Assisted reproductive technology in Japan: A summary report for 2020 by the ethics Committee of the Japan Society of obstetrics and gynecology

Abstract 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.


| INTRODUC TI ON
Japanese women remain among the most significant users of assisted reproductive technology (ART) globally, 1 and in 2019, 2 the number of treatment cycles (458 101 treatment cycles) and neonates (60598) resulting from ART increased from that reported in 2018. 3 Despite Japan having the highest utilization rate of ART, Japan's total fertility rate has progressively decreased over the past four decades. 4 In 2019, the total fertility rate in Japan was 1.36, reaching a record low as reported by the Ministry of Health, Labour and Welfare, compared with 1.44 reported in 2016 1 and 2.4 reported globally by the World Bank. 5 The total fertility rate in 2020 remained low at 1.33 (fixed), and in 2021, it decreased further to 1.30 (based on monthly annual report calculations). 6 Along with the decreasing trend of the total fertility rate and the number of neonates born in Japan, the proportion of neonates born from ART has been increasing.
Since 1986, the ART registry system of the Japan Society of Obstetrics and Gynecology (JSOG), and the online registration system implemented in 2007, have been collecting data on national trends of ART use and outcomes to understand the current effectiveness of ART, ensure ART safety, and inform decision-making related to ART in Japan. 2 The present report aims to summarize the data on characteristics and outcomes of registered ART cycles during 2020 and to compare the present results with results from previous years.

| Data source and data collection
The JSOG registry requested ART facilities across Japan to register data on the demographic and background characteristics of patients, clinical information including infertility diagnosis, pregnancy history, and delivery outcomes, and ART-cycle specific data since 2007. 6 The present descriptive analysis investigated registered cycle characteristics and treatment outcomes using data from the Japanese ART registry in 2020, with a cutoff date of 30 November 2021.

| Variables of interest
Data for the following variables by fertilization method (in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], and frozen-thawed embryo transfer [FET]) were collected, analyzed, and compared with data from previous years: Numbers of registered cycles, oocyte retrievals, embryo transfer (ET) cycles, freeze-allembryo/oocyte cycle, pregnancies, and neonates. Characteristics of registered cycles and pregnancy outcomes were described for fresh, FET, and embryo transfers using frozen-thawed oocyte cycles. Fresh cycle data were stratified by fertilization method (i.e., IVF, ICSI, and gamete intrafallopian transfer (GIFT)).

| Outcomes
The treatment outcomes analyzed and compared were as follows: pregnancy, defined as confirmation of a gestational sac in utero; miscarriage, defined as spontaneous or unplanned loss of a fetus from the uterus before 22 weeks of gestation; live birth, defined as delivery of at least one live neonate after 22 weeks of gestation; and multiple pregnancy rates. The pregnancy outcomes analyzed and compared were as follows: ectopic pregnancy, heterotopic pregnancy, artificially induced abortion, stillbirth, and fetal reduction. The following outcomes were also analyzed by maternal age: pregnancy, live birth, miscarriage, and multiple pregnancy rates.
Treatment outcomes for FET cycles using frozen-thawed oocytes were also analyzed.

| Statistical analysis
All analyses were conducted using the STATA MP statistical package, version 17.0 (Stata, College Station). Since the study focuses on descriptive analysis, statistical testing was not conducted.

| RE SULTS
The number of ART facilities participating in the registry in 2020 was 621 out of a total of 622 registered ART facilities in Japan. Among the 621 facilities participating in the registration, 20 did not implement any ART treatment. Including split-ICSI cycles.
c Including cycles using frozen-thawed oocyte.

| Treatment and pregnancy outcomes
The detailed characteristics and treatment outcomes of registered fresh cycles are shown in Of these, 757 cycles led to successfully frozen oocytes.  Table 4 shows the treatment outcomes of registered cycles by maternal age in 2020. Figure 2 shows the pregnancy, live birth, and miscarriage rates by maternal age in all registered cycles in 2020.

| DISCUSS ION
In this report, we describe the characteristics and outcomes of ART cycles registered in the Japanese ART registry system during 2020 and compare the present results with those from 2019 2 and previous years. 3 In 2020, the JSOG registered a total of 449 900 ART cycles in Japan, which resulted in the birth of 60 381 neonates. contact unless necessary to address essential or urgent matters. 20,21 Because of such restrictions, ART procedures, which may have been deemed non-essential or non-urgent, were expected to decrease in 2020.
The In 2021 Tsutsumi et al. reported that at Sanno Hospital, the number of ETs was temporarily decreased, but the number of oocyte retrievals increased. However, many patients wished to continue ART treatments while taking appropriate measures to prevent COVID-19 infection and any potential sequelae to the mother and neonate. 28 Similar concerns and desires were voiced by patients in other countries who also experienced cancellations or delays in ART cycles. 25,26 After the first statement issued by the JSRM to patients, a web questionnaire survey conducted in August 2020 by a non-profit organization in support of patients with infertility issues revealed that many patients were concerned about COVID-19.
Many wanted to continue ART treatments, especially those aged >40 years, and a large number of patients asserted that infertility treatments are not "non-essential and non-urgent" matters, which posed an important ethical dilemma at the time. 29  be collected, as these may have a significant impact on ART outcomes. These data will be included in the registries from January 2022. Because the data collection for the registry was carried out per cycle, we could not distinguish whether a person received multiple treatment cycles.
To conclude, the 2020 analysis of the ART registry showed that despite the COVID-19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated a slight decrease in 2020 compared with 2019, while the number of FETs maintained an increasing trend in 2020 (a small increase of 0.04% from 2019). The rate of single ETs, both fresh and frozen, also increased in 2020, but the increase was slightly higher for FET cycles. For both fresh and FET cycles, the rates of singleton pregnancies and live births were over 97%, similar to those in 2019. The ART use and outcomes trends in Japan in 2020 were similar to those of the previous year. It will be interesting to compare these results with future results after the recent implementation of the Japanese government health coverage for ART.
F I G U R E 2 Pregnancy, live birth, and miscarriage rates according to patient age in all registered cycles in 2019. Adapted from the Japan Society of Obstetrics and Gynecology ART Databook 2020 (https:// www.jsog.or.jp/activ ity/art/2020d ata_202208.pdf). ET, embryo transfer TA B L E 5 Treatment outcomes of embryo transfers using frozenthawed oocyte in assisted reproductive technology in Japan, 2020