Reproductive biomedicine online最新文献

{"title":"Fully Hatched Blastocysts: A Predictor of Success or a Potential Risk in Embryo Transfer?","authors":"Feyyaz Ozel ,&nbsp;Fazilet Kubra Boynukalin ,&nbsp;Bilgen Teke ,&nbsp;Meral Gultomruk ,&nbsp;Neslihan Sonmez ,&nbsp;Sinan Ozkavukcu ,&nbsp;Mustafa Bahceci ,&nbsp;Gurkan Bozdag","doi":"10.1016/j.rbmo.2025.105321","DOIUrl":"10.1016/j.rbmo.2025.105321","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To evaluate whether fully hatched blastocysts result in comparable clinical pregnancy and live birth rates, and to assess miscarriage risk in comparison with expanded/hatching blastocysts following frozen-thawed single embryo transfer.</div></div><div><h3>MATERIALS AND METHODS</h3><div>A retrospective cohort study was conducted at Bahceci IVF Center between November 2018 and January 2024. A total of 286 single fully hatched frozen-thawed blastocyst transfers (FBTs) were compared with 574 age- and PGT-A-matched expanded/hatching blastocyst FBTs (controls). Primary outcome: Live birth rate (LBR). Secondary outcomes: Clinical pregnancy rate (CPR) and miscarriage rate (MR). Subgroup analysis was performed for euploid-only transfers.</div></div><div><h3>RESULTS</h3><div>Demographic and embryological parameters were similar across groups. In the total cohort:</div><div>CPR: 48.3% (hatched) vs 46.7% (control), p = 0.71</div><div>LBR: 35.0% vs 38.3%, p = 0.37</div><div>MR: 26.8% vs 17.9%, p = 0.037</div><div>In the euploid-only subset:</div><div>CPR: 52.3% vs 49.3%, p = 0.59</div><div>LBR: 37.9% vs 42.6%, p = 0.39</div><div>MR: 27.5% vs 13.4%, p = 0.014</div><div>Logistic regression identified Day 5 freezing, embryo quality, and PGT-A use as independent predictors of live birth.</div></div><div><h3>CONCLUSIONS</h3><div>Fully hatched blastocyst transfer does not adversely impact live birth rates, but is associated with a significantly higher miscarriage rate, particularly in euploid transfers. These findings highlight a potential influence on early pregnancy outcomes and suggest the need for cautious consideration when selecting fully hatched embryos for transfer.</div></div><div><h3>IMPACT STATEMENT</h3><div>Fully hatched blastocysts may not reduce live birth rates but are linked to higher miscarriage risk, especially in euploid transfers. These findings suggest a need to reconsider transfer timing and embryo selection strategies.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105321"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixed vs Flexible Progestin-Primed Ovarian Stimulation in Social Fertility Preservation: Outcomes and Clinical Practicality","authors":"Sinem Ertas ,&nbsp;Irem Usta Korkut ,&nbsp;Cengiz Alatas ,&nbsp;Ayse Seyhan Ata ,&nbsp;Kayhan Yakin ,&nbsp;Oguzhan Bulduk ,&nbsp;Basak Balaban ,&nbsp;Cumhur Bulent Urman","doi":"10.1016/j.rbmo.2025.105325","DOIUrl":"10.1016/j.rbmo.2025.105325","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To compare the clinical outcomes and practical implications of fixed versus flexible PPOS (Progestin-Primed Ovarian Stimulation) protocols for pituitary suppression in women undergoing social fertility preservation.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective cohort study included women aged 18–45 undergoing elective oocyte cryopreservation with PPOS (n:381) between June 2022 and January 2025 at a single tertiary fertility center. Patients received either a fixed PPOS protocol (n:246), with progestin (10 mg medroxyprogesterone acetate -MPA-) initiated on the first day of ovarian stimulation, or a flexible PPOS protocol (n:135), where progestin (10mg MPA) was introduced once the leading follicle reached 11–12 mm, based on clinician discretion. The primary outcome was the number of mature (MII) oocytes retrieved. Secondary outcomes included duration of stimulation, total gonadotropin dose, number of clinic visits, and oocyte maturation rate.