Aris Kaltsas, Nikolaos Sofikitis, Michael Chrisofos
{"title":"Male Reproductive Phenotype Heterogeneity in Varicocele: A Hypothesis-Generating Threshold-Resilience Framework and Research Agenda.","authors":"Aris Kaltsas, Nikolaos Sofikitis, Michael Chrisofos","doi":"10.1002/rmb2.70102","DOIUrl":"10.1002/rmb2.70102","url":null,"abstract":"<p><strong>Background: </strong>Varicocele is common in male infertility, yet many affected men retain conventional reproductive measures, and the anatomical grade is an imperfect proxy for phenotype. Established pathways explain injury more clearly than between-person heterogeneity.</p><p><strong>Methods: </strong>This structured, critical narrative review searched PubMed from 1 January 2015 to 26 August 2026, with targeted hand-searching. There was no preregistered protocol, dual screening, or risk-of-bias assessment, and coverage is not exhaustive.</p><p><strong>Main findings: </strong>The threshold-resilience framework is a hypothesis-generating model separating lesion-related exposure, candidate host response measures, and couple-level variables. Human varicocele-specific evidence supports hemodynamic, thermal, redox, and sperm DNA damage associations. No prospective human varicocele study was identified in which an independently measured antioxidant, DNA processing, heat response, or endocrine measure preserved fertility at a given exposure. Female age and ovarian reserve are couple-level variables, and all candidate host response measures remain research-only.</p><p><strong>Conclusion: </strong>Intended for investigators in andrology and reproductive medicine, the framework is a research agenda rather than an explanatory mechanism or clinical algorithm. It maps evidence provenance, identifies measurement gaps, and specifies prospective tests of whether prespecified, outcome-independent host response measures add prediction beyond anatomy, semen analysis, damage measures, and couple-level factors.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70102"},"PeriodicalIF":4.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216775","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":"Assisted Sperm Fusion Insemination: A Fusion-Based Approach to Fertilization Without Mechanical Oolemma Penetration.","authors":"Shota Hatakeyama","doi":"10.1002/rmb2.70106","DOIUrl":"https://doi.org/10.1002/rmb2.70106","url":null,"abstract":"<p><strong>Background: </strong>Intracytoplasmic sperm injection (ICSI) is widely used in assisted reproductive technology and achieves fertilization by directly injecting a spermatozoon into the oocyte cytoplasm. However, it requires deliberate disruption of the oolemma and bypasses physiological sperm-oocyte membrane fusion. Assisted sperm fusion insemination (ASFI) was developed to achieve fertilization through gamete membrane fusion without penetrating the oolemma.</p><p><strong>Methods: </strong>This review summarizes the biological basis of sperm fusion competence, including acrosomal exocytosis, zona pellucida interaction, and molecular mechanisms of gamete membrane fusion, and reviews the development, technical procedure, clinical evidence, and current limitations of ASFI.</p><p><strong>Results: </strong>ASFI uses motile zona pellucida-bound spermatozoa that are recovered and pressed against the oolemma to facilitate membrane adhesion and fusion. Clinical studies have demonstrated fertilization, blastocyst development, and live birth after ASFI. In a prospective sibling-oocyte study, ASFI achieved a higher normal fertilization rate than conventional ICSI (88.0% vs. 70.2%), with no oocyte degeneration (0% vs. 8.8%) and a higher usable embryo rate per MII oocyte (45.8% vs. 28.1%).</p><p><strong>Conclusion: </strong>ASFI provides a fusion-based alternative to direct sperm injection and may reduce procedure-related oocyte degeneration. Further studies are required to establish zona-independent sperm selection, technical standardization, and reproducibility across centers.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70106"},"PeriodicalIF":4.3,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169697","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}
Yusuke Mori, Hiroshi Kishi, Ayako Hasunuma, Yuta Kasahara, Aikou Okamoto
{"title":"Cabergoline Suppresses FSH-Induced Differentiation and Steroidogenesis in Primary Cultured Rat Granulosa Cells.","authors":"Yusuke Mori, Hiroshi Kishi, Ayako Hasunuma, Yuta Kasahara, Aikou Okamoto","doi":"10.1002/rmb2.70104","DOIUrl":"10.1002/rmb2.70104","url":null,"abstract":"<p><strong>Purpose: </strong>Cabergoline, a dopamine D<sub>2</sub> receptor agonist widely used to prevent ovarian hyperstimulation syndrome (OHSS), has unclear effects on granulosa cells during the follicular phase. This study aimed to investigate how cabergoline affects follicle-stimulating hormone (FSH)-induced cell differentiation and steroidogenesis.