found to be efficacious with an acceptable safety profile. STUDY DESIGN, SIZE, DURATION: Lotus II was a randomized, open-label, multicenter, Phase III, non-inferiority study conducted at 37 IVF centers in 10 countries worldwide, from August 2015 until May 2017. In total, 1034 premenopausal women (>18 to <42 years of age) undergoing IVF were randomized 1:1 (stratified by country and age group), using an Interactive Web Response System, to receive oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects received either oral dydrogesterone (n = 520) or MVP gel (n = 514) on the day of oocyte retrieval, and luteal phase support continued until 12 weeks of gestation. The primary outcome measure was the presence of fetal heartbeats at 12 weeks of gestation, as determined by transvaginal ultrasound. MAIN RESULTS AND THE ROLE OF CHANCE: Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates in the full analysis sample (FAS) at 12 weeks of gestation of 38.7% (191/494) and 35.0% (171/489) in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). Live birth rates in the FAS of 34.4% (170/494) and 32.5% (159/489) were obtained for the oral dydrogesterone and MVP gel groups, respectively (adjusted difference 1.9%; 95% CI: -4.0 to 7.8). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP gel. LIMITATIONS, REASONS FOR CAUTION: The analysis of the results was powered to consider the ongoing pregnancy rate, but a primary objective of greater clinical interest may have been the live birth rate. This study was open-label as it was not technically feasible to make a placebo applicator for MVP gel, which may have increased the risk of bias for the subjective endpoints reported in this study. While the use of oral dydrogesterone in fresh-cycle IVF was investigated in this study, further research is needed to investigate its efficacy in programmed frozen-thawed cycles where corpora lutea do not exist. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that oral dydrogesterone is a viable alternative to MVP gel, due to its comparable efficacy and tolerability profiles. Owing to its patient-friendly oral administration route, dydrogesterone may replace MVP as the standard of care for luteal phase support in fresh-cycle IVF. STUDY FUNDING/COMPETING INTERESTS(S): This study was sponsored and supported by Abbott. G.G. has received investigator fees from Abbott during the conduct of the study. Outside of this submitted work, G.G. has received non-financial support from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope and Gedeon Richter, as well as personal fees from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope, VitroLife, NMC Healthcare, ReprodWissen, Biosilu, Gedeon Richter and ZIVA. C.B. is the President of the Belgian Society of Reproductive Medicine (unpaid) and Section Editor of Reproductive BioMedicine Online. C.B. has received grants from Ferring Pharmaceuticals, participated in an MSD sponsored trial, and has received payment from Ferring, MSD, Biomérieux, Abbott and Merck for lectures. G.S. has no conflicts of interest to be declared. A.P. is the General Secretary of the Indian Society of Assisted Reproduction (2017-2018). B.D. is President of Pune Obstetric and Gynecological Society (2017-2018). D.-Z.Y. has no conflicts of interest to be declared. Z.-J.C. has no conflicts of interest to be declared. E.K. is an employee of Abbott Laboratories GmbH, Hannover, Germany and owns shares in Abbott. C.P.-F. is an employee of Abbott GmbH & Co. KG, Wiesbaden, Germany and owns shares in Abbott. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Origio, Besins, Ferring and Mithra (now Allergan); and H.T. has received consultancy fees from Finox-Gedeon Richter, Merck, Ferring, Abbott and ObsEva. TRIAL REGISTRATION NUMBER: NCT02491437 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 08 July 2015. DATE OF FIRST PATIENT'S ENROLLMENT: 17 August 2015.

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients.

Indian College of Physicians Position Statement: Addictive Disorders Among Persons with Diabetes Mellitus.

OBJECTIVES: Migraine, a common primary headache disorder which can be severely disabling, associated with poor health-related quality of life (HRQoL) amongst affected patients. The present study was performed to provide adequate clinical data on migraine and the management practices in India. MATERIAL AND METHODS: A cross-sectional study was designed to assess disease burden, HRQoL, symptom profile, management trends and comorbidities associated with migraine patients across ten centres in India. This study assessed HRQoL using Migraine Specific Quality of life (MSQ) and Migraine Disability Assessment Scores (MIDAS) questionnaire. Categorical variables were summarized as frequency, and percentage and continuous variables as mean and standard deviation respectively. RESULTS: A total of 705 patients were enrolled with a mean age of 35.2 years. Hypertension (7.0%) was the highest co-morbid illness associated with migraine. A higher MSQ score was observed in females as compared to males (39.3±12.4 and 37.4±11.6) while MIDAS showed a comparable score (27.7±47.6 and 27.2±35.4). Majority of migraine patients were unemployed (61.6%) and in profession, females had poor HRQoL than males by MIDAS and MSQ. Majority of patients had pulsating, bilateral attacks for the duration of 4h to 72 h. Paracetamol (47.1%) and propranolol (50.9%) was most commonly prescribed drugs for acute attack and prophylaxis, respectively. CONCLUSION: The quality of life was superior in males as compared to females amongst migraine patients in India. Hypertension was the commonest comorbidity associated with migraine. KEY MESSAGES: Migraine is associated with substantial disability with higher prevalence in females and older people (age >40 years). NSAIDs and propanol was widely prescribed drug in acute attacks and prophylaxis of migraine respectively. Cardiovascular diseases, diabetes mellitus and anxiety were common comorbidities associated with migraine.

Oxidative stress-mediated essential polyunsaturated fatty acid alterations in female infertility.

Prostaglandins are exclusively synthesized in vivo from cell membrane essential fatty acids and together are known to regulate many aspects of reproductive processes. The objective of the study was to examine whether disturbances in fatty acid profile as a result of increased oxidative stress could be one of the causes of female infertility. Forty-five infertile and 30 control women were enrolled via the Department of Obstetrics and Gynecology of Bharati Medical College Hospital, Pune, India. Essential polyunsaturated fatty acids, malondialdehyde (MDA; oxidative stress-marker) levels and antioxidants (vitamins E and C) were measured in both groups. Results show that plasma eicosapentaenoic acid and erythrocyte docosahexaenoic acid levels were reduced (p < 0.05) in infertile women as compared to controls. Likewise, levels of MDA, a peroxidative product of essential fatty acids, were increased (p < 0.05) and vitamin E concentrations were decreased (p < 0.05) in infertile women, suggesting that increased oxidative stress and consequent altered essential polyunsaturated fatty acids are associated with infertility. Our study indicates, for the first time, the cause and effect relationship between oxidative stress and membrane essential polyunsaturated fatty acids in infertile women. These data have important implications for the supplementation of a combination of omega-3 fatty acids and antioxidants in the successful management of female infertility.

Diabetes and Anemia: International Diabetes Federation (IDF) - Southeast Asian Region (SEAR) position statement.

Anemia is often associated with diabetes mellitus and is known to intensify the risk of developing diabetes-related microvascular and macrovascular complications. There is paucity in understanding of co-existence of these conditions, especially in Southeast Asian countries. Iron and/or erythropoietin deficiencies are the major causes of anemia in diabetes, and diabetic kidney disease plays a key role. Patients with diabetes need to be screened for anemia along with other risk factors and anemia should be corrected appropriately to improve overall clinical outcomes. This position statement aims to provide a comprehensive overview and an algorithm for appropriate management of anemia in patients with diabetes.

Rare case of primary mucinous adenocarcinoma of vagina.

Here we present a rare case of primary mucinous adenocarcinoma of vagina treated successfully with wide local excision and post-operative radiotherapy. There was no recurrence even after four years.