Reproductive biomedicine online最新文献

{"title":"Effect of Serum Estradiol Levels Before Progesterone Initiation on Reproductive Outcomes in HRT-FET Cycles","authors":"Gonca Ozten Dere ,&nbsp;Onur Ince ,&nbsp;Ali Can Gunes ,&nbsp;Lale Karakoc Sokmensuer ,&nbsp;Neslihan Coskun Akcay ,&nbsp;Isil Damla Dinc ,&nbsp;Fatma Caner Cabukoglu ,&nbsp;Sezcan Mumusoglu","doi":"10.1016/j.rbmo.2025.105307","DOIUrl":"10.1016/j.rbmo.2025.105307","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To determine whether serum estradiol (E2) measured before, progesterone (P) initiation influences ongoing pregnancy rate (OPR) in hormone-replacement frozen-blastocyst transfer (HRT-FET) cycles.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Retrospective cohort of the first HRT-FET cycles performed between January 2022 and March 2025 at a single IVF center. Women received oral estradiol valerate 6 mg/day for 9–18 days; serum E2 was sampled before P initiation. Embryo transfer (ET) was scheduled for day 6 of P exposure. PGT cycles were excluded. OPR was defined as the presence of fetal cardiac activity. Pregnancy loss was defined as β-hCG &gt;5 IU/L without ongoing pregnancy. Logistic regression estimated adjusted odds ratios (aORs) for OPR, controlling for age, body mass index (BMI), parity, number and grade of blastocysts transferred, and serum P4 measured on or one day prior to ET. Continuous E2 effects were modelled per 100 pg/mL increment.</div></div><div><h3>RESULTS</h3><div>A total of 209 women were included (median female age 32 years; median BMI 24.74 kg/m²). Serum E2 levels were divided into quartiles (Table 1). Crude OPR numerically increased across ascending quartiles but did not reach statistical significance (Table 1). After adjusting for confounders, the highest versus lowest E2 quartile remained non-significant (aOR 1.93 [0.78–4.74]; p = 0.153). Multivariate continuous modeling demonstrated a borderline significant positive association between serum E2 and OPR (aOR 1.33 [1.00–1.75]; p = 0.047). In contrast, higher serum E2 tended to be associated with a lower risk of pregnancy loss, although this association was not statistically significant (aOR 0.69 [0.45–1.07]; p = 0.094). Higher ET-day serum P4 (aOR 1.06 per +10 ng/mL; p = 0.002) and poor blastocyst grade (aOR 0.19 [0.06–0.55] compared to excellent grade) were independently associated with OPR, whereas female age, BMI, parity, and number of embryos transferred were not.</div></div><div><h3>CONCLUSIONS</h3><div>In HRT-FET cycles, serum E2 measured immediately before P initiation does not appear to be a robust determinant of ongoing pregnancy when analysed categorically and demonstrates only a borderline linear association after full adjustment. These findings suggest that moderate fluctuations in E2 levels before P initiation may have limited clinical relevance when luteal P administration and embryo quality are optimized.</div></div><div><h3>IMPACT STATEMENT</h3><div>Routine measurement of E2 immediately before P initiation appears to provide limited benefit in HRT-FET cycles, and its omission is unlikely to substantially impact reproductive outcomes.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105307"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532953","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":"Is There a Difference in the Success of Luteal Phase Support in Patients with Primary and Secondary Infertility?","authors":"Emine Acar ,&nbsp;Abdullah Acar ,&nbsp;Serap Mutlu Ozcelik Otcu ,&nbsp;Cigdem Kilinc","doi":"10.1016/j.rbmo.2025.105308","DOIUrl":"10.1016/j.rbmo.2025.105308","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To assess the effectiveness of luteal phase support in primary and secondary infertile women undergoing IUI.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective cohort study included 258 IUI cycles performed with CC for unexplained infertility between April 2021 and December 2024. Of these patients, 141 were primary infertile and 116 were secondary infertile. Of the primary infertile group, 69 received luteal phase support, while 72 did not. Of the secondary infertile group, 59 received luteal phase support, while 57 did not. In our clinic, we use 400 mg of natural micronized progesterone vaginally as a luteal phase support protocol.