</p><p><strong>Methods: </strong>Primary granulosa cells were isolated from immature female rats pretreated with diethylstilbestrol (DES) and cultured under four conditions: control, cabergoline alone, FSH alone, and FSH combined with cabergoline. mRNA expression of <i>Lhcgr</i>, <i>Cyp19a1</i>, and related genes was quantified by real-time PCR, and luteinizing hormone (LH) receptor binding, estradiol (E<sub>2</sub>) and progesterone (P<sub>4</sub>) secretion, and cyclic adenosine monophosphate (cAMP) production were evaluated. Dopamine D<sub>2</sub> receptor expression was analyzed by Western blotting.</p><p><strong>Results: </strong>Cabergoline significantly suppressed FSH-induced mRNA expression of <i>Lhcgr</i>, <i>Cyp19a1</i>, <i>Cyp11a1</i>, and <i>Hsd3b1</i>; hCG binding; E<sub>2</sub> and P<sub>4</sub> secretion; and cAMP accumulation. Most inhibitory effects were dose dependent, although cAMP suppression did not exhibit clear concentration dependency. Dopamine D<sub>2</sub> receptor expression was detectable, although at low levels.</p><p><strong>Conclusions: </strong>Cabergoline suppresses FSH-induced granulosa cell differentiation and steroidogenesis, at least partly through attenuation of FSH-induced cAMP signaling. Although dopamine D<sub>2</sub> receptor signaling may contribute to the inhibitory effects of cabergoline, the downstream molecular mechanisms remain unclear, warranting further investigation.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70104"},"PeriodicalIF":4.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138098","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":"A Prospective Study on Clinical Utility of Preimplantation Genetic Testing for Aneuploidy and Structural Rearrangement Under Advanced Medical Care B in Japan.","authors":"Tsuyoshi Takiuchi, Fumie Saji, Mika Handa, Nao Wakui, Tatsuya Nakano, Ryota Kobayashi, Yoshie Nagatakidani, Tatsuya Miyake, Takeshi Iwasa, Akira Kuwahara, Minoru Irahara, Yoshiharu Nakaoka, Aisaku Fukuda, Yoshiharu Morimoto, Tomomi Yamada, Michiko Kodama, Tadashi Kimura","doi":"10.1002/rmb2.70101","DOIUrl":"10.1002/rmb2.70101","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the clinical utility of preimplantation genetic testing for aneuploidy and structural rearrangements (PGT-A/SR) under Advanced Medical Care B in Japan.</p><p><strong>Methods: </strong>This prospective, single-arm, multicenter benchmarking study included couples with recurrent implantation failure, recurrent pregnancy loss, or structural chromosomal rearrangements who underwent PGT-A/SR and first transfer of a category A/B embryo. The primary endpoint was ongoing pregnancy rate per transfer (oPR) at 12-13 weeks; clinical pregnancy rate (cPR) was prespecified as supportive because the registry benchmark used cPR. Outcomes were compared with age-adjusted national registry thresholds using a one-sample proportion test with a normal approximation.</p><p><strong>Results: </strong>Of 375 couples, 344 underwent PGT-A/SR and 218 reached first transfer. oPR was 48.6% versus 42.4% (<i>p</i> = 0.064) and did not reach statistical significance; cPR was 57.8% versus 42.4% (<i>p</i> < 0.001). Miscarriage rate was 15.9% versus 23.4% (<i>p</i> = 0.045). In women aged 35-39 and 40-42 years, oPR and cPR exceeded age-adjusted thresholds, whereas no benefit was demonstrated in women aged < 35 years.</p><p><strong>Conclusions: </strong>On a per-transfer basis, PGT-A/SR was associated with higher cPR and lower miscarriage rate, particularly in women aged ≥ 35 years. Interpretation is limited by the single-arm design and the mismatch between the study endpoint and the registry comparator.</p><p><strong>Trial registration: </strong>This study was registered in the Japan Registry of Clinical Trials (jRCT) (jRCT1052220197).</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70101"},"PeriodicalIF":4.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138068","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":"Correction to \"Expression and Function of Meflin in Human Endometrial Decidualization\".","authors":"","doi":"10.1002/rmb2.70103","DOIUrl":"10.1002/rmb2.70103","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1002/rmb2.70048.].</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70103"},"PeriodicalIF":4.3,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063484","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":"Mitochondrial-Targeted Phytochemicals in Reproductive Aging: Mechanisms and Translational Potential.","authors":"Binarwan Halim, Hilma Putri Lubis, Rony Abdi Syahputra","doi":"10.1002/rmb2.70086","DOIUrl":"10.1002/rmb2.70086","url":null,"abstract":"<p><strong>Purpose: </strong>Reproductive aging is increasingly recognized as a major contributor to infertility in both women and men. Although traditionally linked to endocrine decline, emerging evidence suggests that mitochondrial dysfunction is a central mechanism underlying impaired gamete quality and reduced reproductive capacity. This review aimed to evaluate the role of mitochondrial deterioration in reproductive aging and to examine the therapeutic potential of mitochondrial-targeted phytochemicals.