Donya Pourbagher, Rastin Bakhtiari Lafmejani, Parham Namdar, Arya Akhavan, Alireza Nikfarjam, Ali Soleimanzadeh
{"title":"Inflammation and Oxidative Stress in Male Infertility: A Narrative Review.","authors":"Donya Pourbagher, Rastin Bakhtiari Lafmejani, Parham Namdar, Arya Akhavan, Alireza Nikfarjam, Ali Soleimanzadeh","doi":"10.1002/rmb2.70090","DOIUrl":"https://doi.org/10.1002/rmb2.70090","url":null,"abstract":"<p><strong>Background: </strong>Male infertility affects 8%-15% of couples, with male factors implicated in about half of cases; many remain idiopathic despite improved diagnostics. This narrative review addresses this gap by examining chronic inflammation as an underappreciated driver of sperm dysfunction that forms a bidirectional, self-reinforcing cycle with oxidative stress (OS).</p><p><strong>Methods: </strong>We synthesized studies from 2015 to 2025 identified via PubMed, Scopus, and Web of Science, examining links between inflammation and OS, key immune pathways, and related risk factors through qualitative narrative synthesis.</p><p><strong>Results: </strong>Inflammation drives leukocyte infiltration, blood-testis-barrier breakdown, antisperm-antibody production, and inflammasome activation, mechanisms that amplify OS and cause sperm DNA damage, impaired motility, apoptosis, and poor semen quality. Intrinsic factors (prostatitis, infection, varicocele) and extrinsic factors (obesity, aging, psychological stress) sustain this cycle through both ROS-dependent and ROS-independent, immune-mediated pathways. Paternal inflammation may also induce epigenetic changes in sperm with potential consequences for offspring health.</p><p><strong>Conclusion: </strong>Antioxidant monotherapy alone is often insufficient when an underlying immune driver persists. Immune-focused diagnostics combined with individualized, mechanism-based treatment strategies may improve personalized care and fertility outcomes.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70090"},"PeriodicalIF":4.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alteration in Lipid Metabolism Associated With Recurrent Pregnancy Loss: An Observational Case-Control Study.","authors":"Yuta Uchimura, Lianhua Shen, Shinobu Goto, Hiroyuki Yoshihara, Chihiro Banno, Tamao Kitaori, Chunyan Yu, Fangfang Wang, Eiji Matsuura, Mayumi Sugiura-Ogasawara","doi":"10.1002/rmb2.70087","DOIUrl":"10.1002/rmb2.70087","url":null,"abstract":"<p><strong>Purpose: </strong>No biomarkers specific to true unexplained recurrent pregnancy loss (RPL) have yet been identified. This study aimed to investigate the lipid profile of patients with unexplained RPL using metabolomic analyses.</p><p><strong>Methods: </strong>Comprehensive serum metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry. Lipid metabolites were analyzed using orthogonal partial least squares discriminant analysis.</p><p><strong>Results: </strong>The final analysis included serum samples from 31 healthy non-pregnant controls, 15 healthy pregnant controls, 32 non-pregnant patients with RPL, 19 pregnant patients with RPL and euploid miscarriage, and 30 pregnant patients with RPL and aneuploid miscarriage. Compared with controls, the non-pregnant RPL group exhibited higher levels of inflammation-related metabolites, including 11-dehydro-thromboxane B2 (11-dehydro-TXB2), 12-hydroxyeicosatetraenoic acid (HETE), and prostaglandin E2 (PGE2). Pregnant controls showed increased arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolites. Comparisons between pregnant controls and patients with euploid or aneuploid miscarriages showed no clear separation. Enzyme-linked immunosorbent assay confirmed elevated serum 11-dehydro-TXB2 in non-pregnant patients with RPL.</p><p><strong>Conclusion: </strong>Patients with RPL display a distinct serum lipid signature in the non-pregnant state, characterized by elevated levels of pro-thrombotic and pro-inflammatory eicosanoids, including 11-dehydro-TXB2, 12-HETE, and PGE2. Further studies are warranted to clarify the potential utility of 11-dehydro-TXB2 as biomarkers for RPL.