Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome: A systematic review with meta-analyses.

BACKGROUND: Polycystic ovary syndrome (PCOS) has a prevalence of 8%-13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines. METHODS: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta-analyses were conducted, where appropriate. RESULTS: Fifty-six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low-quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] -4.02 [-5.23, -2.81], P < 0.001); COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], P < 0.00001). In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI. CONCLUSIONS: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m2 . There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin.

Dose-response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man.

BACKGROUND: CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release. METHODS: Healthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model. RESULTS: ED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance. CONCLUSIONS: In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.

Preclinical Pharmacology of CW002: A Nondepolarizing Neuromuscular Blocking Drug of Intermediate Duration, Degraded and Antagonized by l-cysteine-Additional Studies of Safety and Efficacy in the Anesthetized Rhesus Monkey and Cat.

BACKGROUND: CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by L-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous L-cysteine. Further, Institutional Animal Care and Use Committee-approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described. METHODS: Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by L-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated. RESULTS: ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; L-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and >>0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95. CONCLUSIONS: The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by L-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.

Recommendations on routine mid-trimester anomaly scan.

The purpose of this paper is to discuss the minimal requirements of the routine mid-trimester anomaly scan in Asian countries after taking into account various factors, including local circumstances, medical practice, guidelines, and availability of experienced sonographers and high-resolution ultrasound machines, which affect the prenatal detection rate of fetal anomalies. In general, a routine mid-trimester anomaly scan includes the assessment of the number of fetuses, fetal cardiac activity, size, anatomy, liquor and placental location. The most controversial issue is which fetal structures should at least be examined. We discussed the requirements of a basic routine scan, as well as the optional views, which can be obtained if feasible to improve the detection of fetal, placental or maternal abnormalities. Routine anomaly scan remains a clinical challenge.

Best Practice Recommendations for Infertility Management.

Aim: The objective of this document is to provide guidance to the infertility specialist, gynecologist, embryologist, and counselors on the management of sub-fertility and brief them with the recent advances in the field. These recommendations will aid the aforementioned healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients with the best available evidence. Participants: Extensive deliberations, discussion, and brainstorming was done between different reproductive medicine (RM) specialists, to develop the recommendations. Evidence: A systematic review of the literature published up to June 2019 was carried out using PubMed and Cochrane Collaboration Library. International guidelines, cohort studies, case series, observational studies, and randomized controlled trials currently available in the literature were reviewed. Indian data whatever available was also reviewed. Process: Primary meetings were held with leading reproductive medicine specialists. Each topic was brainstormed on by a group of reproductive medicine experts, who then prepared the first draft of the recommendation. These recommendations then were reviewed by Dr. Jaideep Malhotra, Dr. Gouri Devi, and Dr. Madhuri Patil along with the chief co-ordinator of each consensus to finalize the final draft. Conclusions: From the literature and discussion of the available evidence, several topics were identified for which evidence is inconsistent, insufficient, or non-existing. For the benefit of couples undergoing several treatments, the working committee recommends that future research, where possible in well-designed RCTs, will help in establishing evidence for a particular practice. In the Indian context, one also needs to take into consideration facilities and options available, cost, lack of insurance coverage, experimental nature of some advanced techniques used.

The challenges of obesity for fertility: A FIGO literature review.

Obesity has been linked to infertility through several mechanisms, including at a molecular level. Those living with obesity face additional barriers to accessing fertility treatments and achieving a successful pregnancy, which can contribute to their economic and psychosocial stressors. There is scope to further improve care for people living with obesity and infertility with empathy, via a multidisciplinary approach.

FIGO statement: Fertility preservation.

Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.

Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung lobectomy.