</div></div><div><h3>RESULTS</h3><div>A total of 381 cycles were analyzed. The mean age (35.92 ± 5.3 vs. 36.13 ± 5.32 years, p=0.71), AMH (0.80 ± 0.64 vs. 0.65 ± 0.61 ng/mL, p=0.12), stimulation duration (9.83 ± 1.99 vs. 9.98 ± 2.61 days, p=0.53), total gonadotropin dose (3244.81 ± 981.62 vs. 3302.31 ± 1238.68 IU, p=0.61), and estradiol and progesterone levels on trigger day were comparable between groups. The number of hospital visits was significantly lower in the fixed group (3.68 ± 0.79 vs. 4.56 ± 0.67, p&lt;0.001). The fixed group also yielded significantly more total oocytes (10.27 ± 7.35 vs. 6.26 ± 4.66, p&lt;0.001), MII oocytes (7.65 ± 5.96 vs. 4.82 ± 3.92, p&lt;0.001), MI (1.18 ± 1.41 vs. 0.61 ± 0.88, p&lt;0.001), and GV oocytes (1.41 ± 1.75 vs. 0.69 ± 1.07, p&lt;0.001). However, maturation rates (MII/total oocytes) did not differ significantly between groups.</div></div><div><h3>CONCLUSIONS</h3><div>Both fixed and flexible PPOS protocols are effective for pituitary suppression in elective fertility preservation. While the fixed approach was associated with fewer clinic visits and a higher absolute number of retrieved oocytes, oocyte maturation rates were similar. These findings support the use of fixed PPOS as a more efficient and patient-friendly option in this population.This was a retrospective study with relatively small sample size performed at a single fertility center, which may limit the generalizability of our findings.</div></div><div><h3>IMPACT STATEMENT</h3><div>Fixed PPOS yields more oocytes with similar maturation and fewer visits, supporting its use as the more practical and resource-efficient option in fertility preservation.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105325"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is the Best Strategy to Manage Women with Diminished Ovarian Reserve Using Cryopreserved Oocytes From 10 Year Follow-up?","authors":"Ece Aksakal ,&nbsp;Irem Usta Korkut ,&nbsp;Basak Balaban ,&nbsp;Bulent Urman ,&nbsp;Aylin Pelin Cil","doi":"10.1016/j.rbmo.2025.105327","DOIUrl":"10.1016/j.rbmo.2025.105327","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To evaluate the reproductive choices and outcomes of different treatment strategies in women with diminished ovarian reserve (DOR) and/or advanced age who returned to use cryopreserved oocytes.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective study included women who underwent oocyte cryopreservation (OC) between October 2014 and December 2024. Patients had AMH ≤1.3 ng/mL, ≤10 retrieved oocytes, or were aged ≥38 years. Follow-up continued through March 2025 to identify those who returned for fertility treatment. Patients who returned to use their oocytes were grouped according to their primary approach. Primary outcome was live birth rate (LBR) per patient.</div></div><div><h3>RESULTS</h3><div>Among 930 women who completed 1397 OC cycles, 55 (6%) returned. At the time of OC, the mean age (MA) was 38.7 ± 3.5 years. On average, 6.9 ± 4.3 MII were cryopreserved. Upon returning, their MA was 42.1 ± 3.6 years. As a primary approach, 32 women had oocyte thaw, 14 used both thawed and fresh oocytes in the same ART cycle (combined), 9 women had ART using fresh own oocytes and followed with either oocyte thaw (2) or combined approach (7) because none got pregnant in the first attempt. Of the 55 women 25 used only thawed oocytes (MAOC and MA thaw: 39.5 ± 3.7 and 43.7 ± 3.5, mean MII: 7 ± 4.3) and 30 used both thawed oocytes (MAOC: 37.9 ± 3.1, mean MII: 6.9 ± 4.4) and fresh oocytes (MA: 40.9 ± 3.3, mean MII: 8.6 ± 11) in total 58 oocyte thaw and 63 fresh ART cycles.