{"title":"Multinucleation in the Human Embryo's First Mitosis: Linking Spindle Geometry Defects, SAC Tolerance, Chromosome Segregation, and Nuclear Envelope Reassembly.","authors":"Yuki Ono, Yukihiro Terada","doi":"10.1002/rmb2.70045","DOIUrl":"https://doi.org/10.1002/rmb2.70045","url":null,"abstract":"<p><strong>Background: </strong>Multinucleation occurs at high frequency during the first mitosis of human embryos and is associated with impaired developmental potential. Our live-imaging analyses showed that collapse of spindle geometry-such as low-aspect ratio spindles and pole defocusing-correlates with multinucleation, yet molecular links from aberrant spindle shape to multinucleation remain poorly defined.</p><p><strong>Methods: </strong>We performed a narrative review of published studies on spindle geometry control, kinetochore-microtubule attachment and error correction, spindle assembly checkpoint (SAC) signaling in oocytes and cleavage-stage embryos, chromosome transport, and telophase nuclear assembly, and organized the evidence to outline plausible mechanistic routes to multinucleation.</p><p><strong>Results: </strong>We propose that spindle-geometry defects increase kinetochore-microtubule misattachments and promote spatial dispersion of chromosomes. In early embryos, SAC signaling may limit the time window for correcting these errors, permitting anaphase onset with residual misattachments. In large embryonic cells (cleavage-stage blastomeres far larger than somatic cells), dispersed chromatin may be inefficiently reintegrated during telophase and incompletely enclosed during nuclear assembly, increasing the likelihood of persistent multinucleation.</p><p><strong>Conclusion: </strong>This review provides an integrated perspective linking spindle-shape failure to multinucleation during the first mitosis in human embryos, thereby informing mechanistic studies and contributing to advances in reproductive medicine and infertility treatment outcomes.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70045"},"PeriodicalIF":3.3,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623511","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":"Feasibility and Safety of Intraoperative Oocyte Retrieval in Patients With Ovarian Tumor: Results From the Japan Oncofertility Registry.","authors":"Futa Ito, Satoshi Kubota, Taro Yagi, Mizuho Akedo, Yuta Tsuji, Masahiko Takemura, Ken-Ichirou Morishige","doi":"10.1002/rmb2.70043","DOIUrl":"https://doi.org/10.1002/rmb2.70043","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the clinical utility and safety of intraoperative oocyte retrieval (IOR) as a fertility preservation (FP) strategy for patients with ovarian tumors using data from the Japan Oncofertility Registry (JOFR).</p><p><strong>Methods: </strong>This retrospective study analyzed data from 226 patients with ovarian tumors registered in the JOFR between November 2018 and July 2024. Among them, 49 patients received FP and oncologic treatment at the same institution, and 10 underwent IOR. Tumor characteristics, stimulation methods, retrieval procedures, oocyte yield, complications, recurrence, and pregnancy outcomes were reviewed.</p><p><strong>Results: </strong>Patients were aged 21-35 years, and histological types varied. IOR was performed in vivo in four patients, ex vivo in two, and using both approaches in two, whereas two patients underwent transvaginal oocyte retrieval under general anesthesia. No intraoperative complications were observed. Tumor recurrence occurred in only one metastatic case. Oocyte yield was limited. One patient conceived through timed intercourse, whereas a pregnancy achieved using cryopreserved oocytes resulted in miscarriage.</p><p><strong>Conclusions: </strong>IOR was technically feasible and safely performed in patients with ovarian tumors, with no retrieval-related complications or tumor recurrence. Although reproductive efficacy remains unclear, IOR may be considered a feasible FP option when conventional approaches are difficult to apply.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70043"},"PeriodicalIF":3.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623445","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}
Hsiu-Hui Chen, Chien-Hong Chen, Chun-Chia Huang, Pin Yao Lin, Tsung-Hsien Lee, Ming-Jer Chen, Maw-Sheng Lee, Chun-I Lee
{"title":"Impact of Inner Cell Mass Hatching Levels Before Vitrification on Clinical Pregnancy in Preimplantation Genetic Testing for Euploidy Cycles.","authors":"Hsiu-Hui Chen, Chien-Hong Chen, Chun-Chia Huang, Pin Yao Lin, Tsung-Hsien Lee, Ming-Jer Chen, Maw-Sheng Lee, Chun-I Lee","doi":"10.1002/rmb2.70036","DOIUrl":"https://doi.org/10.1002/rmb2.70036","url":null,"abstract":"<p><strong>Purpose: </strong>Does an association exist between the ICM/TE hatching levels of biopsied blastocysts before vitrification and implantation?</p><p><strong>Methods: </strong>Total 541 single blastocyst transfers in PGT-A cycles were collected. The degree of TE/ICM extrusion from the zona pellucida before vitrification was categorized as (1) ICM hatching level ≤ 50% and > 50%, (2) TE hatching level ≤ 25% and > 25%.