</div></div><div><h3>RESULTS</h3><div>In the primary infertile patient group, the live birth rate was significantly higher in the luteal phase support group compared to the control group (14.08% vs. 8.4%). The clinical pregnancy rate (20% vs. 8.4%) and the ongoing pregnancy rate (17.14% vs. 8.4%) were also significantly higher in the luteal phase support group. In the secondary infertile patient group, the live birth rate was significantly higher in the no luteal phase support group compared to the luteal phase support group (23.7% vs. 15.7%). The clinical pregnancy rate (28.07% vs. 16.9%) and the ongoing pregnancy rate (26.3% vs. 16.9%) were also significantly higher in the no luteal phase support group. In within-group comparisons, there were no significant differences in gestational age, mode of delivery, ectopic pregnancy rate, or abortion rate. Additionally, there were no significant differences in birth weight or birth length between the two groups.</div></div><div><h3>CONCLUSIONS</h3><div>When patients were divided into primary and secondary infertility groups in IUI cycles performed with clomiphene citrate, luteal support with vaginal progesterone significantly improved the live birth rate but did not affect neonatal outcomes. In the secondary infertility group, luteal phase support had no effect, and the live birth rate was significantly higher in the group without luteal phase support.</div></div><div><h3>IMPACT STATEMENT</h3><div>We have demonstrated with this retrospective cohort experience that further studies are needed regarding the homogeneous distribution of primary and secondary infertile patient groups in studies of luteal phase support in patients undergoing IUI due to unexplained infertility in the literature.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105308"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532954","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":"Retraction notice to: ‘Treatment of hirsutism with myo-inositol: a prospective clinical study’","authors":"M. Minozzi ,&nbsp;G D'Andrea ,&nbsp;Vittorio Unfer","doi":"10.1016/j.rbmo.2025.105271","DOIUrl":"10.1016/j.rbmo.2025.105271","url":null,"abstract":"","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 5","pages":"Article 105271"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465395","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":"Outside Back Cover - Editorial Board","authors":"","doi":"10.1016/S1472-6483(25)00557-7","DOIUrl":"10.1016/S1472-6483(25)00557-7","url":null,"abstract":"","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 5","pages":"Article 105350"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465398","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":"Can Blastocyst Formation Rate Play a Role as a Predictor of PGT-A Cycle Outcomes?","authors":"Gercek Aydin","doi":"10.1016/j.rbmo.2025.105299","DOIUrl":"10.1016/j.rbmo.2025.105299","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To investigate clinical and embryological parameters that may serve as predictors of pregnancy outcomes in preimplantation genetic testing for aneuploidy (PGT-A) cycles.</div></div><div><h3>MATERIALS AND METHODS</h3><div>A total of 98 PGT-A cycles at a private in-vitro fertilization (IVF) center between April 2022 and July 2025 were enrolled. Trophectoderm biopsy cases without any known uterine anomalies and endometrial factor are included. Ovulation induction with letrozole (n=29) or hormone replacement therapy (HRT) (n=69) were used for endometrium preparation. Clinical and embryological cycle characteristics are analysed. Blastocyst formation rate (BFR) was calculated as the number of blastocysts per MII, and the euploidy rate refers to euploid embryos per biopsied embryos. Statistical analysis included t-tests or Mann-Whitney U for continuous variables, and Chi-square test for categorical variables. To identify potential confounding factors subgroup analyses and multivariate logistic regression were performed.</div></div><div><h3>RESULTS</h3><div>Among the 98 patients, 62 (63.3%) achieved pregnancy and 36 (36.7%) did not. There were no significant differences between the groups regarding age, BMI, total gonadotropin dose, or stimulation duration. Recombinant FSH agents were the most frequently administered (n=38), followed by hMG (n=23), combination of both (n=15) and recombinant FSH+recombinant LH (n=22). Analyzing the pregnancy results, no statistically significance was observed regarding the agents used, (p&gt;0,05).</div><div>The BFR was significantly higher in the pregnant group (0.36 ± 0.28) compared to the non-pregnant group (0.27 ± 0.24, p = 0.045). The estradiol/oocyte ratio was slightly higher in the pregnant group (319 ± 180 pg/mL) than in the non-pregnant group (287 ± 148 pg/mL), although not statistically significant (p = 0.48). The euploidy rate per was 59.3% (89/150) in the pregnant group and 68.8% (66/96) in the non-pregnant group, being not statistically significant (p = 0.13). Regarding confounding factors (female or male aneuploidy, the type of gonadotropin, the type of endometrial preparation protocol), none of these demonstrated a statistically significant association with pregnancy outcome in either univariate or multivariate models.