</div><div>Cumulative LBR was 16% (9/55), with a 59% (13/22) miscarriage rate (MR). The pregnancy rate (PR) and LBR per patient in the thaw-only group were 36% and 20%, with a MR of 44%. In the combined group, PR and LBR from thawed oocytes were 19% and 8%, and from fresh oocytes, 31% and 8%, with MRs of 60% and 75%, respectively. Among 32 women who used only thawed oocytes, 6 achieved LB. Of 21 who used combined approach, 3 had LB (1 from thawed, 2 from fresh oocytes). No LB occurred in women who used fresh oocytes before or after using thawed oocytes.</div></div><div><h3>CONCLUSIONS</h3><div>The choice of using thawed or fresh oocytes depends largely on age at return. Advanced age and low oocyte yield are key determinants of LBR. Emphasis should be placed on cryopreserving a higher number of oocytes at younger ages. In women with limited oocytes, a combined approach may shorten time to LB and improve outcomes.</div></div><div><h3>IMPACT STATEMENT</h3><div>This is the first study to highlight the importance of managing both OC and thaw cycles in women with DOR.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105327"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Insulin Resistance and Serum Asprosin Levels in Women with Polycystic Ovary Syndrome","authors":"Oguzcan Karagoz ,&nbsp;Mert Erdemir ,&nbsp;Umit Cabus","doi":"10.1016/j.rbmo.2025.105314","DOIUrl":"10.1016/j.rbmo.2025.105314","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>The aim of this study was to evaluate the relationship between insulin resistance and serum asprosin levels in women with polycytsic ovary syndrome (PCOS) who have a normal body mass index (BMI)</div></div><div><h3>MATERIALS AND METHODS</h3><div>This study included women of reproductive age (18–38 years) who were diagnosed with PCOS. Three groups were established. PCOS patients with insulin resistance, PCOS patients without insulin resistance and healthy control patients. All participants had a BMI &lt;25 kg/m². Venous blood samples were collected on the 2nd to 5th day of menstrual cycles following a 12-hour overnight fast. The following parameters were analyzed: FSH, LH, E2, PRL, TSH, total testosterone (TT), SHBG, DHEAS, fasting blood glucose, lipid profile, insulin, HOMA-IR, and asprosin.</div></div><div><h3>RESULTS</h3><div>Significant differences were found in the LH/FSH ratio, total testosterone, free androgen index (FAI), and LDL levels between the PCOS groups and the control group. Asprosin levels were significantly higher in the normal BMI subgroup with insulin resistance (Group 1) compared to controls (p&lt;0.026). However, in the normal BMI subgroup without insulin resistance (Group 2), asprosin levels were higher than in controls but did not reach statistical significance (p=0.061). No significant difference was observed between Groups 1 and 2 (p=0.998)</div></div><div><h3>CONCLUSIONS</h3><div>Asprosin is an adipokine primarily secreted by white adipose tissue. Evidence on the relationship between PCOS and asprosin is limited. In our study, PCOS patients with normal BMI were divided into subgroups based on insulin resistance. Serum asprosin levels were significantly elevated in PCOS patients with insulin resistance compared with healthy controls. The significant correlation observed between asprosin and HOMA-IR suggests that this adipokine may be directly linked to insulin metabolism disturbances. Although asprosin levels in the non-insulin resistant PCOS group were higher than those in healthy controls, the difference didn’t reach statistical significance. This may be related to the relatively small sample size. Overall, these findings suggest that asprosin may serve as a biomarker of metabolic stress, but its elevation alone may not be sufficient to establish a direct association with PCOS. The presence of insulin resistance appears to play a key role in the clinical significance of asprosin elevation.