Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 microg/l (0.55 to 2.55) and 1.28 microg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 microg/l (0.42 to 1.75) and 0.378 microg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 microg/l (0.18 to 0.54) and 0.199 microg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 microg/l (0.17 to 0.5) and 0.194 microg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 microg/l) as in the controls (0.1934 microg/l), this difference was not statistically significant. (p > 0.05) The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer.

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Information on the use of drugs during pregnancy is scarce and rather anecdotal. Careful consideration of the benefit to the mother and the risk to the fetus is required when prescribing drugs during pregnancy. The aim of this study was to gain knowledge on this issue in western Nepal. 2156 prescriptions of pregnant women were collected at random from the antenatal care (ANC) in obstetrics out-patient department (OPD) at Manipal Teaching Hospital (MTH), Nepal and analyzed for this study. The mean maternal age and hemoglobin concentration were 25 years and 12.21 g/dl, respectively. Twenty-three percent women attended obstetric OPD due to maternal disorders other than routine ANC (77%). Problem oriented drug use was due to nausea/vomiting (4.7%), dyspepsia (3.1%), and per vaginal spotting/bleeding (3.4%), mainly. Most of the women got 2-3 drugs and commonly included nutritional supplementation and tetanus toxoid. The average number of drugs/prescription was 2.00, 15.37% and 64.8% drugs were prescribed by generic name and as fixed dose combinations, respectively. The most commonly prescribed drugs were nutritional supplements like iron, folate, calcium, vitamins (72.8%), followed by tetanus toxoid (12.4%), gastrointestinals (5%), antimicrobials (4.6%), etc. Though, the selection of drugs was rational in most of the cases, some anomalies were observed and discussed with the clinicians. Our data reflect the general extent and prescribing pattern for those Nepalese pregnant women attending hospital in western Nepal.

BACKGROUND Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance. OBJECTIVE AND RATIONALE To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF. SEARCH METHODS Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology. OUTCOMES A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost. WIDER IMPLICATIONS This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with ‘freeze-all’ strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.

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