左 勝則

Background: The Institute of Medicine (IOM) guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI) and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM) recommendations. Methods: We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005 e2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0-18.4, 18.5-19.9, 20-22.9, 23-24.9, and 25-27.4 kg/m(2)), we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications) using multivariate regression. Results: Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks) for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m(2), and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m(2). Conclusion: Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m(2) as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines. (C) 2017 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association.

ObjectivesTo determine the characteristics, outcomes, and prognostic factors of fetal hydrothorax (FHT) with trisomy 21. MethodsA nationwide survey was conducted on FHT fetuses with trisomy 21 delivered after 22 weeks' gestation between January 2007 and December 2011 at perinatal centers. ResultsThe 91 cases of FHT with trisomy 21 included 28 (30.8%) diagnosed in utero and 63 (69.2%) diagnosed after birth. The natural remission rate was 6.6% (6/91). Thoracoamniotic shunting was performed in 14.3% (13/91) of cases. The survival rates of the hydropic, nonhydropic, and total cases were 47.0% (31/66), 84.0% (21/25), and 57.1% (52/91), respectively. The crude odds ratio for death was 8.2 (p=0.003) for fetuses diagnosed at 26-30weeks of gestational age (vs 30weeks), 5.9 (p=0.003) for hydrops, 4.0 (p=0.04) for bilateral pleural effusion, 0.68 (p=0.42) for associated cardiovascular anomalies, and 2.1 (p=0.26) for thoracoamniotic shunting (vs no fetal therapy). ConclusionsThe prognosis of FHT with trisomy 21 was not very poor, but it was still worse than that of primary FHT. Hydrops, an early gestational age at the diagnosis and bilateral effusion, but not associated anomalies, were risk factors for death. Fetal therapy showed no survival benefit for FHT with trisomy 21. (c) 2017 John Wiley & Sons, Ltd.

Extrauterine choriocarcinoma in the fallopian tube is very rare and is often diagnosed and treated as an ectopic tubal pregnancy. A 34-year-old woman who initially became pregnant after infertility treatment using ovulation induction with clomiphene citrate and intrauterine insemination was later diagnosed with an extrauterine choriocarcinoma in the left fallopian tube. Because of suspected left ectopic tubal pregnancy based on ultrasonography findings and a high level of 13-human chorionic gonadotropin (beta-hCG; 7054.3 mIU/mL), the patient underwent diagnostic laparoscopy at a gestational age of 6 weeks. Left salpingectomy was performed based on the operative diagnosis of an ectopic tubal pregnancy. No signs of tubal rupture or leakage of contents from the fallopian tube were observed during the operation. Her serum beta-hCG dropped to 10.3 mIU/mL at 15 days postoperatively. Histopathology demonstrated an extrauterine choriocarcinoma in the removed fallopian tube, and the patient was referred to a regional oncologic hospital to receive additional adjuvant chemotherapy. This case indicates that conservative treatment for ectopic pregnancy should be chosen carefully, and that histopathology diagnosis and appropriate beta-hCG monitoring following treatment are important not only to diagnose persistent ectopic pregnancy, but also to rule out the possibility of a tubal choriocarcinoma. (C) 2017 AAGL. All rights reserved.

STUDY QUESTION: Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles. WHAT IS KNOWN ALREADY: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, the effect of letrozole on pregnancy and neonatal outcomes in FET are not well known. STUDY DESIGN SIZE, DURATION: A retrospective cohort study was conducted using data from the Japanese national ART registry between 2012 and 2013. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 110 722 single FET cycles with letrozole (n = 2409), natural (n = 41 470) or HRT cycles (n = 66 843) were included. The main outcomes were the rates of clinical pregnancy, clinical pregnancy with fetal heart beat, miscarriage and live birth. Adjusted odds ratios and relative risks (RRs) were calculated using a generalized estimating equation adjusting for correlations within clinics. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of clinical pregnancy, clinical pregnancy with fetal heart beat, and live birth were significantly higher, while the rate of miscarriage was significantly lower in the letrozole group compared with the natural and HRT groups. In blastocyst stage transfers, the adjusted RRs for clinical pregnancy with fetal heart beat of letrozole compared with natural and HRT cycles were 1.48 (95% CI: 1.41-1.55) and 1.62 (95% CI: 1.54-1.70), respectively. Similarly, the adjusted RRs of letrozole for miscarriage compared with natural and HRT cycles were 0.91 (95% CI: 0.88-0.93) and 0.84 (95% CI: 0.82-0.87), respectively. Neonatal outcomes were mostly similar in letrozole, natural and HRT cycles. LIMITATIONS REASONS FOR CAUTION: Important limitations of this study included the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that letrozole use may improve clinical pregnancy, clinical pregnancy with fetal heart beat, and live births and reduce the risk of miscarriage in patients undergoing single FET cycles.

