Assisted reproductive technology in Japan: A summary report for 2017 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology

Abstract 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.

TA B L E 1 Trends in the number of registered initiated cycles, egg retrievals, pregnancies, and neonates according to IVF, ICSI, and frozen-thawed ET cycles in Japan, 1985 Treatment outcomes included pregnancy, miscarriage and live birth rates, multiple pregnancies, pregnancy outcomes for ectopic pregnancy, intrauterine pregnancy coexisting with an ectopic pregnancy, artificial abortion, stillbirth, and fetal reduction. Furthermore, the treatment outcomes of pregnancy, live birth, miscarriage, and multiple pregnancy rates were analyzed according to patient age. We also described treatment outcomes for cycles using frozen-thawed oocytes based on medical indications.  The characteristics and treatment outcomes of registered fresh cycles are shown in Table 2  a significantly higher live birth rate than did fresh blastocyst ET (RR = 1.26, 95% CI, 1.14 to 1.41). 6 Thus, evidence for the use of a freeze-all strategy in the entire IVF population remains limited.

| D ISCUSS I ON
FET might increase specific complications during pregnancy.
Previous analysis using the Japanese ART registry has demonstrated that FET is associated with significantly higher risk for hypertensive disorders of pregnancy (HDP) and placenta accreta than fresh ET. 7 In particular, higher risk of HDP in FET is noted in several RCTs. 4,6 Recently, it was reported that methods of endometrium preparation, especially hormone replacement cycles for FET, might be associated with these complications. 8  Society for Reproductive Medicine and the Society for Assisted Reproductive Technology have concluded that routine use of ICSI in patients with non-male factor infertility is not recommended. 13 The strength of the Japanese ART registry is its mandatory reporting system with a high compliance rate, in cooperation with the government subsidy system. Using this system, nearly all participating ART facilities (606 of 607 facilities) have registered cycle-specific information.
Nevertheless, several limitations exist in the registry. First, the registry includes only cycle-specific information; it is very difficult to identify cycles in the same patient using the registry. Under current Japanese ART practice, in which nearly half of initiated cycles are freeze-all, current indicators such as pregnancy and live birth rate per aspiration cycle would be markedly underestimated. In fact, the abovementioned report from ICMART described that the delivery rate per oocyte aspiration in Japan was the lowest among 65 countries, which could mislead public opinion regarding the quality of treatment as ET was not performed in most included fresh cycles. 1 It has recently been suggested that the cumulative live birth rate per oocyte aspiration is more suitable when reporting the success rate of IVF outcomes. 14,15 Yet, the appropriate definitions to be used in calculating the cumulative live birth rate are under discussion. The format of the Japanese ART registry may need to be changed, to report indicators for comparability.
Second, the Japanese ART registry includes unfertilized oocyte freezing cycles only for medically indicated cases, such as fertility preservation in cancer patients; the registry does not include cycles with non-medical indications. Because no other regulatory measure in reproductive medicine that includes oocyte freezing is enforced in Japan, there is no information available regarding the practices outside this registry.
In conclusion, our analysis of the ART registry during 2017 demonstrated that the total number of ART cycles increased whereas the number of initiated fresh cycles decreased for the first time ever. SET was performed at a rate of more than 80%, resulting in a 97% singleton live birth rate. Although an increasing trend for frozen ET and freeze-all cycles is characteristic in Japan, further investigation is required to evaluate the effect of the freeze-all strategy and frozen ET on cumulative live births, and particularly with respect to both maternal and neonatal safety issues. These data represent the latest clinical practices of ART in Japan. Further improvement in the ART registration system in Japan is important.

ACK N OWLED G M ENTS
We thank all of the registered facilities for their cooperation in providing their responses. We would also like to encourage these facilities to continue promoting use of the online registry system and assisting us with our research. This study was supported by Health and Labour Sciences Research Grants. We thank Analisa Avila, ELS, of Edanz Group (www.edanz editi ng.com/ac) for editing a draft of this manuscript.

CO N FLI C T O F I NTE R E S T
There is no conflict of interest regarding the publication of this study.

H U M A N R I G HT S S TATE M E NT A N D I N FO R M E D CO N S E NT
All procedures were performed in accordance with the ethical standards of the relevant committees on human experimentation (institutional and national) and the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients included the study.

A N I M A L R I G HTS
This report does not contain any studies performed by any of the authors that included animal participants.

A PPROVA L BY E TH I C S CO M M IT TE E
Not applicable.