</p><p><strong>Methods: </strong>A narrative review of experimental, translational, and clinical studies was conducted focusing on mitochondrial dynamics, oxidative stress, bioenergetic impairment, and phytochemical-based interventions in reproductive aging. Relevant evidence involving oocytes, spermatozoa, and the reproductive microenvironment was critically synthesized.</p><p><strong>Results: </strong>Aging-associated mitochondrial dysfunction was consistently associated with impaired ATP production, excessive reactive oxygen species generation, mitochondrial DNA damage, and disrupted cellular homeostasis, leading to reduced oocyte competence, sperm motility, and embryonic development. Several phytochemicals, including resveratrol, quercetin, epigallocatechin gallate, astaxanthin, lycopene, berberine, and coenzyme Q10, demonstrated protective effects through modulation of SIRT1-PGC-1α, AMPK, Nrf2, and PINK1-Parkin signaling pathways.</p><p><strong>Conclusions: </strong>Targeting mitochondrial bioenergetics with phytochemicals may provide a promising strategy for preserving fertility and extending reproductive lifespan, although further large-scale clinical validation is required.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70086"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063681","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":"The Possibility and Characteristics of Senescence-Related Changes in Reproductive Tissues Such as the Ovary, Oviduct, and Uterus.","authors":"Koumei Shirasuna, Ayaka Shirota, Hisataka Iwata","doi":"10.1002/rmb2.70100","DOIUrl":"10.1002/rmb2.70100","url":null,"abstract":"<p><strong>Background: </strong>Senescence is characterized by a functional decline of cells or tissues, whereas aging refers to the passage of time. Aging and senescence have been viewed as potentially controllable processes, and research on their underlying mechanisms and countermeasures has progressed. With the increasing number of women of advanced maternal age, the decline in fertility is thought to be associated not only with reduced oocyte quality but also with aging and senescence of the reproductive organs-that is, age-related changes in the ovarian, oviduct (fallopian tube), and uterine environments.</p><p><strong>Methods and main findings: </strong>Findings from animal experiments and clinical studies have shown that age-related changes in the ovaries, oviducts (fallopian tubes), and uterus contribute to a decline in reproductive performance. This effect may be explained by the progression of cellular senescence, chronic inflammation, DNA damage, and mitochondrial dysfunction in these organs, leading to fibrosis and abnormal cellular differentiation. These hallmarks of aging are thought to contribute to reduced oocyte quality, diminished ovarian reserve, and ovulatory disorders. Furthermore, even when fertilization occurs, impaired embryo development may result, ultimately reducing endometrial receptivity and leading to decreased fertility.</p><p><strong>Conclusion: </strong>This review discusses the potential roles and significance of aging and senescence in reproductive tissues.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70100"},"PeriodicalIF":4.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040519","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":"A Pilot Study Beyond Ovarian Reserve: How AMH Levels Shape the Proteomic and Metabolic Landscape of the Follicle.","authors":"Rosamaria Militello, Bianca Bartoloni, Gabriella Pinto, Serena Camerini, Angela Amoresano, Francesca Paola Luongo, Paola Piomboni, Alice Luddi, Sara Marchiani, Tania Fiaschi, Tania Gamberi","doi":"10.1002/rmb2.70099","DOIUrl":"10.1002/rmb2.70099","url":null,"abstract":"<p><strong>Purpose: </strong>The follicular fluid (FF) microenvironment critically influences oocyte development, with Anti-Müllerian Hormone (AMH) serving as a primary marker of ovarian reserve. This exploratory pilot study investigates the biochemical and proteomic shifts across the AMH spectrum to provide initial insights into potential targeted intrafollicular strategies.</p><p><strong>Methods: </strong>FF samples from 49 patients undergoing assisted reproduction were grouped into Low-, Normal-, and High-AMH groups. Oxidative stress, antioxidant capacity, and metabolic indicators (lactate, adiponectin) were analyzed. Proteomic profiling was performed via LC-ESI-MS/MS, followed by STRING network and Spearman correlation analyses.</p><p><strong>Results: </strong>Distinct molecular shifts occurred across groups. The High-AMH group showed a marked oxidative imbalance. Conversely, the Low-AMH group exhibited a distinct signature with higher lactate, lower adiponectin, and downregulated immunoglobulins, alongside upregulated HRG, ITIH3, and GPLD1. Positive correlations between adiponectin and immunoglobulins in Low-AMH subjects suggest that metabolic and immune-related factors may be coordinately regulated.</p><p><strong>Conclusions: </strong>This study suggests that AMH levels are associated with specific follicular microenvironment shifts. Low AMH levels appear linked to a distinct profile characterized by immune and metabolic alterations. These findings provide an exploratory foundation for future larger-cohort investigations into follicular homeostasis.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70099"},"PeriodicalIF":4.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040482","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}