Background: No previous study has shown the validity of a food frequency questionnaire (FFQ) in early pregnancy with consideration of nausea and vomiting during pregnancy (NVP). The aim of this study was to evaluate the validity of a FFQ in early pregnancy for Japanese pregnant women. Method: We included 188 women before 15 weeks of gestation and compared estimated nutrient intake and food group intake based on a modified FFQ with that based on 3-day dietary records (DRs). Spearman's rank correlation coefficients, adjusting energy intake and attenuating within-person error, were calculated. Subgroup analysis for those with and without NVP was conducted. We also examined the degree of appropriate classification across categories between FFQ and DRs through division of consumption of nutrients and food groups into quintiles. Results: Crude Spearman's correlation coefficients of nutrients ranged from 0.098 (sodium) to 0.401 (vitamin C), and all of the 36 nutrients were statistically significant. In 27 food groups, correlation coefficients ranged from -0.015 (alcohol) to 0.572 (yogurt), and 81% were statistically significant. In subgroup analysis, correlation coefficients in 89% of nutrients and 70% of food groups in women with NVP and 97% of nutrients and 74% of food groups in women without NVP were statistically significant. On average, 63.7% of nutrients and 60.4% of food groups were classified into same or adjacent quintiles according to the FFQ and DRs. Conclusions: The FFQ is a useful instrument, regardless of NVP, for assessing the diet of women in early pregnancy in Japan. (C) 2016 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association.

ObjectivesThis study aims to determine the prognostic factors and outcomes of primary fetal hydrothorax (FHT) and investigate the effects of fetal therapy. MethodsA nationwide survey was conducted on fetuses with primary FHT delivered after 22weeks of gestation between January 2007 and December 2011 at perinatal centers. ResultsAmong the 287 cases of primary FHT, the survival rates for those with and without hydrops were 58.0% (113/195) and 97.8% (90/92), respectively. The survival rates in the no-therapy, thoracocentesis, and thoracoamniotic shunting (TAS) groups in the hydropic cases and the non-hydropic cases were 59.7% (40/67), 51.5% (35/68), and 63.3% (38/60) and 98.1% (53/54), 96.3% (26/27), and 100% (11/11), respectively. The crude relative risk for death was 2.1 (p=0.005) for fetuses diagnosed at 26 to 30weeks of gestational age (vs 30weeks), 2.3 (p=0.001) for both skin edema and ascites, and 3.1 (p=0.02) for bilateral pleural effusion. TAS was associated with a significant risk reduction for death in hydropic cases [adjusted relative risk 0.61, p=0.01 (vs no fetal therapy)]. ConclusionsHydrops and an early gestational age at diagnosis (<30weeks of gestation), skin edema with ascites, and bilateral effusion predicted a poor prognosis in primary FHT cases. TAS was associated with a higher survival rate. (c) 2016 John Wiley & Sons, Ltd.

Background: The relative validity of food frequency questionnaires for estimating long-chain polyunsaturated fatty acid (LC-PUFA) intake among pregnant Japanese women is currently unclear. The aim of this study was to verify the external validity of a food frequency questionnaire, originally developed for non-pregnant adults, to assess the dietary intake of LC-PUFA using dietary records and serum phospholipid levels among Japanese women in early and late pregnancy. Methods: A validation study involving 188 participants in early pregnancy and 169 participants in late pregnancy was conducted. Intake LC-PUFA was estimated using a food frequency questionnaire and evaluated using a 3-day dietary record and serum phospholipid concentrations in both early and late pregnancy. Results: The food frequency questionnaire provided estimates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake with higher precision than dietary records in both early and late pregnancy. Significant correlations were observed for LC-PUFA intake estimated using dietary records in both early and late pregnancy, particularly for EPA and DHA (correlation coefficients ranged from 0.34 to 0.40, p < 0.0001). Similarly, high correlations for EPA and DHA in serum phospholipid composition were also observed in both early and late pregnancy (correlation coefficients ranged 0.27 to 0.34, p < 0.0001). Conclusions: Our findings suggest that the food frequency questionnaire, which was originally designed for non-pregnant adults and was evaluated in this study against dietary records and biological markers, has good validity for assessing LC-PUFA intake, especially EPA and DHA intake, among Japanese women in early and late pregnancy. (C) 2016 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association.

STUDY QUESTION: Does letrozole use increase the risk of major congenital anomalies and adverse pregnancy and neonatal outcomes in fresh, single-embryo transfer? SUMMARY ANSWER: Letrozole significantly decreases the risk of miscarriage and does not increase the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in patients undergoing ART. WHAT IS KNOWN ALREADY: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, its safety in terms of pregnancy and neonatal outcomes is unclear. STUDY DESIGN SIZE, DURATION: This retrospective cohort study used data from the Japanese national ART registry from 2011 to 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3136 natural cycles and 792 letrozole-induced cycles associated with fresh, single-embryo transfer and resulting in a clinical pregnancy were included in the analysis. The main pregnancy outcomes were miscarriage, ectopic pregnancy and still birth, and the neonatal outcomes were preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies. Terminated pregnancies were included in the analysis of major congenital anomalies. Odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression analysis adjusted for maternal age and calendar year. MAIN RESULTS AND THE ROLE OF CHANCE: The risk of miscarriage was significantly lower in women administered letrozole (adjusted OR [aOR], 0.37, 95% CI, 0.30-0.47, P < 0.001). There was no significant difference in the overall risk of major congenital anomalies between the two groups (natural cycle 1.5% vs letrozole 1.9%, aOR, 1.24, 95% CI, 0.64-2.40, P = 0.52), and no increased risk for any specific organ system. Subgroup analysis demonstrated that the risk of major congenital anomalies was not increased in patients who underwent either in vitro fertilization or ICSI, or in those who received early cleavage stage or blastocyst embryo transfer. All other pregnancy and neonatal outcomes were comparable between the two groups. LIMITATIONS REASONS FOR CAUTION: Despite the large sample size, we were only able to rule out the possibility that letrozole might cause large increases in birth-defect risks in ART patients. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that letrozole stimulation reduces the risk of miscarriage, with no increase in the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in women undergoing ART. Letrozole may thus be a safe option for mild ovarian stimulation.

