Hiromitsu Shirasawa

Aim: To investigate whether the etiology of diminished ovarian reserve (DOR) independently influences outcomes of assisted reproductive technology (ART). Methods: This multicenter, retrospective cohort study was a secondary analysis of a nationwide cohort established by the Reproductive Endocrinology Committee of the Japanese Society of Obstetrics and Gynecology. Women with DOR (anti‐Müllerian hormone [AMH] levels < 1.1 ng/mL) who initiated their first in vitro fertilization and/or intracytoplasmic sperm injection cycle between January and December 2021 were included in the study. The causes of DOR were classified as idiopathic, previous anticancer treatment, ovarian surgery for endometriosis, or ovarian surgery for ovarian tumors other than endometriosis. Multivariate logistic regression analyses were performed to identify factors associated with ongoing pregnancy and live births. Results: Overall, 606 women were included in this study. Baseline AMH levels differed among DOR etiologies and were the lowest in women with previous anticancer treatment. In multivariate analyses, age, number of oocytes retrieved, and number of good‐quality embryos were independently associated with ongoing pregnancy and live birth, whereas the etiology of DOR was not. The cumulative ongoing pregnancy and live birth rates per embryo transfer cycle did not differ significantly among DOR etiologies. Conclusion: In this cohort, treatment outcomes were more strongly associated with age and embryo‐related factors than with the underlying etiology of DOR. However, because the number of women with previous anticancer treatment was limited, further studies are needed to clarify the impact of chemotherapy‐related DOR.

Aim: To evaluate how diagnostic methods, criteria, and treatment for chronic endometritis (CE) changed in Japan after introducing health insurance coverage of assisted reproductive technology (ART). Methods: We conducted two nationwide, web‐based facility surveys targeting all 616 registered ART facilities. The surveys were administered before ART insurance coverage (December 2021 to February 2022) and after coverage (December 2023 to January 2024). Facilities that responded to both surveys (283 facilities) were included. We evaluated whether facility‐level CE diagnostic methods, CD138‐positive plasma cell cutoff values, and first‐ and second‐line treatment choices changed between surveys. Results: CE testing was implemented by 238 facilities in the precoverage and 244 postcoverage periods. The adoption of diagnostic methods did not significantly change. Although the overall number of facilities that adopted CD138 immunohistochemical staining was stable (145 vs. 149 facilities), 23 facilities discontinued CD138 staining postcoverage while 27 newly introduced it; discontinuation occurred predominantly in clinics (91.3%), whereas 44% of new adopters were hospitals/university hospitals ( p < 0.001). The cutoff value of CD138‐positive cells (6–10 cells/20 high‐power fields) increased between the surveys ( p = 0.01). Doxycycline remained the first‐line therapy. Regarding second‐line therapy, ciprofloxacin plus metronidazole remained the most frequent, while probiotics significantly increased ( p = 0.005). Conclusions: After ART insurance coverage in Japan, overall CE diagnostic methods and CD138 adoption remained largely unchanged. However, facilities tended to adopt higher CD138 cutoff values and treatment selections shifted. Establishing unified diagnostic criteria and treatment protocols is warranted to support standardized CE care for future health insurance coverage.

Background: Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and has been associated with impaired fertility; however, its effects on ovarian reserve and infertility treatment outcomes remain controversial. Methods: A narrative review was performed using PubMed to identify clinical and experimental studies addressing TAI, ovarian reserve, premature ovarian insufficiency (POI), and infertility treatment outcomes. Results: Clinical evidence suggests that TAI is associated with modestly reduced AMH levels in adult women, although the magnitude of this decline appears insufficient to indicate imminent POI. In contrast, adolescents with TAI may exhibit elevated AMH. Observational studies describe a frequent coexistence of TAI and POI; however, Mendelian randomization analyses suggest that POI may predispose to TAI rather than the reverse. Mechanistic studies show that thyroid hormones act directly on ovarian cells via thyroid hormone receptors, while immune‐mediated pathways involving cytokines, oxidative stress, and anti‐ovarian antibodies may contribute to follicular dysfunction. Evidence regarding assisted reproductive technology outcomes in euthyroid TAI remains inconsistent. Conclusion: TAI may exert a subtle influence on ovarian reserve through complex endocrine and immune mechanisms, with age‐specific variation. Although AMH alterations are observed, their clinical relevance for fertility and treatment outcomes remains unclear, highlighting the need for longitudinal studies.