</div></div><div><h3>CONCLUSIONS</h3><div>Given our results, BFRs may predict pregnancy outcomes whereas euploidy rates do not, despite being higher in non-pregnant cases contrary to expectations.</div></div><div><h3>IMPACT STATEMENT</h3><div>BFR in PGT-A cycles may help clinicians both to counsel current patients and to shape more individualized management strategies for future cases.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105299"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532474","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":"Predictive Value of Systemic Inflammatory Index, C-Reactive Protein, and Anti-Müllerian Hormone in First Trimester Threatened","authors":"Halit Dogan ,&nbsp;Nergis Kender Erturk ,&nbsp;Anil Erturk","doi":"10.1016/j.rbmo.2025.105322","DOIUrl":"10.1016/j.rbmo.2025.105322","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Threatened miscarriage, characterized by vaginal spotting or bleeding before 20 weeks of gestation, occurs in approximately 30–40% of all pregnancies. A significant proportion of these cases result in first-trimester pregnancy loss. Despite the frequency of this presentation, there remains limited evidence to support accurate prognostication and counseling for affected women.</div><div>This study aimed to evaluate the predictive value of systemic inflammatory markers—Systemic Immune-Inflammation Index (SII), C-reactive protein (CRP), and Anti-Müllerian Hormone (AMH) — in determining pregnancy outcomes following first-trimester threatened miscarriage.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This prospective case-control study was conducted at the Gynecology and Obstetrics Clinic of a tertiary research hospital. Pregnancies &lt;12 weeks’ gestation (confirmed by crown-rump length) were included. Participants were allocated into two groups: threatened miscarriage (n = 100) and healthy controls (n = 150), matched by age and gestational age.</div><div>Complete blood count parameters (platelet, neutrophil, lymphocyte), SII (platelet × [neutrophil/lymphocyte]), CRP, and AMH levels were measured. The primary outcome was the prediction of miscarriage. Data were analyzed using SPSS 22.0 and MedCalc 18. Statistical significance was set at p &lt; 0.05.</div></div><div><h3>RESULTS</h3><div>CRP and platelet counts were significantly higher in the threatened miscarriage group than in controls (CRP: 6.9 [3.2–65] vs. 3.6 [3.1–75] mg/dL, p = 0.003; platelets: 263.1 ± 53.5 vs. 281.2 ± 61.9 × 10³/µL, p = 0.017). Among women who miscarried, CRP, SII, PLR, and platelet counts were elevated compared to ongoing pregnancies (p &lt; 0.05). Overall, CRP (9.95 [3.2–75] vs. 3.6 [3.1–11.3], p &lt; 0.001) and AMH (1.35 [0.1–11] vs. 2.2 [0.1–11], p = 0.002) differed significantly between miscarriage and non-miscarriage groups. An AMH level ≤2.1 ng/ml predicted miscarriage with 73.86% sensitivity and 50.62% specificity (p = 0.001, AUC = 0.621).</div></div><div><h3>CONCLUSIONS</h3><div>Elevated first-trimester CRP and SII levels are associated with increased risk of miscarriage in patients with threatened abortion. AMH also predicts abortion at some level. Moreover, CRP, SII, PLR, NLR, and low AMH levels may serve as independent predictive markers for early pregnancy loss, even in asymptomatic women. These parameters may facilitate early risk stratification and inform individualized follow-up strategies.</div></div><div><h3>IMPACT STATEMENT</h3><div>Anti-Müllerian hormone (AMH) levels may serve as a potential predictive biomarker for the risk of miscarriage.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105322"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532683","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":"Impact of Supraphysiological Estrogen on Endometriotic Lesion Volume During Ovarian Stimulation: A prospective Study","authors":"Ayse Seyhan Ata ,&nbsp;Irem Usta Korkut ,&nbsp;Ece Aksakal ,&nbsp;Sinem Ertas ,&nbsp;Bulent Urman","doi":"10.1016/j.rbmo.2025.105315","DOIUrl":"10.1016/j.rbmo.2025.105315","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Estrogen plays a crucial role in the progression of endometriosis, raising concerns about elevated estrogen levels during assisted reproductive technologies (ART). This study evaluates how supraphysiological estrogen concentrations during ovarian stimulation may impact the growth of endometriotic lesions, including endometriomas and deep endometriotic (DE) lesions.