Maternal vitamin intake during pregnancy is crucial for pregnancy outcomes and the child's subsequent health. However, there are few valid instruments for assessing vitamin intake that address the effects of nausea and vomiting during pregnancy (NVP). This study aimed to investigate the validity of a FFQ concerning vitamin intake during early and late pregnancy with and without NVP. The participants comprised 200 Japanese pregnant women who completed the FFQ and from whom blood samples were taken in early and late pregnancy. Energy-adjusted dietary vitamin intakes (vitamin C, folate, vitamin B-6, vitamin B-12, vitamin A, vitamin E and vitamin D) from FFQ were compared with their blood concentrations. A subgroup of women with NVP was investigated. In early pregnancy, significant correlations between FFQ and biomarkers were observed for vitamin C (r 0.27), folate (r 0.18) and vitamin D (r 0.26) in women with NVP and for vitamin A (r 0.18), vitamin B-12 (r 0.24) and vitamin D (r 0.23) in women without NVP. No significant correlations were observed in either group for vitamins B-6 or E. In late pregnancy, similar significant associations were observed for vitamin C (r 0.27), folate (r 0.22), vitamin B-6 (r 0.18), vitamin B-12 (r 0.27) and vitamin A (r 0.15); coefficients were higher among women without NVP. Our study demonstrates that the FFQ is a useful tool for assessing intake of several important vitamins in early and late pregnancy regardless of NVP status.

Objective To evaluate the effect of semen quality on human sex ratio in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Design Retrospective cohort study. Setting Not applicable. Patient(s) A total of 27,158 singleton infants born between 2007 and 2012 after fresh single-embryo transfer. Intervention(s) None. Main Outcome Measure(s) Proportion of male infants among liveborn infants. Result(s) There were 14,996 infants born after IVF, 12,164 infants born after ICSI with ejaculated sperm, and 646 infants born after ICSI with nonejaculated sperm. The sex ratio of IVF was 53.1% (95% confidence interval [CI], 52.3-53.9) the sex ratio of ICSI with ejaculated and nonejaculated sperm demonstrated as statistically significant reduction (48.2% 95% CI, 47.3-49.1 and 47.7% 95% CI, 43.8-51.6, respectively). In IVF, lower sperm motility, including asthenozoospermia (sperm motility &lt 40%), was associated with a statistically significantly lower sex ratio compared with normal sperm (51.0% 95% CI, 48.6-53.3 vs. 53.4% 95% CI, 52.5-54.3). In ICSI with ejaculated sperm, there was no association between sperm motility and sex ratio. Sperm concentration was not associated with sex ratio in both IVF and ICSI. Conclusion(s) In IVF, lower sperm motility was associated with a statistically significant reduction in sex ratio ICSI with either ejaculated or nonejaculated sperm was associated with a statistically significant reduction in sex ratio regardless of semen quality.

Objective To assess perinatal risk of major congenital anomalies in children born after embryo transfer with assisted hatching (AH). Design Retrospective cohort study. Setting Not applicable. Patient(s) Cycles registered from 2010 to 2012 and conceived via single-embryo transfer were included for the analysis. Live births, still births after 22 weeks of gestation, and selectively terminated cases because of congenital anomalies were included. Intervention(s) None. Main Outcome Measure(s) Major congenital anomaly. Result(s) AH was performed in 35,488 cycles among 72,125 included cycles (49.2%). A total of 1,046 major congenital anomalies (1.4%) were identified (1.36% in AH group vs. 1.50% in non-AH group). Overall risks for major congenital anomalies were not significantly different between AH and non-AH groups adjusting for maternal age, calendar year, fetal sex, embryo stage at transfer, and status of cryopreservation. There were 1,009 cases of twins (1.5%) and 10 cases of triplets (0.015%) among all included cycles. No specific organ system demonstrated significant association between AH and non-AH groups. Subgroup analysis demonstrated no significant association between AH and non-AH groups in intracytoplasmic sperm injection cycles or in vitro fertilization in fresh cycles. Similar nonsignificant association was observed between early-cleavage or blastocyst stage at transfer in frozen-thawed cycles. Conclusion(s) Our results suggest that AH alone does not increase the risk of major congenital anomaly.