Lone atrial fibrillation (AF) is associated with various ion channel gene sequence variants, notably the common S38G loss-of-function polymorphism in the KCNE1 K(+) channel ancillary subunit gene. New-onset postoperative AF (POAF) generally occurs 48-72 h after major surgery, particularly following procedures within the chest, but its molecular bases remain poorly understood. To begin to address this gap in knowledge, we analyzed molecular changes in the left atrium (LA) in relation to simultaneous changes in hemodynamics, LA effective refractory period (ERP), and the capacity to sustain electrically-induced AF following left upper lung lobectomy in swine. Relative to control pigs (no previous surgery), 3 days after lobectomy higher values for mean pulmonary artery pressure (16 ± 1 vs 22 ± 2 mmHg; P=0.045) and pulmonary vascular resistance (273 ± 47 vs 481 ± 63 dyns/cm(5); P=0.025) were evident, whereas other hemodynamic variables were unchanged. LA ERP trended toward reduction in lobectomy animals (187 ± 16 vs 170 ± 20 ms, P>0.05). None of the lobectomy pigs developed spontaneous POAF as assessed by telemetric ECG. However, all lobectomy pigs, but none of the controls, were able to sustain AF induced by a 10s burst of rapid pacing for ≥ 30 s (P=0.0079), independent of LA ERP; AF was sustained ≥ 60s in 3/5 postoperative pigs versus 0/5 controls and correlated with a shorter ERP overall (P=0.023). Transcriptomic analysis of LA tissue revealed 23 up-regulated and 10 down-regulated transcripts (≥ 1.5-fold, P<0.05) in lobectomy pigs. Strikingly, of the latter, KCNE1 down-regulation showed the statistically strongest link to surgery (2.0-fold, P=0.009), recapitulated at the protein level with Western blotting (P=0.039), suggesting KCNE1 down-regulation as a possible common mechanistic factor in POAF and lone AF. Of the up-regulated transcripts, while Teneurin-2 was the strongest linked (1.5-fold change, P=0.001), DSCR5 showed the highest induction (2.7-fold, P=0.02); this and other hits will be targeted in future functional studies.

Effect of Reproductive and Lifestyle Factors on Anti-Mullerian Hormone Levels in Women of Indian Origin.

Background: Infertility is a world-wide problem and one third females. Over the years, anti-mullerian hormone (AMH) has emerged as a major marker of ovarian reserve. There is also increasing interest in determining the factors which can impact AMH levels. Aims: To correlate the association of reproductive and lifestyle factors on AMH levels in women of Indian origin. Settings and Design: Multicentric cross sectional study. Materials and Methods: The study was conducted using data extracted from the patient records of seven private fertility practices located in North India. Women who were attending these clinics for fertility treatment were requested to fill the questionnaire related to reproductive and lifestyle factors. Statistical Analysis used: Our outcome variable was level of AMH measured in the past 3 months, and was assessed as normal or low. All analyses were conducted using STATA 17. Results: We found a direct association of low AMH with increasing age, short cycles, amenorrhea and women with family history of premature menopause. We found a direct correlation of high AMH and women with polycystic ovary syndrome and those whose partners had Oligoasthenoteratozoospermia (OATS) or azoospermia. There was no correlation with smoking, sleep, diet, body mass index, cell phone or laptop use in our study. Conclusion: Reproductive and lifestyle factors may affect ovarian reserve and but there was a dearth of human studies in this area. To the best of our knowledge this is the first human study on the effect of AMH on Laptop and Cell phone use. We urgently need more studies to confirm or refute our findings so that we can counsel our patients well.

Indian Society for Assisted Reproduction Consensus Guidelines on Preimplantation Genetic Testing in In vitro Fertilization Clinics.

STUDY QUESTION: What are the good practice guidelines for Pre implantation genetic testing applicable in INDIA? WHAT IS ALREADY KNOWN: Pre-Implantation Genetic Testing (PGT) is not new in India. It is used to identify euploid embryos for transfer, thus enabling couples to achieve a healthy pregnancy. There has been a lot of controversy surrounding PGT in the international forums; most of these debates have failed to reach a consensus on whether PGT should be offered or its concerns be validated more. STUDY DESIGN SIZE DURATION: This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on Pre implantation genetic testing and embryo biopsy practices in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. PARTICIPANTS/MATERIALS SETTING METHODS: Expert professionals from ISAR representing clinical, embryological and genetic fields. MAIN RESULTS AND THE ROLE OF CHANCE: The report is divided into various components defining the terminologies, the various requirements, qualifications, recommendations on PGT -A,M,SR, and quality management: the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. LIMITATIONS REASONS FOR CAUTION: The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines can help labs across the country to standardise their PGT services and improve clinical outcomes. STUDY FUNDING/COMPETING INTERESTS: The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.

ISAR Consensus Guidelines on Add-Ons Treatment in In vitro Fertilization.