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70087"},"PeriodicalIF":4.3,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Age-Specific Gonadotoxic Alkylating-Agent Exposure in Pediatric and Reproductive-Age Females: A Claims-Based Study Using Cyclophosphamide Equivalent Dose.","authors":"Kentaro Taniguchi, Mizuki Ohashi, Yuji Tanaka, Tetsuro Hanada, Akie Takebayashi, Akimasa Takahashi, Tsukuru Amano, Shunichiro Tsuji","doi":"10.1002/rmb2.70084","DOIUrl":"10.1002/rmb2.70084","url":null,"abstract":"<p><strong>Purpose: </strong>To describe age-specific patterns of gonadotoxic alkylating-agent exposure and evaluate how the cyclophosphamide equivalent dose (CED) framework captures real-world exposure relevant to fertility preservation in females aged 0-43 years.</p><p><strong>Methods: </strong>This descriptive study used a Japanese claims database. Patients were classified as pediatric (< 15 years) or reproductive-age (15-43 years). Twelve alkylating agents were evaluated, and six CED-calculable agents were converted to CED.</p><p><strong>Results: </strong>Among approximately 3.86 million females, 0.04% of the pediatric cohort and 0.16% of the reproductive-age cohort were exposed to at least one alkylating agent. Total CED identified at least intermediate-risk exposure in 33% of exposed pediatric and 14% of exposed reproductive-age patients. Compared with single-agent assessment, summed total CED identified additional patients mainly in the pediatric group, corresponding to relative increases of 20.2% and 0.3%, respectively. Agents not included in the current CED formula accounted for 8.7% of all alkylating-agent prescription records, approximately 90% of which were observed in reproductive-age patients.</p><p><strong>Conclusions: </strong>CED captured alkylating-agent exposure differently by age group: summed CED added exposure information mainly in pediatric patients, whereas agents lacking conversion coefficients limited exposure capture in reproductive-age females. These findings support refinement of CED-based assessment while emphasizing exposure capture, not outcome prediction.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70084"},"PeriodicalIF":4.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Library Concentration After Whole Genome Amplification Improves Interpretation of Spent Culture Medium-Based Noninvasive PGT-A in Vitrified-Warmed Human Blastocysts.","authors":"Shota Oikawa, Tatsuya Kobayashi, Takuma Kishida, Kyoko Higuchi, Eriko Sakakibara, Yuka Inui, Kyota Ashikawa, Goro Kuramoto, Teruyuki Yamasaki, Shin Tada, Hironori Miyamura, Eiji Nishio, Haruki Nishizawa, Toshio Hamatani","doi":"10.1002/rmb2.70085","DOIUrl":"10.1002/rmb2.70085","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the feasibility and performance of spent culture medium (SCM)-based non-invasive pre-implantation genetic testing for aneuploidy (niPGT-A) after 8 h of post-warming in vitrified-warmed human blastocysts, and to determine whether post-amplification library concentration improves SCM-based result interpretation.</p><p><strong>Methods: </strong>This study included 26 discarded vitrified-warmed blastocysts from 17 patients. After 8 h of post-warming culture, SCM was collected and analyzed by next-generation sequencing together with trophectoderm (TE) biopsy samples and whole blastocysts (WB). Concordance at the chromosome and category levels was evaluated between SCM and WB and between TE biopsy and WB, and the association of library concentration with performance and euploid probability was assessed.</p><p><strong>Results: </strong>SCM analysis was informative in 92.3% (24/26) of embryos. Chromosome-level concordance with WB was lower for SCM than for TE (30.8% vs. 57.7%), whereas category-level concordance was 69.2% for SCM and 76.9% for TE. Combining SCM category with library concentration improved prediction of euploid embryos (AUC 0.9527 vs. 0.8077, <i>p</i> = 0.0158). The leave-one-out cross-validated AUC of the combined model was 0.896.</p><p><strong>Conclusions: </strong>SCM-based niPGT-A after 8 h of post-warming culture is feasible in vitrified-warmed human blastocysts. Library concentration improves interpretation of SCM-based results and may help identify embryos likely to be euploid.