左 勝則

Abstract Aim To evaluate the impact of health insurance coverage for assisted reproductive technology (ART), introduced in Japan in April 2022, on the number of multiple embryo transfers (METs) and multiple pregnancies. Methods We analyzed Japanese ART registry data from over 600 registered ART facilities, comparing the rates and numbers of multiple pregnancies in 2022 with those in previous years. Furthermore, age‐specific MET rates and proportions of blastocyst transfers in METs were examined separately for fresh and frozen–thawed embryo transfers. Results In 2022, 3209 multiple pregnancies were reported, showing an increasing trend and a level equivalent to that in 2007, before single embryo transfer was recommended in the Japan Society for Obstetrics and Gynecology guidelines. For all embryo transfers, the MET rate was significantly lower in 2022 than in 2021, decreasing from 15.4% to 15.0% (p < 0.001), resulting in a similar rate of multiple pregnancies (2.98% vs. 3.05%; p = 0.17). Age‐specific MET rates demonstrated a similar increasing trend with age between 2021 and 2022. However, the blastocyst utilization rate in METs was significantly higher in 2022 than in 2021 across almost all age strata in frozen–thawed embryo transfers. Conclusions In 2022, the MET rate significantly decreased from 2021, whereas the multiple pregnancy rate remained similar. However, the absolute number of multiple pregnancies increased to the level before the single embryo transfer guideline, and the proportion of blastocyst transfers in MET also increased. Continuous monitoring is necessary to capture trends in the number of multiple pregnancies following ART in Japan.