Jan Gruszczyński, Kacper Trębacz, Beata Kubiaczyk-Paluch, Grzegorz Dworacki, Michał J Dopierała, Agata Kolecka-Bednarczyk, Andrzej Frankowski, Miłosz Kadziński, Tomasz Żak
{"title":"Plasma Cell Counting Methodology Determines Chronic Endometritis Prevalence.","authors":"Jan Gruszczyński, Kacper Trębacz, Beata Kubiaczyk-Paluch, Grzegorz Dworacki, Michał J Dopierała, Agata Kolecka-Bednarczyk, Andrzej Frankowski, Miłosz Kadziński, Tomasz Żak","doi":"10.1002/rmb2.70094","DOIUrl":"10.1002/rmb2.70094","url":null,"abstract":"<p><strong>Purpose: </strong>Histopathological assessment of plasma cells (PCs) via CD138 immunohistochemistry, the diagnostic gold standard for chronic endometritis (CE), is methodologically heterogeneous. Does reported variation in CE prevalence reflect underlying pathobiology, or is it primarily an artifact of counting methodology? We quantified how HPF selection strategy, field count, and magnification influence observed prevalence.</p><p><strong>Methods: </strong>We retrospectively studied 886 treatment-naïve patients suspected of CE. CD138-stained biopsies were digitized; a three-pathologist consensus reference validated an AI pipeline for PC detection. Four counting methods were applied across two magnifications (200× vs. 400×) and multiple thresholds.</p><p><strong>Results: </strong>Inter-observer reliability was higher for digital (ICC = 0.99) than microscopy-based assessment (ICC = 0.73). The AI pipeline (F1: 0.89-0.97) outperformed manual microscopy (F1: 0.67-0.89) and matched digital assessment (F1: 0.81-1.00). At a fixed threshold and field count (≥ 5 PCs, ×400, 10 HPFs), field-selection strategy alone shifted prevalence from 3.1% (Random Sampling) to 69.5% (Independent Hotspot), <i>p</i> < 0.001. Magnification also significantly altered CE classification (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>Diagnostic threshold alone does not fully specify a CE criterion; field-selection strategy, field count, and magnification must also be reported for prevalence estimates to be comparable. Hotspot-based and AI-assisted counting are recommended over random field selection for reproducibility and sensitivity.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70094"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991350","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":"Influences of 5-Hydroxytryptamine Receptor Agonists on Spermatozoal Hyperactivation and In Vitro Fertilization Success in Mice.","authors":"Gaku Nakamura, Masakatsu Fujinoki, Takao Kamai","doi":"10.1002/rmb2.70092","DOIUrl":"10.1002/rmb2.70092","url":null,"abstract":"<p><strong>Purpose: </strong>In mice, 5-hydroxytryptamine (5-HT) enhances hyperactivation through 5-HT<sub>2</sub>, 5-HT<sub>3</sub>, 5-HT<sub>4</sub>, and 5-HT<sub>7</sub> receptors and increases in vitro fertilization (IVF) success through the 5-HT<sub>4</sub> receptor. In the present study, we examined the effects of 5-HT receptor agonists on motility, hyperactivation, motility kinematics, and IVF success in mice.</p><p><strong>Methods: </strong>Spermatozoa were incubated for 4 h at 37°C under 5% CO<sub>2</sub> in modified Tyrode's albumin lactate pyruvate medium to induce hyperactivation. Motility and hyperactivation were analyzed using a video microscope. Motility kinematics were evaluated using the Sperm Motility Analysis System. IVF was performed by co-incubation of spermatozoa and oocytes for 0.5 and 5 h.</p><p><strong>Results: </strong>5-HT receptors were detected. 5-HT<sub>2</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and 5-HT<sub>4</sub> receptor agonists significantly enhanced hyperactivation and increased IVF success. 5-HT<sub>3</sub> and 5-HT<sub>7</sub> receptor agonists slightly enhanced hyperactivation but did not affect IVF success. These agonists did not affect motility. During hyperactivation, the velocities of motility kinematics decreased. 5-HT<sub>2</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and 5-HT<sub>4</sub> receptor agonists accelerated the decrease in velocities.</p><p><strong>Conclusion: </strong>These results suggest that 5-HT<sub>2</sub> and 5-HT<sub>4</sub> receptors participate in the enhancement of hyperactivation and the increase in IVF success in mice. The influence of the 5-HT<sub>4</sub> receptor agonist is stronger than that of the 5-HT<sub>2</sub> receptor agonists.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"25 1","pages":"e70092"},"PeriodicalIF":4.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991255","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}