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70085"},"PeriodicalIF":4.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tacrolimus Modulates Peripheral Blood NK Cell Subsets and IL-17/IL-10 Ratio in Women With Recurrent Implantation Failure.","authors":"Marzieh Zamaniyan, Sepideh Peivandi, Imaneh Ahmadi, Fatemeh Ghasemzadeh, Mohammad Malekan, Behshad Bahri, Maryam Lotfi, Hossein Asgarian-Omran, Saeid Taghiloo","doi":"10.1002/rmb2.70083","DOIUrl":"10.1002/rmb2.70083","url":null,"abstract":"<p><strong>Purpose: </strong>Recurrent implantation failure (RIF) is linked to immune dysregulation. Although tacrolimus has shown clinical benefits in RIF, its immunological mechanisms remain unclear. We assessed its effects on peripheral blood NK cell subsets and cytokine profiles.</p><p><strong>Methods: </strong>Thirty women with RIF and 30 fertile controls were enrolled. Patients received oral tacrolimus (3 mg/day) before embryo transfer until pregnancy testing. NK cell subsets and IL-17/IL-10 expression were assessed by flow cytometry and real-time PCR before and after treatment.</p><p><strong>Results: </strong>At baseline, RIF patients showed higher NK cell-associated subsets and increased IL-17/IL-10 ratio compared with controls (CD16<sup>+</sup>: <i>p</i> = 0.019; CD56<sup>+</sup>: <i>p</i> < 0.0001; CD16<sup>+</sup>CD56<sup>+</sup>: <i>p</i> < 0.0001; IL-17/IL-10 ratio: <i>p</i> < 0.0001). Following tacrolimus, CD16<sup>+</sup> (<i>p</i> = 0.011), CD56<sup>+</sup> (<i>p</i> = 0.001), and CD16<sup>+</sup>CD56<sup>+</sup> (<i>p</i> = 0.001) NK cells, as well as IL-17 levels (<i>p</i> < 0.0001) and the IL-17/IL-10 ratio (<i>p</i> = 0.0036), were significantly reduced, whereas IL-10 expression remained unchanged (<i>p</i> = 0.406). Greater reductions in the IL-17/IL-10 ratio were associated with clinical pregnancy (<i>p</i> = 0.048), suggesting predictive value for implantation success.</p><p><strong>Conclusions: </strong>Tacrolimus modulated immune pathways by reducing pro-inflammatory NK subsets and shifting the IL-17/IL-10 balance toward tolerance, supporting its potential as targeted immunotherapy in selected patients.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70083"},"PeriodicalIF":4.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Outcomes of Postponing Oocyte Retrieval Beyond 40 h After Trigger With Diclofenac Pretreatment Compared With the Routine Paradigm: A Retrospective Propensity Score-Matched Study.","authors":"Rang Liu, Xinyi Pan, Rui Xiang, Yutong Wang, Shaohong Zhuang, Jiana Huang, Cong Fang, Xiaoyan Liang, Haitao Zeng","doi":"10.1002/rmb2.70079","DOIUrl":"10.1002/rmb2.70079","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare outcomes of delaying oocyte retrieval beyond 40 h post-trigger with diclofenac versus the conventional workflow.</p><p><strong>Methods: </strong>A total of 4912 cycles were retrospectively screened. Eighty-four delayed cycles and 168 routine cycles from patients who received a single trigger in their first cycle were matched at a 1:2 ratio for age, AMH, COS protocol, and ICSI use and compared.</p><p><strong>Results: </strong>The ratio of the number of oocytes retrieved to the number of follicles ≥ 14 mm on trigger day was significantly higher in the delayed group (1.27 ± 0.42 vs. 1.14 ± 0.47, <i>p</i> = 0.031). The rates of maturation (78.9% vs. 78.8%), fertilization (64.0% vs. 64.6%), and blastulation (63.8% vs. 68.5%) were comparable (all <i>p</i> > 0.05). Biochemical pregnancy rates in fresh cycles were numerically lower in the delayed group (38.4% vs. 47.0%), while clinical pregnancy rates were similar between groups in both fresh (38.4% vs. 41.1%) and frozen-thawed cycles (51.2% vs. 52.8%) (all <i>p</i> > 0.05).</p><p><strong>Conclusions: </strong>Delaying oocyte retrieval beyond 40 h post-trigger with diclofenac could be feasible to enhance clinical operational flexibility. Further research is warranted to identify subgroups that may benefit most and to optimize strategies adapted to this extension.