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This prospective study included women diagnosed with endometriosis undergoing ovarian stimulation. Three-dimensional ultrasound, combined with Virtual Organ Computer-aided Analysis (VOCAL) software, was employed for assessment. Deep endometriotic lesions were evaluated using the IDEA criteria for standardization. We compared the volumes of endometriotic nodules and endometriomas on the start day of ovarian stimulation and the trigger day of maturation.</div></div><div><h3>RESULTS</h3><div>Eleven women with 12 endometriomas and 22 deep endometriosis nodules (10 uterosacral ligament (USL) and 12 rectosigmoid (RS)) were assessed. The mean age was 36.7 ± 3.6 years, with total gonadotropin consumption averaging 3665 ± 1210 IU. The median peak estradiol level on trigger day was 1754 ng/ml, with a mean follicle count &gt;14 mm of 7.5 ± 2.7. The median number of cumulus oocyte complexes was 6, and the median number of MII oocytes was 4. The median volume of endometriomas was 19.62 cm³ (range 8 - 54.9) at the start of stimulation and 20.75 cm³ (11 - 57) on trigger day (p=0.2). For USL endometriotic nodules, median volume changed from 0.20 cm³ (0.10 - 0.66) to 0.23 cm³ (0.12 - 0.96) (p=0.18). Rectosigmoid volumes increased from 0.47 cm³ (0.14 - 1.88) to 0.60 cm³ (0.14 - 2.97) (p=0.44). No statistically significant changes were observed.</div></div><div><h3>CONCLUSIONS</h3><div>Our findings indicate that despite concerns regarding high estrogen levels worsening endometriosis, the volumes of endometriomas and deep endometriotic lesions remained stable during ovarian stimulation. The use of VOCAL software enhanced the precision of volume measurements, thereby improving the reliability of our results. However, the small sample size limits the generalizability of our conclusions. While slight increases in lesion volume were noted, these changes lacked statistical significance, implying that ovarian stimulation may not substantially affect endometriotic lesion growth in this cohort.</div></div><div><h3>IMPACT STATEMENT</h3><div>Although a slight increase in the volume of deep endometriotic nodules and endometriomas was observed, this change was not statistically significant, regardless of lesion location.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105315"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532781","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":"Do Culture Media with Different Molecular Content Change Implantation Success?","authors":"Ayse Altun Akpinar ,&nbsp;Burcin Karamustafaoglu Balci","doi":"10.1016/j.rbmo.2025.105298","DOIUrl":"10.1016/j.rbmo.2025.105298","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Embryo culture media play a crucial role in the success of in vitro fertilization. Hylauronan is the primary glycosaminoglycan found in follicular, oviductal and uterine fluids and can contribute significantly to the highly viscous environment of the female reproductive system. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays another crucial role in successful implantation, facilitating in vivo signaling, embryo development, embryo-endometrial communication, enhancing the immunological response to implantation and strengthening the ongoing pregnancy. This study aimed to evaluate whether the use of CM-GSF containing transfer media or hyaluronan-rich transfer media offers any advantages over standard conventional culture media in terms of fertilization and pregnancy outcomes.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This prospective study was conducted at Istanbul University, Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility. Twenty-one patients undergoing IVF-ET were equally distributed into three groups CM-GSF-containing transfer media (CM-GSF, CooperSurgical, Denmark), (n=7); hyaluronan-rich transfer media offers (UTM),(n=7); classical culture media (Control), (n=7), (CooperSurgical, Denmark). All groups underwent similar ovarian stimulation protocols. Demographic (age, height, weight), hormonal (FSH, LH, E2, PRL, AMH) and embryological (oocyte count, MII count, fertilization rate) data were collected.</div></div><div><h3>RESULTS</h3><div>Pregnancy rates were 28.6%(Control),42.9%(CM-GSF), and 57.1%(UTM),but did not differ significantly (p=0.048;Fisher’s for Control vs UTM).Fertilization rates were similarly high across all groups (mean 88–89%,p=0.990).No significant differences were observed in any of the baseline clinical or hormonal parameters(p &gt;0.5;Table 1).