Abstract STUDY QUESTION What were the rates of utilization, effectiveness, and safety for assisted reproductive technology (ART) throughout the world in 2017 and 2018, and what trends were observed? SUMMARY ANSWER The total reported number of ART fresh and frozen cycles conducted in 83 participating countries was 2 913 498 in 2017 and 3 303 505 in 2018, with 5-year trends including an increasing proportion of cycles utilizing frozen embryo transfer (FET) and an increasing number of cycles utilizing pre-implantation genetic testing (PGT). WHAT IS KNOWN ALREADY Prior reports from the International Committee Monitoring ART (ICMART) have reported on the utilization, effectiveness, and safety of ART from participating countries, with an increase in the number of cycles and number of participating countries over time. These reports have described regional differences in the utilization of ART overall, as well as differences in the utilization of specific practices such as ICSI, PGT and single embryo transfer. Past reports demonstrated that rates of delivery per cycle have increased and rates of multiple gestations have decreased over time. STUDY DESIGN, SIZE, DURATION This retrospective, cross-sectional survey describes ART procedures performed globally in 2017 and 2018. Data were submitted to ICMART by participating countries from national or regional registries. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 83 countries which provided data for cycles performed in 2017 or 2018, with the majority of countries providing data for both years. Aggregate data are reported for each participating country and analysed using methods developed by ICMART to calculate measures of utilization, effectiveness, and safety. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2 913 498 cycles and 671 012 babies born were reported for treatment performed in 2017, increasing to 3 303 505 cycles and 728 383 babies born for treatment performed in 2018. After imputing data for non-reporting centres in reporting countries, the estimated number of cycles performed in 2017 was 3 107 188 resulting in an estimated 814 588 babies. For 2018, the estimated number of cycles was 3 568 635 resulting in an estimated 870 814 babies. Utilization of ICSI for autologous fresh non-PGT cycles declined slightly compared with 2014 (54.6% in 2017 and 57.3% in 2018 compared with 64.8% in 2014). The percentage of transfers which were of frozen embryos was 55.7 % in 2017 and 57.9% in 2018, up from 38.9% in 2014. Among all countries, including those which reported no ‘freeze all’ cycles, the percentage of ‘freeze all’ cycles was 30.5% in 2017 and 32.7% in 2018, up from 13.1% in 2014. In countries reporting at least one retrieval cycle in which all embryos were frozen, the percentage of retrievals with no fresh embryo transfer increased (36.2% in 2017 and 36.8% in 2018, up from 20.1% in 2014). The number of PGT cycles in 2018 (172 247) was nearly 5-fold higher than the number reported in 2014 (36 512) with wide regional variation in utilization of PGT observed. In 2017, the delivery rate for autologous oocytes was 23.5% per oocyte retrieval, with a cumulative delivery rate of 36.4% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.8% per autologous fresh transfer, 32.5% per autologous frozen transfer, and 47.3% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 33.1% (combined fresh transfer and frozen transfers). In 2018, the delivery rate for autologous oocytes was 23.8% per oocyte retrieval, with a cumulative delivery rate of 37.3% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.3% per autologous fresh transfer, 31.9% per autologous frozen transfer, and 48.4% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 34.3%. The multiple delivery rate with autologous fresh transfer was 19.7% in 2017, and 18.3% in 2018. For autologous FET, the multiple delivery rate was 16.2% in 2017, and 14.9% in 2018. With oocyte donation (combined fresh and frozen embryo transfers), the multiple delivery rate was 15.9% in 2017, and 13.4% in 2018. Finally, the multiple delivery rate for cycles utilizing PGT was 6.9% in 2017 and 5.5% in 2018. LIMITATIONS, REASONS FOR CAUTION The data and analysis presented are dependent on the quality and completeness of the data submitted to ICMART, which varies globally. There is little data from the Middle East and some countries in Asia. It is important to note that delivery rates per transfer after PGT required the availability of embryos suitable for transfer, and therefore should not be interpreted as suggesting that PGT increases the overall success of ART per oocyte retrieval. Because of an updated methodology in the calculation of delivery rates and number of babies born, direct comparisons with past reports for these metrics cannot be made. Data are observational and it is not possible to determine the causes for regional differences in utilization, effectiveness, and safety, which are likely due at least in part to regional differences in socioeconomics, culture, resources, and regulations. WIDER IMPLICATIONS OF THE FINDINGS The ICMART report is the most comprehensive summary of global ART utilization, effectiveness and safety, currently available. There remain regional disparities in the utilization of ART, suggesting differences in access to care. These data can be used by healthcare professionals, healthcare authorities, patients, and the general public to guide research, decision-making, and policy. The reasons behind regional differences in utilization and effectiveness need to be better understood and addressed. STUDY FUNDING/COMPETING INTEREST(S) ICMART received unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also received financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. ICMART appreciates the efforts of each of the participating countries and centres which provided data. Disclosures were provided by all authors, with none indicating a conflict of interest for this manuscript. V.L.B. provides an unpaid service as a regional representative for ICMART and is a former Board member of the Executive Council of the Society for Assisted Reproductive Technology. S.D.: Ferring Pharmaceuticals provided an unrestricted grant paid to her institution in support of the African Registry and Network of ART (ANARA). Merck provided an honorarium for presentation at an educational symposium. ESHRE, the African Federation of Fertility Societies, the Egyptian Foundation of Reproductive Medicine and Embryology, the Egyptian Fertility and Sterility Society, and the Latin American Network of Assisted Reproduction provided support for conference attendance as invited speakers (travel/accommodation). S.D. is a member of Science and Technology Advisory Group, HRP WHO, and received support from the WHO to attend the annual meeting. S.D. provides unpaid services as an ICMART Board member, Director of ANARA, and an Observer on the Board of the African Federation of Fertility Societies. G.M.C.: The National Perinatal Epidemiology and Statistics Unit (NPESU) of the University of New South Wales (UNSW), Sydney was contracted by ICMART to validate the ICMART data submission and prepare the statistics tables for this report. G.M.C. is the Director of the NPESU and a UNSW employee. G.M.C. is an unpaid board member of ICMART. E.K. is an employee of the NPESU and UNSW. M.B. has received honoraria from Abbott India, Ferring, Intas Pharmaceuticals, Merk Spec, and Organon. J.d.M. has nothing to report. E.E. has no disclosures to report. F.M.B. has no disclosures to report. O.I. has received honoraria for lectures from Ferring and Organon and is an unpaid Board member of ICMART. S.C.J. is on the advisory board of Ferring. M.S.K.: Ferring and Merck have paid consultancy fees, speaker and travel support. M.S.K. participates in EIM ESHRE, German IVF registry, and ICMART. F.Z.-H.: Ferring has paid travel expenses for attending a meeting organized by Ferring. F.Z.-H. is a Latin American Network of ART Founder and honorary member, an Instituto Chileno de Medicina Reproductiva Board member, Director of the Latin American Registry of ART, and a member of Comité de ética y Políticas Publicas Sociedad Chilena de Ginecologia ny Obstetricia. G.D.A. has received travel support from ESHRE to present the ICMART annual report, as the current chair of ICMART. TRIAL REGISTRATION NUMBER n/a

