BackgroundInfertility remains a major global public health issue, affecting an estimated 17.5% of couples of reproductive age in their lifetime. Fertility rates in ASEAN countries have declined below replacement thresholds, highlighting the urgent need to enhance assisted reproductive technology (ART) strategies. Controlled ovarian stimulation is central to optimising ART outcomes, yet guidance tailored to ASEAN population is limited.MethodsA comprehensive literature review (January 2015 to April 2025) informed the development of thirty statements, referencing the European Society of Human Reproduction and Embryology (ESHRE) Guideline on Ovarian Stimulation for in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) 2025. A modified Delphi methodology and GRADE-ADOLOPMENT framework were employed to ensure evidence-based, context-sensitive recommendations. Statements deemed irrelevant to this consensus discussion were excluded. Consensus was defined as ≥70% expert agreement.ResultsOf 30 draft statements, consensus was achieved on 28 final statements after three Delphi rounds. Gonadotrophin-releasing hormone (GnRH) antagonist protocols were considered safe and preferred in predicted normal and high responders with comparable efficacy. In freeze-all cycles, progestin protocol was considered probably equivalent to GnRH analogues for pituitary suppression. Recombinant follicle-stimulating hormone (rFSH) and highly-purified human menopausal gonadotrophin (HP-hMG) were equally recommended; however, in predicted high responders, HP-hMG was noted to potentially reduce the risk of ovarian hyperstimulation syndrome (OHSS). Mixed stimulation protocols combining rFSH and HP-hMG from the start of stimulation are favoured over mid-follicular phase combinations for predicted normal and low responders. Follitropin delta and alpha/beta were considered probably equivalent, with algorithm-guided follitropin delta preferred when OHSS risk is a concern. Adjunctive letrozole or clomiphene was generally not recommended. Mid-cycle dose adjustments may be used pragmatically to reduce the risk of cycle cancellation or OHSS, and recombinant luteinising hormone (rLH) supplementation may benefit selected subgroups (e.g., advanced age or low responders), although evidence remains heterogeneous.ConclusionThis consensus provides evidence-informed ovarian stimulation strategies tailored to different patient profiles, emphasising safety, efficacy, and personalisation to optimise IVF/ICSI outcomes. Where evidence is limited, statements reflect expert consensus and should be applied as conditional guidance. It balances global best practices with regional realities to support effective, safer, and personalised ART in ASEAN.
IntroductionMale infertility affects nearly half of infertile couples and is increasingly recognized as a marker of overall male health rather than a condition limited to reproductive function. Despite growing evidence supporting early andrological assessment, preventive male reproductive healthcare remains underutilized. This study evaluated the reasons for accessing semen analysis, the prevalence of seminal abnormalities at first evaluation, and the clinical factors associated with impaired semen quality in a contemporary Italian cohort.MethodsWe conducted a single-center cross-sectional observational study including 930 consecutive men undergoing semen analysis at a tertiary fertility center between November 2023 and January 2024. Participants completed a structured questionnaire collecting demographic, clinical, reproductive, and lifestyle information. Semen analyses were performed according to the WHO 2021 Laboratory Manual. Patients were initially classified according to the indication for semen analysis (preventive screening, clinical follow-up, or fertility assessment), and subsequently according to previous semen analysis and previous andrological evaluation. Multivariable logistic regression was used to identify independent predictors of WHO-defined seminal abnormalities.ResultsThe median age was 37.5 years (IQR 33.8–41.4). Fertility assessment represented the primary indication for semen analysis (88.7%), whereas only 3.4% of men underwent testing for preventive purposes. Overall, 32.2% of participants were undergoing their first semen analysis, and among these, 76.3% had never received an andrological evaluation. Men typically accessed reproductive health services only in their late thirties. At first semen analysis, abnormalities were frequently detected, including impaired total progressive motility (61%), abnormal morphology (70%), reduced sperm concentration (25%), and reduced total motility (32%). Multivariable analysis identified varicocele as the strongest and most consistent independent predictor of seminal abnormalities across multiple parameters, whereas age and body mass index showed selective associations. Smoking and alcohol consumption were not independently associated with semen impairment.DiscussionPreventive andrological care remains markedly underutilized, with most men seeking evaluation only after fertility becomes a concern. The high prevalence of seminal abnormalities at first assessment highlights a missed opportunity for earlier diagnosis and intervention. These findings highlight the underutilization of preventive andrological care during adolescence and early adulthood, emphasizing the importance of awareness of male reproductive health and timely clinical evaluation.
