Verification of the utility of the gonadotropin starting dose calculator in progestin-primed ovarian stimulation: A comparison of empirical and calculated controlled ovarian stimulation.

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.

The gonadotropins starting dose calculator, which can be adjusted the target number of oocytes and stimulation duration days to achieve individualized controlled ovarian stimulation in Japanese patients.

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.

Aneuploidy and sex concordance rate between cell-free DNA analysis from spent culture media of preimplantation embryo and DNA from whole embryo with respect to different morphological grading.

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.

Fertilization, embryo culture, and clinical results using low lactate embryo culture medium for pre-culture, insemination, and beyond.

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.

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence.

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.