</div></div><div><h3>IMPACT STATEMENT</h3><div>Asprosin doesn't appear to be an independent risk factor in the etiology of PCOS. Instead, it is a metabolic parameter associated with insulin resistance.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105314"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Molecular Profiling of Exosomes from First-Trimester Human Placental Organoids and Explants","authors":"Kerem Dalgic ,&nbsp;Melike Ucak ,&nbsp;Arda Inanc ,&nbsp;Gizem Melis Kargin ,&nbsp;Mert Turgal ,&nbsp;Ozgur Oktem ,&nbsp;Bora Akgun ,&nbsp;Ciler Celik Ozenci","doi":"10.1016/j.rbmo.2025.105318","DOIUrl":"10.1016/j.rbmo.2025.105318","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Exosomes are extracellular vesicles critical for intercellular communication, particularly in maternal–fetal signaling. This study aimed to isolate and characterize exosomes from human placenta organoids (HPOs) and compare their molecular profiles to those of exosomes from first-trimester placental explants.</div></div><div><h3>MATERIALS AND METHODS</h3><div>First-trimester placenta tissues (6–9 weeks; n = 9) were collected with informed consent (Ethics No:2025.107.IRB2.052). Villous explants were cultured at 24/48h in DMEM/F12+10% exosome-free FBS+1% penicillin-streptomycin, while HPOs were formed via cytotrophoblast cells embedded in Matrigel and maintained in trophoblast organoid medium (TOM). Explants were immunostained for CK7, Ki67, β-hCG, and vimentin; HPOs were evaluated via immunofluorescence (CK7, TP63, β-hCG, Ki67, E-cadherin), and β-hCG secretion was measured by ELISA. Conditioned media from explants and HPOs (day 3/8) were collected for exosome isolation by ultracentrifugation (100,000 × g, 2h, 4°C). Exosomes were analyzed by NTA, TEM, Western blot [CD63 (general), PLAP (placenta-specific), β-actin (negative) exosome markers], and RT-qPCR (miR-517a-3p, miR-519d-3p). PLAP expression in exosomes from term explants served as a positive control. Molecular fingerprints were assessed by surface-enhanced Raman spectroscopy (SERS). Statistical analysis included Mann-Whitney U test with Bonferroni correction for SERS data (p&lt; 0.001) and Kruskal-Wallis test for non-parametric NTA results (p&lt; 0.05).</div></div><div><h3>RESULTS</h3><div>Exosomes from both groups displayed characteristic morphology, marker expression, and size range (30–150 nm). Explant-derived exosomes had significantly higher particle concentrations (9.33 × 10¹⁰±8.71 × 10⁹ at 24h; 9.04 × 10¹⁰±6.72 × 10⁹ at 48h) than HPO-derived exosomes (3.19 × 10¹⁰±1.60 × 10⁹ at day 3; 3.71 × 10¹⁰±2.64 × 10⁹ at day 8) (p&lt; 0.05). CD63 was detected in exosomes for both groups; PLAP and β-actin were absent. TEM confirmed typical exosome morphology. Placenta-specific miRNAs were expressed in both groups. SERS revealed significant spectral differences (p&lt; 0.001) at 1080, 1445, and 1508 cm⁻¹, indicating differences in lipid and protein composition.</div></div><div><h3>CONCLUSIONS</h3><div>HPO-derived exosomes share key features with exosomes from matched first-trimester placenta explants, supporting the utility of HPOs as a relevant in vitro model to study placental extracellular vesicles.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study introduces HPOs as a scalable source for placenta exosome research, enabling investigation of maternal–fetal signaling and pregnancy-related disorders.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105318"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Per1 and Per2 Leads to Postnatal Growth Impairment Mimicking Fetal Growth Restriction","authors":"Begum Durkut Kuzu ,&nbsp;Yaren Sevval Yilmaz ,&nbsp;Cagla Faki ,&nbsp;Hana Asghari ,&nbsp;Derya Deniz Ozdemir ,&nbsp;Ciler Celik Ozenci","doi":"10.1016/j.rbmo.2025.105319","DOIUrl":"10.1016/j.rbmo.2025.105319","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Circadian disruption during pregnancy is clinically associated with an increased risk of fetal growth restriction; however, the underlying mechanisms remain largely unknown. To investigate the role of core circadian genes Per1 and Per2 in developmental growth, we analyzed early postnatal outcomes in a double knockout (dKO) mouse model.