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Aim: This study compared the cost-effectiveness of two recombinant follicle-stimulating hormones (rFSH) formulations, Follitropin Delta and Follitropin Alfa, in controlled ovarian stimulation using cumulative live birth rates as an efficacy indicator., Methodology: This retrospective study was conducted across five clinics in Japan from April 2022 to December 2023, involving 446 first assisted reproductive technology (ART) cycles (200 with Follitropin Delta and 246 with Follitropin Alfa) were treated with rFSH monotherapy using either Follitropin Delta or Follitropin Alfa. We compared clinical outcomes such as cumulative pregnancy and live birth rates and analyzed cost-effectiveness using the cumulative live birth rates as the efficacy indicator and the incremental cost-effectiveness ratio (ICER)., Results: The Follitropin Delta group had a significantly lower incidence of ovarian hyperstimulation syndrome (15.90% vs. 27.00%, P = 0.045) and higher cumulative pregnancy rates than the Follitropin Alfa group (87.30% vs. 76.20 %; P = 0.03) after propensity score matching (PSM). Although cumulative live birth rates showed no significant differences (85.70% vs. 76.20%, P = 0.08) and Follitropin Delta demonstrated higher cost than Follitropin AlfaFollitropin Alfa (832,036 yen and 826,936 yen), ICER indicated low costs per percentage of live births (538.58 yen/%: 95% confidence interval [CI]: 275.34-12,568.69 yen)., Conclusions: Using Follitropin Delta for controlled ovarian stimulation in ART may be more cost-effective than Follitropin Alfa under Japan's Health Care Insurance System, offering higher cumulative live birth rates and minimal additional costs., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Medical Corporation Kobanawa Clinic Ethic Screening Committee issued approval 20231211. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: We would like to sincerely thank Ferring Pharmaceuticals for the generous financial support through an Investigator-Initiated Clinical Research Agreement that made this study possible. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kobanawa et al.)

Purpose: To validate the effectiveness of a gonadotropin starting dose calculator for progestin-primed ovarian stimulation (PPOS), we conducted a study comparing the outcomes of oocyte retrieval between a group assigned gonadotropin doses via the calculator and a control group, where doses were determined by the clinician's empirical judgment., Methods: Patients underwent controlled ovarian stimulation (COS) using the PPOS method, followed by oocyte retrieval. We assessed and compared the results of COS and oocyte retrieval in both groups. Additionally, we examined the concordance rate between the number of oocytes actually retrieved and the target number of oocytes in each group., Results: The calculated group demonstrated a significantly higher number of preovulation follicles and a higher ovarian sensitivity index than the control group. Furthermore, the discrepancy between the target and actual number of oocytes retrieved was notably smaller in the calculated group. The concordance rate between the target and actual number of oocytes was significantly greater in the calculated group., Conclusions: The gonadotropin starting dose calculator proved to be effective within the PPOS protocol, offering a reliable method for predicting the approximate number of oocytes to be retrieved, irrespective of the COS protocol employed., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: To create a gonadotropin starting dose calculator for controlled ovarian stimulation, which can adjust the target number of oocytes and stimulation duration for each facility to achieve individualized controlled ovarian stimulation among the Japanese patients., Methods: The patients received controlled ovarian stimulation using the gonadotropin-releasing hormone antagonist protocol, and oocytes were retrieved. Using single regression analysis, we selected age, anti-Müllerian hormone (AMH), and initial serum follicle-stimulating hormone as variables to predict the number of oocytes retrieved per gonadotropin dose (oocyte sensitivity index). Each variable was then analyzed using backward stepwise multiple regression., Results: Age and AMH were selected as predictive variables from the backward stepwise multiple regression, and we developed a multiple regression equation. We decomposed the equation as the number of oocytes retrieved/(gonadotropin starting dose × stimulation duration days) and created a calculation formula to predict the gonadotropin starting dose from the target number of oocytes and stimulation duration days., Conclusions: This is the first study to develop an individualized dosing algorithm for gonadotropins among Japanese patients. Our calculator will improve controlled ovarian stimulation performance and enable national standardization by allowing all physicians, regardless of their years of experience, to determine the appropriate starting dose of gonadotropins equally., Competing Interests: The authors declare no conflicts of interest associated with this article. All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (facilityal and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients for being included in the study. This article does not contain any studies with animal subjects performed by any of the authors. The protocol for the research project, including human subjects, has been approved by a suitably constituted Ethics Committee, ‘Medical corporation Kobanawa Clinic ethic screening committee’., (© 2023 The Author. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: The aneuploidy and sex concordance between cell-free DNA in spent culture media (SCM) and DNA from whole embryo with respect to different morphological grading were examined to evaluate the feasibility of non-invasive preimplantation genetic testing for aneuploidy (niPGT-A)., Methods: A total of 46 pairs of embryos and corresponding SCM were divided into two groups based on the morphological grade. DNA was extracted from 22 and 24 pairs of low- and high-grade embryos, respectively, and respective SCM followed by chromosomal analysis using next-generation sequencing. Aneuploidy study and sex determination were conducted for both groups, and concordance rates were calculated., Results: For low-grade embryos, 63.6% (14/22) were determined as aneuploidy by whole embryo analysis, and concordance rates were 54.5% (12/22) using niPGT-A. On the contrary, for high-grade embryos 41.7% (10/24) were determined as aneuploidy by whole embryo analysis, and concordance rates were 62.5% (15/24) using niPGT-A. The concordance rates were not statistically different between the low-grade and high-grade embryo groups ( p  = 0.804). For sex determination, concordance rates between whole embryo and SCM were 81.8% (18/22) and 87.5% (21/24) in low- and high-grade groups, respectively., Conclusion: Aneuploidy and sex evaluation by niPGT-A may be feasible for both morphologically low- and high-grade embryos., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: We focused on the metabolism of oocytes in pre-culture and insemination and compared these results between our existing fertilization medium, GEMS Fertilisation Medium (GEMS group) (Merck BioPharma) and Continuous Single Culture Medium-NX Complete (CSCM-NXC group) (FUJIFILM Irvine Scientific)., Methods: Patients under 42 years of age were received controlled ovarian stimulation and oocytes were retrieved. Those were pre-cultured and fertilized with either GEMS fertilization medium or CSCM-NXC. After fertilization was confirmed, embryos were cultured using CSCM-NXC in both groups. The embryos were cryopreserved at blastocyst stage (3BB or more, Gardner classification) and then transferred in HRT cycles., Results: The fertilization rate of both groups was the same, but the 3PN rate was significantly lower in the CSCM-NXC group. In terms of embryo culture results, the CSCM-NXC group had a significantly higher rate of good quality blastocysts, high-grade embryos, and embryos with a high degree of expansion., Conclusions: The use of CSCM-NXC, a low lactate embryo culture medium, from pre-culture and for insemination, increases the energy metabolic efficiency of oocytes and cumulus cells, making it possible to supply sufficient energy ATP for fertilization and early division, which is thought to promote good embryonic development., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes., (Copyright © 2019 Sasaki, Hamatani, Kamijo, Iwai, Kobanawa, Ogawa, Miyado and Tanaka.)