Abstract Aim Assisted reproductive technology (ART) is a well‐established infertility treatment. However, financial and geographical barriers can hinder patient access. The Japanese government implemented insurance coverage in April 2022 for specific ART treatments. This study assessed the effects of insurance coverage on ART utilization and accessibility. Methods An online survey was administered to 427 ART facilities that participated in a pre‐policy assessment from December 1, 2023, to January 30, 2024. Results A total of 283 facilities responded (response rate: 66.3%). The number of ART patients increased by 4.0% (217 699–226 401) following the implementation of insurance coverage. The number of insured patients aged 25–43 years increased by 6.6%, with a notable increase of 22.9% (range: 44 144–54 253) in the 25‐ to 34‐year age group. However, the number of uninsured patients aged ≥44 decreased by 16.3%; 172 facilities experienced an increased number of patients, whereas 111 facilities experienced no increase or decline. Patient growth rates were significantly higher in rural areas than in metropolitan regions (mean difference: 0.07; 95% confidence interval: 0.0–0.1; p = 0.03). Although there was a significant negative association between the proportion of out‐of‐pocket treatment and the rate of patient increase (p = 0.02), no such association was observed in rural areas (p = 0.68). Conclusions Insurance coverage improved patient access to ART services, especially for those in their 20s and early 30s. However, the number of patients in the uninsured group decreased significantly. Accessibility in rural areas also notably improved. These findings highlight the importance of economic support for enhancing ART accessibility.

Abstract To evaluate the current perspectives on reporting success rates for assisted reproductive technology, the authors conducted a nationwide survey. Of the 327 facilities that responded (response rate: 53.5%), over half recognized potential benefits of reporting in vitro fertilization (IVF) success rates, such as aiding patients in selecting a clinic (68.5%) and enhancing the quality and efficiency of information provided to patients (62.1%). However, concerns regarding potential negative impacts, including patient selection bias, were also highlighted, albeit to a lesser extent (32.7%–52.3%). These findings underscore the need for further discussions to establish an unbiased reporting framework and improve patient education on assisted reproductive technology (ART) success rates.

Objective To identify any correlations between evidence levels, adoption rates, and additional costs of in vitro fertilization (IVF) add-ons. Design Online survey. Subjects The survey was conducted in 621 assisted reproductive technology-registered facilities that are members of the Japanese Society of Obstetrics and Gynecology from December 22, 2021, to February 13, 2022. Exposure The survey included details regarding the specific add-on modalities employed and their associated costs; inquiries pertained to the fertility healthcare infrastructure in Japan before the implementation of the National Health Insurance scheme. Main outcome measures The correlation between the adoption rate and cost of IVF add-ons and their evidence levels were analyzed. The evidence level of the add-on treatments was classified into Green, Amber, and Red categories based on the United Kingdom’s Human Fertilisation and Embryology Authority and Cochrane systematic reviews. Results A total of 438 eligible responses were analyzed, with clinics constituting 70.9% of the respondents’ facilities. A total of 18 add-ons were assessed, and 96.5% (423/438) of facilities used at least one add-on. A positive correlation of the adoption rate and an inverse correlation of the cost with the evidence level of the IVF add-on treatment were observed (not significant). Outpatient clinics, defined as medical facilities with no beds, had a significantly higher adoption rate (Amber, 65.7%; Red, 52.0%) of add-ons than other facilities, regardless of the evidence rating, although the costs were similar across all site attributes. Conclusion Accumulating evidence on the efficacy and safety of add-ons will lead to the development of medical care with a high-cost benefit, as an increase in the adoption rate and a decrease in cost are expected when limiting to medical care with a high level of evidence.

Abstract Aim To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. Methods We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first‐ and second‐line treatment protocols for CE were collected via a questionnaire. Results Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138‐positive cells for diagnosing CE was 3–5 cells/20 high‐power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first‐ and second‐line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. Conclusions There is considerable variation in the number of CD138‐positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

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.

OBJECTIVE: To evaluate assisted reproductive technology-associated risk factors for retained products of conception among live births. DESIGN: Registry-based retrospective cohort study. SETTING: Not applicable. PATIENT(S): Cycle-specific data for a total of 369,608 singleton live births after fresh and frozen-thawed embryo transfers (FETs) between 2007 and 2017 were obtained from the Japanese assisted reproductive technology registry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Retained products of conception after delivery. Odds ratios and 95% confidence intervals for risk factors associated with retained products of conception during fresh and frozen cycles. RESULT(S): In total, 132 deliveries (0.04% of eligible assisted reproductive technology registry deliveries) had retained products of conception; 122 (92.4%) of these deliveries occurred after FET transfer cycles. Cases with retained products of conception were significantly more likely to have undergone vaginal delivery than cases without retained products of conception (78.0% vs. 61.1%); they were also more likely to have been complicated with the placenta accreta spectrum (24.2% vs. 0.45%). Among patients undergoing FETs, factors associated with a significantly increased risk of retained products of conception were embryo stage at transfer, use of hormone replacement cycles, and assisted hatching. Use of hormone replacement cycles represented the largest risk factor (adjusted odds ratio, 4.9; 95% confidence interval, 2.0-12.4), such that retained products of conception occurred in 0.05% (51 of 97,958) of deliveries after hormone replacement cycles but only 0.01% (5 of 47,079) of deliveries after natural cycles. Subgroup analysis showed that hormone replacement cycles and assisted hatching remained significant risk factors for retained products of conception in cases without polycystic ovary syndrome and anovulation and cases with vaginal delivery, but not cases with cesarean section. Among fresh embryo transfers, an increased number of retrieved oocytes was the only significant risk factor for retained products of conception. CONCLUSION(S): Our analyses demonstrated that most of the cases involving retained products of conception were derived from FETs, and we identified the use of hormone replacement cycles as the largest risk factor for retained products of conception within this group.