</p><p><strong>Results: </strong>TE hatching levels were not associated with clinical pregnancy probability (<i>p</i> = 0.804). Multivariate regression analysis revealed a positive association between ICM hatching level ≤ 50% with implantation probability. Especially in the ICM Grade B group, blastocysts with ICM hatching level > 50% had a significantly lower clinical pregnancy rate (47.4%, 36/76) and ongoing pregnancy rate (39.5%, 30/76) than did blastocysts with ICM hatching levels of ≤ 50% (66.4%, 219/330 and 60.6%, 200/330, respectively) (<i>p</i> < 0.01). Additionally, the proportion of apoptotic ICM cells was significantly higher in the ICM hatching level of > 50% group (90.0%, 9/10) than that in the ICM hatching level of ≤ 50% group (23.1%, 9/39) (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Blastocysts with an ICM hatching level of > 50% had the lower implantation potential, which may be related to the increased incidence of ICM cell apoptosis.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70036"},"PeriodicalIF":3.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623549","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":"Advancements in Spermatogenesis In Vitro: From Murine Success to Human Applications.","authors":"Maki Kamoshita","doi":"10.1002/rmb2.70044","DOIUrl":"https://doi.org/10.1002/rmb2.70044","url":null,"abstract":"<p><strong>Background: </strong>Male infertility due to spermatogenic failure remains a global challenge. While in vitro spermatogenesis (IVS) offers potential for fertility preservation, recapitulating the complex, species-specific testicular niche remains a formidable task. This review evaluates IVS progress and bottlenecks across rodents, primates, domestic animals, and humans.</p><p><strong>Methods: </strong>This review summarizes a comprehensive literature synthesis of IVS methodologies, including organ culture, microfluidics, 3D organoids, and induced pluripotent stem cell (iPSC)-derived systems. Particular focus was placed on the technical evolution from the foundational gas-liquid interface method to the development of bioengineering platforms.</p><p><strong>Main findings: </strong>Murine IVS systems have successfully and consistently produced fertile offspring. Conversely, human and non-human primate models show meiotic arrest, with differentiation typically stagnating at pre-meiotic stages. Although domestic animal models have occasionally yielded haploid cells, efficiency remains low. Recent single-cell analyses suggest that disrupted somatic-germ cell communication is a key driver of these failures.</p><p><strong>Conclusion: </strong>Bridging the gap between rodent success and human application requires integrating developmental biology with precision engineering. Future efforts must focus on establishing rigorous epigenetic and functional validation to ensure the safety and efficacy of IVS for clinical reproductive medicine.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70044"},"PeriodicalIF":3.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623902","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":"Are the Previously Reported Risk Factors for Endometriosis Actually Associated With Pain and Infertility Rather Than Endometriosis Itself?","authors":"Sachiko Matsuzaki","doi":"10.1002/rmb2.70041","DOIUrl":"https://doi.org/10.1002/rmb2.70041","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis is often diagnosed late due to a lack of noninvasive diagnostic tools and the varied presentation of its symptoms. Identifying risk factors for endometriosis is crucial for reducing diagnosis delays, mitigating the disease's impact, and enabling earlier treatment.</p><p><strong>Methods: </strong>Original and review articles published in English were selected from PubMed and Google Scholar searches up to January 2026. The following keywords were used: endometriosis, pain, infertility, and risk factors. The search was performed using these keywords individually, as well as in combination.</p><p><strong>Main findings results: </strong>Several previously reported risk factors associated with endometriosis have also been linked to dysmenorrhea, chronic pain, and infertility. These are all major clinical manifestations of the disease. Additionally, some endometriosis risk factors are associated with depression. Mendelian randomization studies have revealed that depression can cause endometriosis, dysmenorrhea, chronic pain, and infertility. However, few previous studies have conducted subgroup analyses based on clinical manifestations to identify endometriosis risk factors.</p><p><strong>Conclusion: </strong>It is unclear whether the previously reported risk factors are associated with endometriosis itself or with its specific clinical manifestations, such as pain and infertility. Future epidemiological research evaluating potential risk factors should consider heterogeneous endometriosis populations and include appropriate controls.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70041"},"PeriodicalIF":3.