Aim: To examine the cumulative ongoing pregnancy/live birth rate per patient by encompassing all embryo transfer (ET) cycles associated with a single oocyte retrieval cycle among women with diminished ovarian reserve (DOR), and to investigate whether serum anti‐Müllerian hormone (AMH) levels can predict a live birth success.Methods: This multi‐institutional retrospective cohort study included infertile women with DOR (AMH <1.1 ng/mL) who began their first cycle of in vitro fertilization and/or intracytoplasmic sperm injection between January and December 2021. Outcomes using the retrieved embryos were evaluated for up to four ET cycles.Results: Of 606 patients, 113 did not undergo ET. A total of 605 ET cycles were analyzed. Clinical pregnancy and ongoing pregnancy/live birth rates per ET cycle were significantly dependent on age, not AMH levels. Ongoing pregnancy/live birth rates per patient increased significantly with higher AMH levels. A significant difference in the cumulative ongoing pregnancy/live birth rate was observed depending on whether cases with no remaining embryos were included among the censored cases.Conclusion: Assisted reproductive technology (ART) outcomes per ET cycle in women with DOR were similar to those reported in the Japanese ART registry without distinguishing DOR. The greater the number of good‐quality embryos that can be frozen, the higher the expected cumulative live birth rate.

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.

Aim: How has the treatment policy changed since the introduction of health insurance coverage for assisted reproductive technology (ART) in Japan?Methods: This study was conducted as a nationwide fact‐finding survey to determine the current situation of ART treatment in Japan, the IZANAMI project. Among the 616 ART facilities across Japan, 283 (45.9%) that responded to the first (December 2021–February 2022) and second surveys (December 2023–January 2024) were recruited. Information on the clinical practices was collected via a questionnaire survey and analyzed.Results: Among the facilities with ≤200, 201–500, 501–1000, 1001–2000, and ≥2000 annual oocyte retrieval (OR) cycles, 93.9%, 88.7%, 75.0%, 69.7% and 42.9% performed ≥80% of their OR cycles using health insurance, respectively (p < 0.001), whereas 51.9%, 53.7%, 41.0%, 40.0% and 12.5% exhibited an increase in number of OR cycles, respectively (p = 0.03). Therefore, a significantly higher proportion of smaller‐scale institutions than larger clinics had insured treatment and an increase in the number of OR cycles. Significantly more large clinics than small facilities selected mild stimulation, intracytoplasmic sperm injection, and freeze‐all embryo cycle; however, no significant transitions were observed in the main policies for ART, regardless of facility size. However, the indication for mild stimulation significantly increased in normal to high responders, and the choice of ovarian stimulation protocol according to the patient's wishes was significantly reduced.Conclusions: Small‐scale institutions were more likely to offer insured treatment and increase the number of OR cycles than large facilities; however, the main protocols did not significantly change.

Background: Embryologists are crucial in assisted reproductive technology (ART), yet their duties, education, and licensing requirements vary significantly across countries, complicating the determination of optimal staffing levels in ART laboratories. With anticipated advancements such as automation in ART laboratories, this review comprehensively analyzes factors necessary for appropriate future staffing. Main Findings: A comprehensive literature search was conducted using PubMed to identify relevant articles up to July 2024, employing keywords such as “embryologist,” “staffing,” and “certification.” Articles were evaluated for content related to laboratory operations, and guidelines from five organizations regarding licensing and education were compared. Results: The review revealed significant international differences in embryologist certification, duties, and staffing recommendations. These disparities, along with the integration of advanced ART technologies and regulatory requirements, significantly impact future staffing needs in ART laboratories. Conclusion: The definitions of an ART cycle and required staffing levels vary across organizations, influenced by the certification and duties of embryologists in different countries. Adequate embryologist staffing is essential for ensuring laboratory quality control and impacting patient ART outcomes. As new technologies and automation reshape laboratory workflows, collaborative efforts among organizations, countries, and embryologist associations are essential for developing comprehensive educational curricula and determining appropriate staffing levels.

Aim: We aimed to assess the amniotic fluid glucose concentration cut‐off as an indicator of fetal chromosomal abnormalities, such as trisomy 13, 18, and 21.Methods: This prospective observational study included pregnant females who underwent amniocentesis. Participants were divided into two groups on the border of 22 weeks of gestational age (p = 0.002 in the p = 0.039 in the ≥22 week group). According to receiver operating characteristic curves, the optimal cut‐off point of glucose concentration was 46 mg/dL in the <22 week group (odds ratio 6.55; 95% confidence interval 1.78–24.1) and 24 mg/dL in the ≥22 week group (odds ratio 8.40; 95% confidence interval 1.83–38.6).Conclusions: Our study suggested that glucose concentration in amniotic fluid is an indicator of trisomy 13, 18, and 21. Amniotic fluid glucose concentration itself does not diagnose fetal trisomy, but this may be helpful in selecting treatment facilities.

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.

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.