左 勝則

AIM: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. METHODS: We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. RESULTS: We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). CONCLUSIONS: Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.

PURPOSE: Since 1986, the Japan Society of Obstetrics and Gynecology assisted reproductive technology (ART) registry system has collected data on national ART use and outcomes trends in Japan. Herein, we describe the characteristics and outcomes of ART cycles registered during 2020 and compare the results with those from 2019. METHODS AND RESULTS: In 2020, 621 ART facilities participated in the registration. The total number of registered cycles was 449 900, and there were 60 381 live births, which decreased from the previous year (1.79% and 0.36% decrease, respectively). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles increased in 2020, and the number of neonates born was 2282 for IVF-embryo transfer (ET) cycles and 2596 for ICSI cycles, which had decreased from the previous year. Frozen-thawed ET (FET) cycles had slightly increased from 2019 (0.04%). In 2020, 215 285 FET cycles were conducted, resulting in 76 196 pregnancies and 55 503 neonates. Single ET was performed in 81.6% of fresh transfers and 85.1% of frozen-thawed cycles, respectively, resulting in over 97% singleton pregnancies/livebirths rates. CONCLUSION: Despite the COVID-19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated only a slight decrease in 2020 compared with 2019.

当科では主に付属器領域手術を中心に年間150例の腹腔鏡下手術を行っている。2019年1月より腹腔鏡下手術を安全に施行するための研修プログラムを策定しその効果について評価したため報告する。個人・手術室スタッフを含めたチーム・婦人科全体としての組織における腹腔鏡下手術を安全に行うための現状の問題点を挙げ対応策を検討した。医局員がドライボックスを用いた演習環境を作り、練習プログラムを作成した。実技講習会を含めたドライラボを定期的に実施し、デバイスの適正使用のためFundamental Use of Surgical Energy(FUSE)の講義内容を取り入れた安全講習会を開催した。術式の定型化をめざした手術手順書を作成し、手術室と合同勉強会を開催した。アニマルラボを実施した。同意の得られた12名の医局員を対象とし、本プログラム施行前後での腹腔鏡下手術についての知識や意識についての変化、ドライボックスでの縫合・結紮時間を調査した。本プログラム施行前後においてパワーデバイスについての特性やリスク・安全操作についての知識は有意差を持って改善した

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based assisted reproductive technology (ART) data in an online registry since 2007. Herein, we present the characteristics and treatment outcomes of ART cycles registered during 2017. Methods: We collected cycle-specific information for all ART cycles implemented at participating facilities and performed descriptive analysis. Results: In total, 448,210 treatment cycles and 56,617 neonates (1 in 16.7 neonates born in Japan) were reported in 2017, increased from 2016; the number of initiated fresh cycles decreased for the first time ever. The mean patient age was 38.0 years (standard deviation 4.6). A total 110,641 of 245,205 egg retrieval cycles (45.1%) were freeze-all cycles; fresh embryo transfer (ET) was performed in 55,720 cycles. A total 194,415 frozen-thawed ET cycles were reported, resulting in 66,881 pregnancies and 47,807 neonates born. Single ET (SET) was performed in 81.8% of fresh transfers and 83.4% of frozen cycles, with singleton pregnancy/live birth rates of 97.5%/97.3% and 96.7%/96.6%, respectively. Conclusions: Total ART cycles and subsequent live births increased continuously in 2017, whereas the number of initiated fresh cycles decreased. SET was performed in over 80% of cases, and ET shifted from using fresh embryos to frozen ones.

＜文献概要＞●レトロゾールは多嚢胞性卵巣症候群に対する排卵誘発薬として,従来用いられてきたクロミフェンよりも高い排卵誘発成功率,生産率が報告されている.●日本における多嚢胞性卵巣症候群に対する排卵誘発の第一選択薬はクロミフェンであるが,諸外国のガイドラインでは近年レトロゾールを第一選択として推奨するものが存在する.●排卵誘発薬としてレトロゾールを使用する際は,適応外使用であるため,患者個々に説明を行い,書面による同意を得るのが望ましい.

病理学的に良悪性を診断できない平滑筋腫瘍は、STUMP(Smooth muscle tumors of uncertain malignant potential)と定義される。STUMPの正確な頻度は不明であるが、非常に稀な疾患であると報告されている。しかし再発や転移例もあり、その管理に注意を要する。今回我々は、卵管から発生したSTUMPを経験したので報告する。症例は70歳、2妊2産で、黄色帯下を主訴に前医を受診した。経腟超音波検査で左付属器領域に5cm大の充実性腫瘤を認めたため、当科紹介受診した。MRI、CTなどの精査の結果、充実性左卵巣腫瘍の術前診断となり、腹式両側付属器切除術の方針とした。実際に開腹すると左卵巣は正常大であり、左卵管峡部から左卵巣と連続した6cm大の腫瘍を認めた。両側付属器切除を施行し、残存病変なく手術終了した。術後経過良好のため術後7日目に退院した。摘出した腫瘍は、病理学的検索の結果STUMPと診断された。そのため術後再度全身精査を行ったが、明らかな残存病変や転移の所見はなく、現在外来で経過観察中である。卵管平滑筋腫瘍は術前に診断することが困難であり、今回の症例のように平滑筋腫瘍であっても必ずしも良性でないことがあるため注意を要する。(著者抄録)

BACKGROUND/OBJECTIVES: Vegetable intake during childhood may reduce the risk of subsequent asthma. We verified the effect of maternal intake during pregnancy on asthma risk in offspring, which has rarely been studied. SUBJECTS/METHODS: In a hospital-based birth cohort study conducted in Tokyo, we administered a food frequency questionnaire at two periods during the respondents' pregnancy: early and mid to late periods. In addition, a questionnaire including the International Study of Asthma and Allergies in Childhood questionnaire was conducted when the offspring were 2 years old. Multivariate Poisson regression adjusting for maternal baseline demographics was used to elucidate the association between maternal vegetable intake and the incidence of wheeze in the offspring. RESULTS: Among 310 singletons, 82 (26.5%) experienced wheeze at 2 years of age. Women with the highest intake of cruciferous, and folate-rich vegetables during early pregnancy reported a significantly lower prevalence of wheeze in their child at 2 years of age in comparison with those who reported the lowest intake (adjusted risk ratio: 0.48 and 0.47, 95% confidence interval: 0.26-0.89, and 0.25-0.87, respectively). In trend analysis, a higher maternal intake of cruciferous, folate-rich vegetables, and total vegetables during early pregnancy was less likely to be associated with wheeze in the offspring at 2 years old (p for trend: 0.038, <0.001, and 0.028, respectively). Maternal vegetable intake during mid to late pregnancy was not associated with wheeze in the offspring. CONCLUSIONS: Maternal vegetable intake during early pregnancy may have a protective effect against asthma in offspring at 2 years of age.

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 (&lt;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 &lt; 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 &lt; 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 &lt; 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.