PURPOSE: The Japan Society of Obstetrics and Gynecology (JSOG) registry gathers comprehensive data from registered assisted reproductive technology (ART) facilities in Japan. Herein, we report 2021 ART cycle characteristics and outcomes. METHODS: Descriptive statistics were used to summarize and analyze 2021 data. RESULTS: In 2021, 625 ART facilities participated in the registry; 27 facilities did not conduct ART cycles and 598 registered treatment cycles. In total, 498 140 cycles were registered, and there were 69 797 neonates (increases of 10.7% and 15.5%, respectively, from the previous year). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles decreased in 2021; the number of neonates born was 2268 for IVF-embryo transfer (ET) cycles and 2850 for ICSI cycles. Frozen-thawed ET (FET) cycles increased markedly from 2020 (11.2% increase). In 2021, 239 428 FET cycles were conducted, resulting in 87 174 pregnancies and 64 679 neonates. For fresh transfers, the total single ET, singleton pregnancy rate, and singleton live birth rates were 82.7%, 97.0%, and 97.3%; for FET, these rates were 84.9%, 96.9%, and 97.1%. CONCLUSIONS: The 2021 Japanese ART registry analysis showed marked increases in both total treatment cycles and live births from the previous year.

OBJECTIVE: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). DESIGN: A nationwide observational study. SETTING: Japan. POPULATION: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. METHODS: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. MAIN OUTCOME MEASURES: Clinical CAM. RESULTS: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63-3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20-1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57-3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58-1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. CONCLUSIONS: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation.

AIMS: In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. METHODS: ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. RESULTS: Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60-300] cycles), followed by mild ovarian simulation (60 [30-200]). Additionally, freeze-thaw embryo transfer cycles (300 [120-750]) were performed more frequently than fresh embryo transfer cycles (30 [30-60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. CONCLUSIONS: The implementation of frozen-thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

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.

This large multi-center retrospective study examined whether artificial oocyte activation (AOA) using Ca2+ ionophore following ICSI improves the live birth rate for couples with previous ICSI cycles of unexplained low fertilization rate. In this large-scale multi-center retrospective study conducted in Japan, data were collected from Keio University and 17 collaborating institutions of the Japanese Institution for Standardizing Assisted Reproductive Technology. Between January 2015 and December 2019, 198 couples were included in this study. Oocytes for both the intervention and control groups were procured from the same pool of couples. Oocytes obtained from ICSI cycles with no or low fertilization rate (<50%) with unknown causes were included in the control (conventional ICSI) group while oocytes procured from ICSI cycles followed by performing AOA were assigned to the intervention (ICSI-AOA) group. Those fertilized with surgically retrieved sperm were excluded. ICSI-AOA efficacy and safety were evaluated by comparing these two groups. Live birth rate was the primary outcome. The ICSI-AOA group (2,920 oocytes) showed a significantly higher live birth per embryo transfer rate (18.0% [57/316]) compared to that of the conventional ICSI group with no or low fertilization rate (1,973 oocytes; 4.7% [4/85]) (odds ratio 4.5, 95% confidence interval 1.6-12.6; P<0.05). A higher live birth rate was observed in younger patients without a history of oocyte retrieval. Miscarriage, preterm delivery, and fetal congenital malformation rates were similar between the two groups. ICSI-AOA may reduce fertilization failure without increasing risks during the perinatal period. AOA may be offered to couples with an ICSI fertilization rate < 50%.

To investigate the impact of a state of emergency (i.e., voluntary lockdown) during the COVID-19 epidemic, we conducted a retrospective cohort study using the Japanese nationwide registry. In comparison with those during 2019, the number of treatment cycles decreased in April 2020 (-9.5%) to its lowest point in May (-24.1%). The magnitude of the decline was three times larger for frozen cycles (-37.0%) than for fresh cycles (-12.4%). The decrease was significantly smaller for women aged <35 years (-31.0%) than for the older groups (-39.0% to -39.7%). Under voluntary lockdown, a considerable decrease was observed especially for frozen cycles and older women.