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623913","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":"Toward Implantation-Assisting Technologies: Lessons From In Vivo and Ex Vivo Models.","authors":"Takehiro Hiraoka, Yasushi Hirota, Masahito Ikawa","doi":"10.1002/rmb2.70042","DOIUrl":"https://doi.org/10.1002/rmb2.70042","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in assisted reproductive technology (ART), embryo implantation remains inefficient and represents a major barrier to successful pregnancy. Recurrent implantation failure persists even after transfer of high-quality embryos, reflecting an incomplete understanding of the molecular mechanisms governing implantation.</p><p><strong>Methods: </strong>This review synthesizes current knowledge from genetically modified mouse models and an ex vivo system using authentic uterine tissue. Implantation is organized as a hierarchical, multistep process comprising acquisition of uterine receptivity, embryo attachment, and trophoblast invasion.</p><p><strong>Main findings: </strong>Uterine receptivity is acquired through the action of progesterone signaling. Embryo attachment requires FOXA2-mediated uterine gland maturation and activation of the LIF-STAT3 signaling axis. Subsequent invasion is driven by coordinated epithelial clearance, stromal differentiation, and embryonic activation. Disruption of these stage-specific mechanisms leads to implantation failure. To overcome experimental limitations inherent to in vivo models, an ex vivo uterine system has been developed that preserves native tissue architecture and enables direct manipulation of embryo-uterine interactions.</p><p><strong>Conclusion: </strong>Conceptualizing implantation as a hierarchical process reveals discrete regulatory checkpoints and identifies implantation as a biologically tractable target. Integration of mechanistic insights with ex vivo platforms supports the development of implantation-assisting technologies based on transient, trophectoderm-targeted interventions in next-generation reproductive medicine.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70042"},"PeriodicalIF":3.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623486","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":"Long-Read Sequencing of CAH and ADPKD Provides Novel Insights Into the Genetic Diagnosis of Male Infertility.","authors":"Xiao Li, Chang Liu, Wen Liu, Xianlong Wang, Jiaolong Liu, Feifei Cai, Shaoming Lu","doi":"10.1002/rmb2.70038","DOIUrl":"https://doi.org/10.1002/rmb2.70038","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the utility of long-read sequencing (LRS) in identifying variants of congenital adrenal hyperplasia (CAH) and autosomal dominant polycystic kidney disease (ADPKD) in infertile men, which may help further clarify genetic diagnosis and support genetic counseling and reproductive management.</p><p><strong>Methods: </strong>A total of 722 infertile men underwent next-generation sequencing (NGS) panel testing. LRS was subsequently applied to characterize variants of CAH and ADPKD. Semen parameters, serum sex hormone levels, and assisted reproductive outcomes were further analyzed in males carrying the relevant variants.</p><p><strong>Results: </strong>Definitive genetic diagnoses were established in 3.3% (24/722) of men by NGS panel. LRS directly determined the trans configurations of two <i>CYP21A2</i> variants in a subject with azoospermia. Eighty-seven infertile men with ADPKD-related variants were identified, including 7 subjects carrying pathogenic variants. About 96.6% of subjects had no familial history of PKD, and 85.0% of subjects had abnormal results of semen analysis. Overall, LRS added 33.3% diagnostic yield above for infertile men.</p><p><strong>Conclusions: </strong>The application of CAH and ADPKD analysis based on LRS extends conventional genetic testing for male infertility by enabling accurate evaluation of complex genomic regions, thereby improving diagnostic clarity and informing reproductive decision-making and clinical management.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70038"},"PeriodicalIF":3.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623551","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":"Micronized Vaginal Progesterone Dose and Serum Progesterone Thresholds Determine Reproductive Outcomes in Frozen-Thawed Embryo Transfer With Hormone Replacement Therapy.","authors":"Mami Sekiguchi, Ayumu Ito, Yukiko Katagiri, Masato Yoneyama, Takahiro Tsuchiya, Mayuko Furui, Nahomi Umemura, Hideyuki Kobayashi, Masahiko Nakata","doi":"10.1002/rmb2.70039","DOIUrl":"https://doi.org/10.1002/rmb2.70039","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the combined effects of micronized vaginal progesterone (P4) dose and achieved serum P4 levels on reproductive outcomes in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles by classifying patients according to both parameters.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 1137 single good-quality blastocyst transfers performed between 2017 and 2022. Patients received OneCrinone 90 mg/day, Lutinus 300 mg/day, or Luteum 800 mg/day. Serum P4 levels on the day of embryo transfer (ET) and assisted reproductive technology (ART) outcomes were compared, including dose-serum P4-based subgroup analyses. Receiver operating characteristic analysis was used to explore a serum P4 cutoff for clinical pregnancy.