The objective of this paper is to study the possible additive effect of corticosteroids to the known effect of indomethacin on potency of the human ductus arteriosus. Systolic and diastolic blood flow of the fetal ductus arteriosus was measured by echo Doppler at 26-32 weeks of gestation. Four groups of patients were studied according to the treatment they have received: group A (exposure to indomethacin and betamethasone); group B (indomethacin alone); group C (betamethasone); and group D (controls). Children in whom ductal constriction was noted in utero were followed by repeat cardiac echo Doppler examinations at the age of 1 to 2 years. In group A (indomethacin and betamethasone) fetal ductal constriction was significantly higher (p = 0.02) and occurred in 11 out of 15 fetuses (73.3%), compared with 5 out of 14 (37.2%) of the fetuses in group B (indomethacin alone). In group C (betamethasone) and D fetuses (no treatment), no significant ductal constriction was observed. Pathological tricuspid regurgitation and right ventricular dilation were found more frequently in fetuses from group A. No long-term sequella was noted in the infants in whom ductal constriction had been noted in utero. Corticosteroids and indomethacin have a synergistic effect on the frequency and severity of fetal ductus arteriosus constriction. In short-term treatment this effect is transient, and has no deleterious effects on fetal and neonatal cardiac function.
Abstract Endometrial dating (ED) is the process by which the menstrual cycle day is estimated and is an important tool for the evaluation of uterine status. To date, ED methods remain inaccurate and controversial. We demonstrate how the rise of computerized virtual histology changes the state of affairs and introduce a new ED method. We present the results of a clinical trial where magnified images of ex-vivo endometrial tissue samples were captured at different cycle days, together with measurements of serum hormone levels on the same day. Patient testimonies about their cycle day were also collected. Computerized image analysis, followed by statistical representation of the tissue features, allowed mathematical representation of the cycle day. The samples underwent ED histological assessment, which is currently the ED gold standard. We compared dating results from patient reports, serum hormone levels, and histology to establish their concordance level. We then compared histology-based ED with the new method ED in the secretory phase (i.e. post ovulation). The correlation coefficient between the two resulted in an R = 0.89 with a P-value of P < 10 –4 . The new method, Virtual Pathology Endometrial Dating (VPED), has the benefit of being a real time, in-vivo method that can be repeatedly applied without tissue damage, using a dedicated hysteroscope. One practical use of this method may be the determination of accurate real-time embryo transfer timing in IVF treatments.
Abstract STUDY QUESTION Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? SUMMARY ANSWER The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes. WHAT IS KNOWN ALREADY There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently. STUDY DESIGN, SIZE, DURATION A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome. MAIN RESULTS AND THE ROLE OF CHANCE Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11–1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04–1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27–1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86–1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97–1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions. LIMITATIONS, REASONS FOR CAUTION There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate. WIDER IMPLICATIONS OF THE FINDINGS There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies. STUDY FUNDING/COMPETING INTEREST(S) No financial assistance was received. The authors have no competing interests. REGISTRATION NUMBER N/A.