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70079"},"PeriodicalIF":4.3,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Time-Lapse Culture Improves Development and Pregnancy Outcomes of Sibling Normally Fertilized Oocytes: A Prospective Multicenter Study.","authors":"Yasuyuki Mio, Takeshi Kuramoto, Takafumi Utsunomiya, Seung Chik Jwa, Keitaro Yumoto, Panagiota Tsounapi","doi":"10.1002/rmb2.70077","DOIUrl":"10.1002/rmb2.70077","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether time-lapse monitoring improves embryological outcomes and clinical pregnancy rates compared to conventional culture in a sibling-oocyte study.</p><p><strong>Methods: </strong>This multicenter-study involved 205 first-time retrieval cycles (<i>n</i> = 3244 mature oocytes). Sibling-oocytes from patients with ≥ 4 oocytes were randomized into conventional and time-lapse groups. The primary outcome was the good-quality blastocyst rate. Key secondary outcomes included Day-2 Good Quality Embryo (GQE) rates and clinical pregnancy rates for both fresh and frozen-thawed embryo transfers (FET).</p><p><strong>Results: </strong>The time-lapse group exhibited a significantly higher GQE rate on Day 2 (42.1% vs. 35.3%, <i>p</i> < 0.01) and a higher good-quality blastocyst rate (44.1% vs. 38.1%, <i>p</i> < 0.01) compared to the conventional group. While clinical pregnancy rates showed a higher trend in the time-lapse group for both fresh ET (44.4% vs. 15.8%) and FET (45.3% vs. 36.7%), these differences did not reach statistical significance. Time-lapse monitoring successfully identified embryos with early pronuclear disappearance as early as 14 h post-insemination. Morphokinetic analysis revealed that abnormal cleavage patterns were associated with significantly lower blastocyst development potential compared to normal cleavage (<i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>Time-lapse culture provides a stable environment that enhances embryo quality. While clinical pregnancy rates showed a positive trend, further large-scale studies are needed to confirm the impact on live birth rates.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70077"},"PeriodicalIF":4.3,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Personalized Embryo Transfer Improves Live Birth Rates in Recurrent Implantation Failure: A Propensity Score-Matched Prospective Cohort Study With Window of Implantation Stability Analysis.","authors":"Yasuhiro Ohara, Kurumi Abe, Saki Saito, Aya Karino, Masakazu Doshida, Takumi Takeuchi, Hidehiko Matsubayashi, Tomomoto Ishikawa, Mika Handa, Tsuyoshi Takiuchi, Michiko Kodama","doi":"10.1002/rmb2.70081","DOIUrl":"10.1002/rmb2.70081","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the clinical efficacy of ERPeak<sup>SM</sup>-guided personalized embryo transfer (pET) in recurrent implantation failure (RIF) and non-RIF patients, and assess the temporal stability of the window of implantation (WOI).</p><p><strong>Methods: </strong>This prospective cohort study included patients undergoing frozen embryo transfer (FET) with good-quality embryos. In hormone replacement therapy (HRT) cycles, RIF patients received pET (<i>n</i> = 199) or non-personalized ET (npET, <i>n</i> = 272); non-RIF patients received pET (<i>n</i> = 74) or npET (<i>n</i> = 351). Propensity score matching (PSM) adjusted for confounders. modified Natural cycle (mNC) FET was analyzed using inverse probability of treatment weighting (IPTW). WOI stability was evaluated via Kaplan-Meier analysis.</p><p><strong>Results: </strong>Following PSM in RIF patients, pET significantly improved live birth rates (LBR) compared to npET (41.0% vs. 23.6%, <i>p</i> < 0.001) and reduced miscarriage rates (17.4% vs. 36.2%, <i>p</i> = 0.014). In non-RIF patients, pET did not improve LBR (35.8% vs. 25.4%, <i>p</i> = 0.26). IPTW-adjusted mNC-FET analysis showed significantly higher LBR in the pET group (46.3% vs. 19.2%, <i>p</i> = 0.026). Kaplan-Meier analysis revealed WOI stability declines significantly faster in patients ≥ 38 years (median 30.0 months, <i>p</i> = 0.0059).</p><p><strong>Conclusions: </strong>ERPeak<sup>SM</sup>-guided pET significantly improves LBR in RIF patients undergoing HRT and mNC-FET, but lacks benefit in non-RIF patients. WOI is dynamic; reevaluation is recommended for older patients.