</p><p><strong>Results: </strong>Higher daily doses were associated with increased serum P4 levels and higher implantation, clinical pregnancy, and live birth rates. An exploratory serum P4 cutoff of 13.1 ng/mL on the day of ET was associated with clinical pregnancy, with significantly better outcomes observed in patients with P4 ≥ 13.1 ng/mL. Dose-serum P4-based subgroup analyses showed that both parameters jointly influenced ART outcomes.</p><p><strong>Conclusion: </strong>In HRT-FET cycles, achieving adequate micronized vaginal P4 dosage together with sufficient serum P4 levels on the ET day is associated with improved ART outcomes. Monitoring serum P4 may help support individualized luteal phase management.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70039"},"PeriodicalIF":3.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623460","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":"Endometrial Microbiome and Implantation: From Basic Knowledge to Clinical Medicine.","authors":"Daiki Hiratsuka, Mitsunori Matsuo, Yasushi Hirota","doi":"10.1002/rmb2.70040","DOIUrl":"https://doi.org/10.1002/rmb2.70040","url":null,"abstract":"<p><strong>Background: </strong>Recurrent implantation failure (RIF) is an infertility condition in which uterine factors remain difficult to diagnose and treat. Recent studies implicate the endometrial microbiome in implantation.</p><p><strong>Methods: </strong>This clinically oriented narrative review summarizes female reproductive tract microbiota and evidence on endometrial microbiome testing and management in infertility.</p><p><strong>Main findings results: </strong>Vaginal dysbiosis is linked to adverse reproductive outcomes and provides a reference for interpreting upper-tract findings. Endometrial microbial signals are detectable by sequencing, but interpretation is challenged by the low-biomass environment and vulnerability to carry-over, kitome effects, and contamination. Across ART studies, a <i>Lactobacillus</i>-enriched endometrial profile is more often associated with favorable pregnancy-related outcomes, whereas non-<i>Lactobacillus</i>-dominant patterns are more frequently reported in implantation failure, although effect sizes and statistical significance vary across cohorts and depend on sampling validity and cutoff definitions. Limited nonrandomized intervention studies suggest that testing-guided targeted management (typically antibiotics with or without vaginal <i>Lactobacillus</i>-containing probiotics) may benefit selected patients, but protocols are heterogeneous and results remain inconsistent.</p><p><strong>Conclusion: </strong>Evidence is rapidly evolving, yet observational designs and methodological variability limit causal inference. Future progress will require standardized sampling and contamination controls, outcome-anchored threshold validation, and pragmatic real-world evaluations of protocolized test-and-treat pathways using clinically meaningful endpoints.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70040"},"PeriodicalIF":3.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623939","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":"Live Birth Following Dibutyryl-cAMP-Enhanced Biphasic in Vitro Maturation of Ovarian Tissue Oocytes From a Patient With Ovarian Fibromatosis: A First Report.","authors":"Shotaro Higuchi, Tsutomu Miyamoto, Miho Mochizuki, Tamae Fukushima, Koichi Ida, Hisanori Kobara, Ayumi Ohya, Yasunari Fujinaga, Tanri Shiozawa","doi":"10.1002/rmb2.70024","DOIUrl":"https://doi.org/10.1002/rmb2.70024","url":null,"abstract":"<p><strong>Case: </strong>A 23-year-old nulligravida with bilateral ovarian fibromatosis, amenorrhea, and severe ovulatory dysfunction was diagnosed via laparoscopic biopsy. As pregnancy was desired but transvaginal oocyte retrieval was not feasible due to dense fibrosis, partial ovarian resection was performed, and oocytes were obtained using ovarian tissue oocyte in vitro maturation (OTO-IVM).</p><p><strong>Outcome: </strong>In the first OTO-IVM cycle with human chorionic gonadotropin (hCG) priming, 11 mature and 63 immature oocytes were retrieved. Mature oocytes underwent intracytoplasmic sperm injection (ICSI), whereas immature oocytes were cultured in vitro for maturation before ICSI. A total of 13 oocytes were fertilized, five embryos were cryopreserved, and one embryo transfer resulted in a biochemical pregnancy. At age 28, a second OTO-IVM using dibutyryl-cyclic AMP (dbcAMP)-enhanced biphasic IVM produced seven germinal vesicle oocytes; three matured to metaphase II, two fertilized, and one cleavage-stage embryo led to a live birth at 39 weeks of gestation.</p><p><strong>Conclusion: </strong>This is the first documented live birth following dbcAMP-enhanced biphasic IVM of ovarian tissue-derived oocytes. These findings suggest that dbcAMP-enhanced biphasic IVM may be a feasible option when granulosa cell support is limited, offering a potential addition to fertility preservation strategies.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70024"},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444945","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}