OBJECTIVE To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study. METHODS Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997–2009 births in a population-based case–control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing. RESULTS Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective β-blockers, centrally acting agents, renin–angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective β-blockers (adjusted OR 3.22, 95% CI 1.47–7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76–2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41–6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective β-blocker use, and late initiation of treatment, respectively. CONCLUSION Our study suggests a relationship between hypospadias and the severity of hypertension.

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OBJECTIVE: The aim of this study was to evaluate the efficacy of melatonin and/or resveratrol administration on embryo development and clinical outcomes in poor-prognosis IVF patients.DESIGN: This study was a retrospective observational study conducted at Kyono ART clinic in Japan from October 2010 to November 2017. MATERIALS AND METHODS: A total of 372 patients who failed to conceive in a previous ART cycle due to poor embryo development were included and divided into three groups: a melatonin administration group (MLT group), a resveratrol group (RSV group), and a melatonin and resveratrol administration group (MLT/RSV group). The numbers of cycles were 296, 35, and 116 in the MLT group, RSV group, and MLT/RSV group, respectively. We designated the previous ART cycle of each patient in the three groups as control. Primary endpoints were fertilization rate and embryo quality. Secondary endpoints were pregnancy rate and miscarriage rate. Characteristics of each group and their control are shown in Table. Fisher's exact test and Mann-Whitney U tests were used for statistical analysis.RESULTS: In the MLT group, fertilization rate (72.5% vs. 63.5%: p<0.01), blastocyst formation rate (45.7% vs.31.0%: p<0.01), and good-blastocyst rate (8.7% vs.20.4%: p<0.01) were significantly higher than control. In the RSV group, although fertilization rate (66.7% vs. 52.8%: p¼0.07) and good-blastocyst rate (25.6% vs. 8.0%: p¼0.08) were higher than control, the results did not reach statistical significance. In the MLT/RSV group, blastocyst formation rate (49.5% vs. 31.6%: p<0.01) and good-blastocyst rate (23.6% vs.13.6%: p<0.01) were significantly higher than control. The MLT group showed significantly higher pregnancy rate (22.0% vs.9.6%: p<0.01) and lower miscarriage rate (30.6% vs.60.6%: p<0.01) than control. The RSV group showed no significant difference in pregnancy rate and miscarriage rate. The MLT/RSV group showed significantly higher pregnancy rate (20.8% vs.6.6%: p<0.05) and lower miscarriage rate (27.3% vs.75%: p<0.01) than control. There was no side effect of melatonin and resveratrol administration.CONCLUSIONS: Our findings have shown that melatonin administration to poor-prognosis IVF patients during controlled ovarian stimulation in their ART cycle could improve embryo development and clinical outcomes. In consideration of the beneficial effect of resveratrol on SIRT1 activation, co-administration of resveratrol with melatonin might be more favorable.Characteristics of patients in each group and their control.