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70081"},"PeriodicalIF":4.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hormonal Therapy Before Sperm Retrieval in Men With Non-Obstructive Azoospermia: From Controversy to Precision Using the APHRODITE Criteria.","authors":"Sandro C Esteves","doi":"10.1002/rmb2.70080","DOIUrl":"10.1002/rmb2.70080","url":null,"abstract":"<p><strong>Purpose: </strong>To review the biological rationale, clinical evidence, limitations, and future directions for hormonal therapy before sperm retrieval in men with non-obstructive azoospermia (NOA), with emphasis on phenotype-based selection using the APHRODITE criteria.</p><p><strong>Methods: </strong>A narrative review was conducted, integrating evidence on hypothalamic-pituitary-gonadal axis regulation, Leydig- and Sertoli-cell function, intratesticular testosterone, gonadotropin-based stimulation, sperm retrieval outcomes, and endocrine phenotyping in NOA. Particular attention was given to mechanistic studies and controlled cohorts evaluating hCG, FSH, or combined gonadotropin therapy before microdissection testicular sperm extraction.</p><p><strong>Results: </strong>Hormonal therapy in NOA remains controversial because available studies are heterogeneous and largely observational. However, mechanistic data show that hormonal therapy using hCG can increase intratesticular testosterone and stimulate spermatogonial activity, while exogenous FSH may support Sertoli-cell function. Clinical evidence suggests that benefit is most likely in selected men with biochemical hypogonadism, especially those with normal or moderately elevated FSH, whereas men with advanced hypergonadotropic testicular failure appear less likely to respond.</p><p><strong>Conclusions: </strong>Hormonal therapy before sperm retrieval in testicular NOA should be considered a selective, off-label strategy rather than a universal intervention. APHRODITE-based stratification may help identify candidates for endocrine optimization and guide future randomized trials.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70080"},"PeriodicalIF":4.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Positive and Negative Aspects of Public Insurance Coverage on ART With Respect to Multiple Gestation in Japan.","authors":"Aisaku Fukuda, Hiroshi Matsumoto, Isao Tsuji, Satoko Fujioka, Yoshiharu Morimoto","doi":"10.1002/rmb2.70078","DOIUrl":"10.1002/rmb2.70078","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined whether the application of public insurance on assisted reproductive technology in Japan was associated with changes in the incidence of multiple blastocyst transfer (MBT) and subsequent multiple pregnancies (MP).</p><p><strong>Methods: </strong>A total of 2764 blastocyst transfer cycles performed at IVF Osaka Clinic from the pre-insurance period (January 2020-March 2022) were retrospectively compared with 4,326 cycles from the insurance period (April 2022-February 2025). MP was defined as two or more gestational sacs.</p><p><strong>Results: </strong>Baseline analysis showed that patients' age after insurance coverage was significantly younger with fewer previous ET attempts than pre-insurance. MBT rose from 5.8% pre-insurance to 20.1% under insurance, and MP increased from 0.7% to 2.6%, simultaneously. Insurance coverage was independently associated with a higher likelihood of MBT, an association most pronounced in the older age cohort. MBT exhibited the highest risk profile for MP. Significant upward trends in MBT and MP were observed as patients approached their final insured cycles.</p><p><strong>Conclusions: </strong>Findings suggest a correlation between insured cycle limits and clinical practice toward prioritizing per-cycle success. Although alleviating financial burden, the policy appears to be associated with increased MBT and MP, making it necessary to deliberate its impact on maternal and neonatal safety.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70078"},"PeriodicalIF":4.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}