左 勝則

OBJECTIVE: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DESIGN: Retrospective, cross-sectional survey of 3103 assisted reproductive technology clinics in 74 countries in 2015 and 3249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SUBJECTS: Patients undergoing assisted reproductive technology procedures. EXPOSURE: Assisted reproductive technology. MAIN OUTCOME MEASURES: Outcomes on country, regional, and global levels. RESULTS: Reported for 2015: 2,358,239 cycles with 548,652 babies born; for 2016: 2,807,963 cycles with 647,188 babies born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 babies; in 2016, ≥3,100,448 cycles resulted in ≥723,026 babies. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous cycles were age ≥40 years. Frozen-thawed embryo transfer cycles accounted for 47.0% and 51.9%, respectively, of all embryo transfers in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all embryo transfers in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed embryo transfer was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single embryo transfers in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single embryo transfers in frozen-thawed embryo transfer autologous cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. CONCLUSION: Utilization of assisted reproductive technology and births per cycle increased from 2015 to 2016 while multiple births were reduced . Increasing proportion of frozen-thawed embryo transfer cycles, continuing wide variation in use of intracytoplasmic sperm injection, and increase in single embryo transfer rates are reported.

AIMS: This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). METHODS: A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. RESULTS: The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. CONCLUSION: In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

To assess the risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first-trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40-1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18-7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.

OBJECTIVES: To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association. METHODS: We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach. RESULTS: Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005). CONCLUSION: Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.

This study aimed to investigate assisted reproductive technology (ART) factors associated with placenta accreta spectrum (PAS) after vaginal delivery. This was a registry-based retrospective cohort study using the Japanese national ART registry. Cases of live singleton infants born via vaginal delivery after single embryo transfer (ET) between 2007 and 2020 were included (n = 224,043). PAS was diagnosed in 1412 cases (0.63% of deliveries), including 1360 cases (96.3%) derived from frozen-thawed ET cycles and 52 (3.7%) following fresh ET. Among fresh ET cycles, assisted hatching (AH) (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI] 1.4-4.7) and blastocyst embryo transfer (aOR, 2.2; 95% CI 1.3-3.9) were associated with a significantly increased risk of PAS. For frozen-thawed ET cycles, hormone replacement cycles (HRCs) constituted the greatest risk factor (aOR, 11.4; 95% CI 8.7-15.0), with PAS occurring in 1.4% of all vaginal deliveries following HRC (1258/91,418 deliveries) compared with only 0.11% following natural cycles (55/47,936). AH was also associated with a significantly increased risk of PAS in frozen-thawed cycles (aOR, 1.2; 95% CI 1.02-1.3). Our findings indicate the need for additional care in the management of patients undergoing vaginal delivery following ART with HRC and AH.