STUDY QUESTION: What are the good practices for the use of ADD-ON Treatments in IVF cycles in INDIA? WHAT IS ALREADY KNOWN: Add on treatments in IVF are procedures and technologies which are offered to patients in hope of improving the success rates. A lot of add on treatments exist; most of them have limited evidence and data for the Indian patient population is miniscule. These interventions may have limited effects, so it is imperative that any new technology that is offered is evaluated properly and has enough evidence to suggest that it is safe and effective. STUDY DESIGN SIZE DURATION: This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on Add on treatments in IVF in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. PARTICIPANTS/MATERIALS SETTING METHODS: Expert professionals from ISAR representing clinical and embryology fields. MAIN RESULTS AND THE ROLE OF CHANCE: The report is divided in various components including the health of the Offspring, the various ADD ons available to an ART center, consensus points for each technology & qualifications and trainings for embryologists, the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. LIMITATIONS REASONS FOR CAUTION: The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines can help labs across the country to standardise their ART services and improve clinical outcomes, it will also motivate clinics to collect data and report the use of Add ons to the national registry. STUDY FUNDING/COMPETING INTERESTS: The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.

ISAR Consensus Guidelines on Safety and Ethical Practices in In vitro Fertilization Clinics.

STUDY QUESTION: What are the Safe and Ethical practices for ART applicable in INDIA? WHAT IS ALREADY KNOWN: The Indian IVF industry is booming; with mushrooming of assisted reproductive technology (ART) clinics in the country, the need for regulation is immense. The ISAR has taken up this initiative to lead the way forward in establishing practice guidelines for the safe and ethical use of ARTs in our country. These guidelines discuss the points to consider before the starting of an IVF unit, to the designing of the laboratory, the staffing pattern and experience recommendations, laboratory safety guidelines, documentation and patient traceability, gamete traceability, handling biological material, the consumables and media, and different consents and checklists and also propose key performance indicators for the Indian scenario. STUDY DESIGN SIZE DURATION: This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on safe and ethical ivf practices in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. PARTICIPANTS/MATERIALS SETTING METHODS: Expert professionals from ISAR representing clinical and embryology fields. MAIN RESULTS AND THE ROLE OF CHANCE: The report is divided in various components including the regulations, the various requirements for an ART center, qualifications and trainings, recommendations on good practices and quality management: the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. LIMITATIONS REASONS FOR CAUTION: The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines can help labs across the country to standardise their ART services and improve clinical outcomes. STUDY FUNDING/COMPETING INTERESTS: The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.

Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.

The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.

Cysteine reversal of the novel neuromuscular blocking drug CW002 in dogs: pharmacodynamics, acute cardiovascular effects, and preliminary toxicology.

BACKGROUND: CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. METHODS: Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. RESULTS: L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. CONCLUSION: The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

Pharmacodynamics and cardiopulmonary side effects of CW002, a cysteine-reversible neuromuscular blocking drug in dogs.

BACKGROUND: CW002 is a novel neuromuscular blocking drug with a duration dependent on the rate of cysteine adduction to the molecule. The current study characterized the pharmacodynamics and cardiopulmonary side effects of CW002 in dogs. METHODS: In eight beagles, the dose required to produce 95% neuromuscular blockade (ED95) for CW002 was first determined and cysteine reversibility was confirmed. Five to 7 days later, incrementally larger doses were injected starting with 6.25 x ED95 and doubling the dose every 15 min. Before and after injection, blood was obtained for histamine analysis. Systemic and pulmonary arterial pressures, cardiac output, and left ventricular pressure and volume were recorded along with inspiratory pressure and pulmonary compliance. Ventricular contractility and lusitropy were indexed from pressure and volume data. RESULTS: The ED95 for CW002 from pooled data was 0.009 mg/kg. At 3 x ED95, onset time was 2.6 +/- 0.9 min and duration was 47 +/- 9 min. The duration was shortened to 3.7 +/- 0.6 min by 50 mg/kg L-cysteine injected 1 min after CW002. At 25 x ED95, CW002 reduced mean arterial pressure with concomitant decreases in systemic vascular resistance, mean pulmonary artery pressure, cardiac output, contractility, and lusitropy, beginning at 50 x ED95. However, even at a dose of 100 x ED95, the average change in any variable was less than 20%. There were no changes in pulmonary vascular resistance or ventilation mechanics at any dose, and histamine release occurred in only two of eight animals. CONCLUSIONS: CW002 is a potent neuromuscular blocking drug that at doses up to 100 x ED95 produces modest hemodynamic effects that are not associated with bronchoconstriction or consistent histamine release.