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Per1/Per2 dKO mouse lines were generated on a CB6F1 background using CRISPR/Cas9 genome editing, with ethical approval obtained from the institutional committee (2023.HADYEK.005). Genotyping was performed by agarose gel electrophoresis and validated through Sanger sequencing. Two experimental groups were established based on genotype: heterozygous Per1+/–/Per2+/– (dKO-het) and homozygous Per1–/–/Per2–/– (dKO-hom) breeding pairs. Gestational duration, pup number, pup body weight, and crown–rump length were recorded on postnatal days 7, 14, and 21. Data were shown as mean ± SD at each time point.</div></div><div><h3>RESULTS</h3><div>Mutant lines carried a nucleotide substitution and deletion in exon 2 of Per1, and a 19-bp deletion in exon 4 of Per2. Gestational duration was consistently 19 days across groups, and litter size was comparable between heterozygous (n=4) and homozygous dKO (n=2) breeders (6.75 ± 0.96 vs. 5.00 ± 2.83 pups per litter). However, dKO-hom pups (n=8) exhibited lower body weights compared to dKO-het pups (n=10): day 7, 4.02 ± 0.57 g vs. 4.77 ± 0.56 g (16% decrease); day 14, 6.16 ± 0.72 g vs. 8.43 ± 0.23 g (27% decrease); and day 21, 8.31 ± 0.89 g vs. 9.77 ± 0.84 g (15% decrease). Similarly, crown–rump lengths were reduced in homozygous dKO pups: day 7, 4.26 ± 0.21 cm vs. 4.37 ± 0.23 cm (3% decrease); day 14, 5.33 ± 0.22 cm vs. 6.00 ± 0.19 cm (12% decrease); and day 21, 6.05 ± 0.29 cm vs. 6.13 ± 0.27 cm (2% decrease).</div></div><div><h3>CONCLUSIONS</h3><div>We demonstrate that Per1/Per2 deficiency leads to postnatal growth impairment, despite normal gestational duration and litter size, recapitulating features of fetal growth restriction. This model provides a valuable tool for investigating the molecular mechanisms linking circadian clock disruption to developmental growth deficits.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study establishes a novel genetic model linking core circadian clock gene disruption to postnatal growth impairment, providing key mechanistic insight into how parental circadian disruption may contribute to fetal growth restriction. The Per1/Per2 double knockout mouse offers a valuable platform for investigating circadian-regulated pathways in developmental biology.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105319"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Oxygen Promotes Energy-Efficient Metabolism in Cumulus-Oocyte Complexes During IVM","authors":"Ellen Anckaert ,&nbsp;Gamze Ates ,&nbsp;Heidi Van Ranst ,&nbsp;Linde Mostinckx ,&nbsp;Wilfried Cools ,&nbsp;Ann Massie ,&nbsp;Michel De Vos ,&nbsp;Nazli Akin","doi":"10.1016/j.rbmo.2025.105291","DOIUrl":"10.1016/j.rbmo.2025.105291","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>In vitro maturation (IVM) is a mild-approach assisted reproductive technology designed to obtain mature oocytes after culturing cumulus–oocyte complexes (COCs) from 2–10 mm antral follicles. Particularly recommended for women with polycystic ovarian syndrome, IVM eliminates the risk of ovarian hyperstimulation with minimal or no gonadotropin use and abandoned ovulation trigger. Biphasic IVM culture systems are the most effective protocols with a pre-IVM phase supporting cytoplasmic maturation and oocyte competence under meiotic arrest, followed by IVM for nuclear maturation. There is currently no consensus on IVM culture oxygen settings: while in vivo COCs are exposed to low oxygen (2–9%), IVM is typically performed at atmospheric oxygen. Here we assess the effects of environmental conditions on COC energy metabolism performing pre-IVM under physiological (5%) vs atmospheric (20%) O₂.