Alterations in the female reproductive tract microbiota have been associated with unexplained recurrent spontaneous abortion (URSA), yet the microbial features characterizing non-pregnant women with URSA remain poorly defined. In this study, we employed 16S rRNA gene sequencing to systematically profile vaginal and cervical bacterial communities in non-pregnant women with URSA and controls. The URSA group exhibited reduced Shannon diversity, particularly in vaginal samples, reflecting diminished community evenness rather than a loss of richness, while beta diversity analyses identified disease status as the primary determinant of microbial composition. Taxonomic analysis revealed a lower relative abundance of Actinobacteriota and higher relative abundances of Proteobacteria and selected anaerobic taxa in URSA. LEfSe analysis further suggested differences in the species-level composition of Lactobacillus between the Control and URSA groups. Additional enrichment of Gram-negative bacteria such as Escherichia–Shigella and Comamonadaceae, and anaerobic Clostridia was observed in URSA. The URSA and Control networks differed in node and edge counts, connectivity patterns, and modular organization. Chronic endometritis (CE) and age as significant drivers of microbial community structure, with genera such as Kingella, Pelomonas, and Propionimicrobium showing strong associations with CE and SAB. Collectively, these findings suggest that URSA is associated with differences in reproductive tract bacterial composition and co-occurrence patterns in the non-pregnant state. These insights provide a preliminary foundation for developing microbiome-based preconception screening strategies and targeted therapeutic interventions to improve reproductive outcomes.
BackgroundTo develop a Japanese population-specific empirical conversion between follitropin alfa IU and follitropin delta µg based on comparable ovarian response and to evaluate its response and clinical consistency.MethodsThis retrospective single-center cohort included 231 first cycles with follitropin alfa and 154 with follitropin delta. Overlap weighting balanced age, body weight, antral follicle count, anti-Müllerian hormone, basal FSH, and basal LH. Inverse response calibration incorporated oocyte yield, follicle-to-oocyte index (FOI), and follicular output rate (FORT). Five-fold cross-fitting assessed coefficient stability and held-out response equivalence. Follicular, endocrine, embryological, and reproductive outcomes were additionally compared at cross-fitted response-equivalent doses.ResultsThe conversion was follitropin delta (µg/day) = 4.581 + 0.02244 ×follitropin alfa (IU/day) (R2 = 0.704), corresponding to 7.95, 9.63, and 11.31 µg for 150, 225, and 300 IU. Fold-specific slopes ranged from 0.02144 to 0.02327 µg/IU. In held-out observations, FOI (difference −0.033; 90% CI, −0.097 to 0.031) and FORT (0.001; −0.097 to 0.100) met ±0.10 equivalence margins, whereas oocyte yield (−1.40; −2.65 to −0.15) did not meet the ±2-oocyte margin. Follicular, embryological, and cumulative reproductive outcomes were broadly consistent between preparations across response-equivalent dose levels.ConclusionThis Japanese population-specific conversion was stable across cross-fitting and supported response equivalence for FOI and FORT. Clinical outcome analyses further supported the consistency of the proposed response-equivalent dose relationship.Clinical trial registrationhttps://jrct.mhlw.go.jp/en-latest-detail/jRCT1031260453, This observational study was registered in the Japan Registry of Clinical Trials jRCT1031260453.