PURPOSE: To evaluate clinical outcomes after endometrial receptivity analysis (ERA). METHODS: This was a multicenter, retrospective cohort study involving 861 women who underwent ERA testing at certified fertility clinics in Japan, and who received subsequent personalized blastocyst embryo transfers (ET) between 2018 and 2020. Clinical outcomes, including pregnancies, miscarriages, and live births, were evaluated according to receptivity status for ERA. RESULTS: Mean patient age was 37.7 years (SD = 4.0), and the median number of previous ETs was 2 (interquartile range, 2-3). 41.0% (353/861) of patients were non-receptive for ERA testing. Clinical pregnancy, miscarriage, and live birth rates for personalized blastocyst ET were 44.5% (226/508), 26.1% (59/226), and 26.8% (136/508) for receptive patients, and 43.1% (152/353), 28.3% (43/152), and 28.9% (102/353) for non-receptive patients, all statistically nonsignificant. Multiple logistic regression demonstrated similar nonsignificant associations between receptivity and clinical outcomes. Greater patient age, smoking, and longer duration of infertility were significantly and negatively associated with receptivity, whereas a history of delivery was positively associated and statistically significant. CONCLUSIONS: Clinical outcomes after ERA testing were similar between receptive and non-receptive patients. Further prospective study including an appropriate comparison group are warranted to evaluate the efficacy of ERA testing.

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.

BACKGROUND: Economic disparities affect access to assisted reproductive technology (ART) treatment in many countries. At the time of this survey, Japan provided partial reimbursement for ART treatment only for those in low- or middle-income classes due to limited governmental budgets. However, the optimal level of financial support by income class remains unclear. METHODS: We conducted a conjoint analysis of ART in Japan in January 2020. We recruited 824 women with fertility problems aged 25 to 44 years via an online social research panel. They completed a questionnaire of 16 hypothetical scenarios measuring six relevant ART attributes (i.e., out-of-pocket payment, pregnancy rate, risk of adverse effects, number of visits to outpatient clinics, consultation hours and kindness of staff) and their relations to treatment choice. RESULTS: Mixed-effect logistic regression models showed that all six attributes significantly influenced treatment preferences, with participants valuing out-of-pocket payment the most, followed by pregnancy rates and kindness of staff. Significant interactions occurred between high household income (≥ 8 million JPY) and high out-of-pocket payment (≥ 500,000 JPY). However, the average marginal probability of the highest-income patients (i.e., ≥ 10 million JPY, ineligible for the subsidy) receiving ART treatment at the average cost of 400,000 JPY was 47%, compared to 56 - 61% of other income participants, who opted to receive ART at an average cost of 100,000 JPY after a 300,000 JPY subsidy. CONCLUSION: Our results suggest that out-of-pocket payment is the primary determinant in patients' decision to opt for ART treatment. High-income patients were more likely to choose treatment, even at a high cost, but their income-based ineligibility for government financial support might discourage some from receiving treatment.

BACKGROUND: This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID). METHODS: A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93). RESULTS: The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization. CONCLUSIONS: Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID.

Surgical site infection (SSI) is a common but potentially serious maternal complication of cesarean section (CS). C-reactive protein (CRP) can be used in early detection of SSI. However, its predictive value for post-cesarean SSI has never been investigated. This study aims to evaluate the predictive value of CRP for the development of SSI. This was a hospital-based retrospective cohort study of 748 pregnant women who underwent CS at our university hospital between January 2017 and December 2019. CRP was measured on postoperative days 1, 3, and 6. The predictive values of CRP for SSI were evaluated using receiver operating characteristics analysis. Forty-seven (6.3%) patients developed SSI, of whom 38 (80.9%) underwent emergency CS. Serum CRP levels were significantly higher in the SSI group than in the non-SSI group from postoperative day 1 (64 vs. 81 mg/L, p = 0.001); the difference became more evident on postoperative days 3 and 6. The area under the receiver operating characteristic curve (AUC) for CRP on days 1, 3, and 6 was 0.58 (95% confidence interval [CI], 0.49 to 0.68), 0.70 (0.62 to 0.78) and 0.73 (0.65 to 0.81), respectively. The optimal cutoff value for day 3 and 6 CRP was 66.4 mg/L (sensitivity = 76.1% and specificity = 54.4%) and 22.2 mg/L (sensitivity = 76.5% and specificity = 63.2%), respectively. CRP on postoperative days 3 and 6 can be used as a predictive marker for the development of SSI after CS. Further studies to validate the predictive value in different populations is essential.

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.