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Hyperresponder (non-PCOS) research oocyte donors (n=21) received minimal stimulation (75-150 IU menopur/day) for 0-2 days to collect COCs (n = 221) from follicles &lt;10 mm. After oocyte pick-up, COCs were randomly allocated to both atmospheric and physiological O2, for pre-IVM culture (22h). At the end of the culture, the COCs were processed to assess real-time metabolism, measure ATP concentrations, evaluate mitochondrial and antioxidative functions (CellROX, JC-1, and mBCl staining). Spent medium was analyzed for glucose and lactate. Statistical analysis was completed with a t-test or linear mixed model test.</div></div><div><h3>RESULTS</h3><div>A greater proportion of ATP was produced via mitochondrial respiration at 20% O₂ compared to 5% O₂ (43±5% vs 27±10%, p&lt;0.05). Yet, overall ATP production was greater in COCs cultured under 5% O₂ (50.3 ± 17.9 nmol/μg vs. 75.2 ± 32.7 nmol/μg, p&lt;0.05). Glucose uptake was similar between conditions, while lactate production was elevated with 5% O₂ (0.04 ± 0.03 mmol/L/COC vs 0.06 ± 0.03 mmol/L/COC, p&lt;0.05). Mitochondrial and antioxidative functions between groups were comparable.</div></div><div><h3>CONCLUSIONS</h3><div>This exploratory study shows that culturing COCs under 5% O₂ during pre-IVM leads to lower mitochondrial activity. While lacking clinical outcomes, the results support the idea that physiological conditions might be favoring an efficient energy metabolism, compared to metabolic exhaustion, possibly through lipid utilization rather than glucose.</div></div><div><h3>IMPACT STATEMENT</h3><div>Our results highlight the potential of low O2 levels to improve metabolic efficiency during IVM, encouraging re-evaluation of standard culture conditions.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105291"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of ICSI-to-Biopsy Inte rval on Embryo Ploidy Status: An Analysis of More Than 9000 Embryos.","authors":"Meral Gultomruk ,&nbsp;Fazilet Kubra Boynukalin ,&nbsp;Neslihan Sonmez ,&nbsp;Sinan Ozkavukcu ,&nbsp;Mustafa Bahceci ,&nbsp;Gurkan Bozdag","doi":"10.1016/j.rbmo.2025.105292","DOIUrl":"10.1016/j.rbmo.2025.105292","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Fertilized oocytes have the potential to develop into viable blastocysts in vitro by day5(D5), day6(D6), or day7(D7). Blastocyst expansion is key to trophectoderm biopsy (TB) success; biopsy may be ideal when herniation has begun. Due to variability expansion, TB is often delayed until optimal expansion for technical easier. However, data remain inconclusive regarding whether blastocysts with an elongated duration until TB are associated with ploidy status.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective cohort study conducted at Bahceci Health Group between January 2020-2024. The study evaluated 9.427 blastocyst stage embryos obtained from 4.616 PGT-A cycle. The interval between ICSI-TB was calculated for each embryo from software records. Time was given as hour: in(h) and minute(min). The interval has been divided into four quartiles separately for D5, and D6 embryos to evaluate the euploidy rates. Aneuploidy rates were compared across the quartiles of time between ICSI-TB. Additionally, logistic regression analysis was performed, incorporating the quartiles separately for D5, and D6 embryos to assess their impact on aneuploidy rates.