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners.

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre-eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under- and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women's health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system-wide public health approach to influence the wider determinants as well as individual factors influencing preconception health.

Indian National Association for the Study of the Liver-Federation of Obstetric and Gynaecological Societies of India Position Statement on Management of Liver Diseases in Pregnancy.

Liver diseases occurring during pregnancy can be serious and can progress rapidly, affecting outcomes for both the mother and fetus. They are a common cause of concern to an obstetrician and an important reason for referral to a hepatologist, gastroenterologist, or physician. Liver diseases during pregnancy can be divided into disorders unique to pregnancy, those coincidental with pregnancy, and preexisting liver diseases exacerbated by pregnancy. A rapid differential diagnosis between liver diseases related or unrelated to pregnancy is required so that specialist and urgent management of these conditions can be carried out. Specific Indian guidelines for the management of these patients are lacking. The Indian National Association for the Study of the Liver (INASL) in association with the Federation of Obstetric and Gynaecological Societies of India (FOGSI) had set up a taskforce for development of consensus guidelines for management of patients with liver diseases during pregnancy, relevant to India. For development of these guidelines, a two-day roundtable meeting was held on 26-27 May 2018 in New Delhi, to discuss, debate, and finalize the consensus statements. Only those statements that were unanimously approved by most members of the taskforce were accepted. The primary objective of this review is to present the consensus statements approved jointly by the INASL and FOGSI for diagnosing and managing pregnant women with liver diseases. This article provides an overview of liver diseases occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and the recommended treatment options.

Open-label, Prospective, Investigator Initiated Study to Assess the Clinical Role of Oral Natural or Synthetic Progesterone During Stimulated IUI Cycles for Unexplained Infertility.

BACKGROUND: Unexplained infertility remains as one of the important subtype of infertility that follows expectant management with Intrauterine Insemination (IUI) in most cases. AIM: To evaluate the clinical role of progesterone supplement as luteal phase support for women with unexplained infertility following stimulation protocol with Clomiphene Citrate (CC)/Human Menopausal Gonadotropin (HMG). MATERIALS AND METHODS: An investigator initiated study to survey the success rate for first cycle of IUI following stimulation protocol with CC/HMG & luteal phase support with oral natural or synthetic progesterone was conducted. 120 patient records between observation period of Jan to May '14 were retrieved especially for subjects undergoing IUI procedure for Unexplained infertility. Patients with baseline Serum (Sr). progesterone records who received Oral Natural Micronized Progesterone Sustained Release (Oral NMP SR) (N=45) or Dydrogesterone (n=33) following CC/HMG induction protocol and human Chorionic Gonadotropin(HCG) Inj., were further analysed following Luteal Phase Support(LPS) with oral natural or synthetic progesterone. RESULTS: Baseline demographics showed 78 patients with mean age, weight and cycle duration of 29.5 yrs, 57.3 kg & 28.6 days respectively. Progesterone was supplemented as Oral NMP SR 200/300 mg OD or Dydrogesterone 10 mg bid in 22, 23 and 33 patients respectively. In all cases ovulation was triggered with HCG inj., followed by IUI within the next 48 hours while baseline sr. progesterone levels were being assessed. Medicines and Healthcare Products Regulatory Agency (MHRA) UK recommended therapeutic compliance to suggest sr. progesterone levels of ≥14ng/ml were recorded as Mid-luteal levels in all of these patients. This therapeutic compliance was noted in 82.2% & 78.8% of the patients treated with oral NMP SR or Dydrogesterone respectively. Pregnancy was observed amongst 5 and 10 patients treated with oral NMP SR and Dydrogesterone respectively at the end of 'First' IUI cycle. Both the groups were well tolerated with drowsiness documented in three cases for Oral NMP SR. CONCLUSION: Clinical supplementation with ONMPSR suggests therapeutic compliance and alternative strategy to conventional formulations while offering dosing convenience with minimal side effects.