</div></div><div><h3>RESULTS</h3><div>A total of 9.427 embryos were evaluated, of which 5.530(58.7%) were D5, and 3.897(41.3%) were D6 blastocyst. Euploidy rates decreased across Q1-Q4 for both D5 embryos 51.1%, 49.9%, 47.4%, 43.4% (p&lt;0.001) and 41.5%, 43.1%, 40.2%, and 33.1% (p&lt;0.001), respectively. Generalize mixed model (GMM) was used to investigate which factors affected the ploidy status of the embryo. GMM revealed that the female age[OR:0.88 CI 95%(0.87-0.89)p&lt;0.001)], embryo quality[ref:good; for poor OR:0.42 CI 95%(0.26-0.67), for moderate OR:0.58 CI 95% (0.51-0.65)p&lt;0.001], and absence of male factor[OR:1.38 CI 95%(1.03-1.84)p=0.029] were the independent determinants for D5 embryos. Female age[OR:0.86 CI 95%(0.85-0.88)p&lt;0.001), embryo quality [ref:good for poor OR:0.33 CI 95%(0.25-0.45), for moderate OR:0.48 CI 95%(0.41-0.56)p&lt;0.001], and ICSI-TB interval Q[ref:Q1, for Q2 OR:1.09 CI 95%(0.89-1.32), for Q3 OR:0.96 CI 95%(0.7-1.17), for Q4 OR:0.75 CI 95%(0.61-0.92)p=0.006] were the independent determinants for D6 embryos.</div></div><div><h3>CONCLUSIONS</h3><div>The current results suggest that, in D5 blastocysts, a longer duration from ICSI-TB does not predict ploidy status. However, within the D6 blastocyst cohort, embryos in the latest quartile exhibit the worst performance.</div></div><div><h3>IMPACT STATEMENT</h3><div>A more objective evaluation necessitates precise timing of embryo hatching, which should be assessed using morphokinetic parameters.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105292"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Homozygous c.838T>C (p.Cys280Arg) Mutation in the ZP1 (Zona Pellucida Glycoprotein 1) Gene in a Patient with EFS","authors":"Hande Nalan Tore ,&nbsp;Hasan Bulut ,&nbsp;Rovshan Jabbarov ,&nbsp;Murat Berkkanoglu ,&nbsp;Kemal Ozgur ,&nbsp;Kevin Coetzee ,&nbsp;Tarkan Kalkan","doi":"10.1016/j.rbmo.2025.105300","DOIUrl":"10.1016/j.rbmo.2025.105300","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To present a rare case of \"true\" Empty Follicle Syndrome (EFS) associated with a novel homozygous ZP1 gene mutation and to emphasize the importance of comprehensive genetic analysis in elucidating the aetiology and guiding individualized management in cases of unexplained EFS.</div></div><div><h3>MATERIALS AND METHODS</h3><div>The case is that of a 33-year-old Asian patient who presented with a 7-year history of primary infertility, with a karyotype of 46, XX,1qh+, which was considered a clinically insignificant variant. The patient’s partner presented with a normal semen analysis and a normal karyotype (46, XY). The patient’s hormone assessment on cycle day 2 of OS showed normal basal E2 (58 pg/m) and LH (0.33 IU/L) levels, and, therefore, she underwent a routine GnRH antagonist OS, starting with a daily 375 IU dose of FSH (225 IU recombinant FSH + 150 IU HMG). When leading follicles reached ∼14 mm, the antagonist was added, with FSH stimulation continuing for 11 days. A Dual trigger (0.2mg GnRH agonist plus 250 ug hCG) was administered on day 12 when leading follicles were &gt;17 mm. Follicles were collected 36 hours after trigger injection. A comprehensive genetic evaluation (LHCGR, ZP1, ZP2, ZP3, FSHR, GDF9, BMP15, PANX1) was performed using whole-exome sequencing (WES) and targeted next-generation sequencing (NGS).</div></div><div><h3>RESULTS</h3><div>At oocyte pickup (OPU), approximately 35 intact follicles were aspirated; however, no oocytes or cumulus complexes were identified despite thorough microscopic examination. Genetic analysis revealed a homozygous ZP1 c.838T&gt;C (p.Cys280Arg) mutation, classified as likely pathogenic by ACMG. This variant is predicted to impair disulfide bond formation in the zona pellucida, potentially disrupting oocyte release.</div></div><div><h3>CONCLUSIONS</h3><div>The early use of comprehensive genetic techniques is critical in encountering \"true\" EFS to guide appropriate treatment planning and set realistic expectations, thereby, enabling a personalized and rational approach to patient management.</div></div><div><h3>IMPACT STATEMENT</h3><div>This case highlights the critical role of advanced genetic testing in uncovering the underlying aetiology of true Empty Follicle Syndrome (EFS). The identification of a novel homozygous ZP1 mutation not only expands the known genetic spectrum of EFS but also underscores the importance of personalized diagnostic strategies in reproductive medicine. Early genetic evaluation can prevent repeated failed IVF attempts, guide clinical decision-making, and provide meaningful prognostic information for affected patients.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105300"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Too Many Cycles, Limited Capacity: The Impact of Daily Laboratory Workload on Embryological and Clinical Outcomes in ICSI Cycle","authors":"Havva Yesilleme ,&nbsp;Zekiye Gulfem Yurtgezen ,&nbsp;Kiper Aslan ,&nbsp;Isil Kasapoglu ,&nbsp;Gurkan Uncu ,&nbsp;Cihan Cakir","doi":"10.1016/j.rbmo.2025.105296","DOIUrl":"10.1016/j.rbmo.2025.105296","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>With the rising number of patients and increasing procedural complexity in infertility treatment, maintaining an optimal workload balance in embryology laboratories has become essential for achieving successful clinical outcomes. This study aimed to assess whether daily workload, quantified by the number of OPU procedures performed per day, affects embryological and clinical outcomes in ICSI cycles.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective study was conducted at the Bursa Uludag University ART Center between 2011 and 2025 and included 4651 ICSI cycles. Cycles involving PGD, fertility preservation, or failed oocyte retrieval were excluded. Based on the number of daily OPU procedures, cycles were categorized into three groups to reflect laboratory workload: Group 1 (1–2 OPUs/day) (n=1870) Group 2 (3–4 OPUs/day) (n=1643), and Group 3 (≥5 OPUs/day) (n=1138). Baseline patient characteristics, hormonal profiles, and ovarian stimulation parameters were compared among groups. Semen parameters and oocyte quality scores were also evaluated. Embryological and clinical outcomes were then analyzed to determine potential associations with workload intensity.</div></div><div><h3>RESULTS</h3><div>Baseline patient characteristics, hormonal profiles, ovarian stimulation data, sperm parameters, and oocyte quality scores were statistically comparable among the three groups (p &gt; 0.05). While the number of retrieved oocytes and oocyte maturation rates did not differ significantly, both fertilization (p=0.004) and blastulation rates (p=0.046) were negatively correlated with increasing laboratory workload, reaching statistical significance. However, implantation rates following fresh embryo transfers remained similar across all groups (p=0.248).</div></div><div><h3>CONCLUSIONS</h3><div>The observed decline in fertilization and blastulation rates in association with increased daily laboratory workload highlights a potential vulnerability in embryology practice under high-volume conditions. Nevertheless, the lack of significant difference in implantation rates among fresh transfers suggests that the quality of the resulting blastocyst cohort was sufficient to maintain clinical outcomes in the first transfer.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study demonstrates that elevated embryology laboratory workload is associated with reduced fertilization and blastulation efficiency, despite stable clinical and laboratory baseline conditions. Optimizing daily case volume and implementing workload management strategies may be essential for sustaining high embryological performance and ensuring consistent ART outcomes.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105296"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}