</div></div><div><h3>CONCLUSIONS</h3><div>The differences in pregnancy rates observed among the three culture media groups were statistical significance, it is noteworthy that the UTM group demonstrated a clinically higher pregnancy rate compared to CM-GSF and the control group. In clinical reproductive medicine, even modest increases in pregnancy outcomes can be highly impactful for patients, particularly in populations with diminished ovarian reserve or advanced maternal age.</div></div><div><h3>IMPACT STATEMENT</h3><div>Enriching the content of embryo transfer culture media is beneficial for achieving positive outcomes in infertility treatments. The use of hyarulinan-containing UTM media, which contributes to even a small increase in pregnancy rates, can yield positive results as a form of supportive therapy for reproductive techniques.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105298"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532864","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 AMH Levels, Hormonal Profile, and Ovulation in Women with Polycystic Ovary Syndrome","authors":"Funda Demirel","doi":"10.1016/j.rbmo.2025.105304","DOIUrl":"10.1016/j.rbmo.2025.105304","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>This study aimed to investigate the relationship between anti-Müllerian hormone (AMH) levels, hormonal profile, and ovulation in women diagnosed with polycystic ovary syndrome (PCOS), and to evaluate the effect of elevated AMH levels on ovulatory function.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This cross-sectional analytical study was conducted on 126 women who presented to a gynecology outpatient clinic of a tertiary care hospital with complaints of menstrual irregularity and were diagnosed with PCOS. Hormonal parameters, AMH levels, and ovulation status were recorded. Ovulation was determined based on serum progesterone levels and clinical follow-up (a progesterone level &gt;3 ng/mL on cycle day 21 was considered indicative of ovulation). Data were analyzed using NCSS 2020 software. The Shapiro-Wilk test was used for normality assessment. Statistical analyses included the Student’s t-test, Mann-Whitney U test, ROC curve analysis, and logistic regression. A p-value &lt;0.05 was considered statistically significant.</div></div><div><h3>RESULTS</h3><div>The mean AMH level was 6.02±2.72 ng/mL (range: 1.5–15). Ovulation was present in 25.4% (n=32) of patients and absent in 74.6% (n=94). In the comparison based on ovulatory status, LH (p=0.006), LH/FSH ratio (p=0.006), and testosterone levels (p=0.018) were significantly higher in the anovulatory group. Progesterone (p=0.001) and AMH (p=0.002) levels were significantly lower in the ovulatory group (mean AMH: 4.76±2.09 vs. 6.45±2.79 ng/mL). According to ROC analysis, the optimal AMH cut-off value to predict ovulation was 6.2 ng/mL, with 81.25% sensitivity and 46.81% specificity (AUC=0.682, p=0.001).</div></div><div><h3>CONCLUSIONS</h3><div>The findings indicate that AMH is not only a marker of ovarian reserve but may also be a predictor of ovulatory function in women with PCOS. Elevated AMH levels are associated with increased LH and testosterone levels and decreased ovulation rates. This may reflect a folliculogenesis arrest at the antral stage. In women with PCOS, elevated AMH levels are significantly associated with anovulation and hyperandrogenism. AMH should be considered not only as an indicator of ovarian reserve but also as a marker of functional status in this population. Clinically, women with AMH levels ≥6.2 ng/mL should be closely monitored for ovulatory dysfunction and managed with individualized treatment strategies.</div></div><div><h3>IMPACT STATEMENT</h3><div>This suggests that excessively high AMH levels may function as a marker of ovarian dysfunction rather than reproductive potential.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105304"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532950","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":"Altered Molecular Clock and Steroidogenic Gene Rhythmicity In DHT-Induced PCOS Model of Human Granulosa Cells","authors":"Hana Asghari ,&nbsp;Begum Durkut Kuzu ,&nbsp;Seden Nadire Harputluoglu Efendi ,&nbsp;Ibrahim Halil Kavakli ,&nbsp;Ciler Celik-Ozenci","doi":"10.1016/j.rbmo.2025.105312","DOIUrl":"10.1016/j.rbmo.2025.105312","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To investigate the rhythmic expression of molecular clock genes and steroidogenic enzymes in human granulosa cells and an in vitro PCOS model.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Human granulosa cell line (KGN) was used as control, and 25 nM dihydrotestosterone (DHT)-treated KGN cells served as the in vitro PCOS model. Cell viability under DHT treatment was confirmed by MTT assay. PCOS induction was validated by elevated AMH and decreased CYP19A1 mRNA expression. BMAL1 oscillation was monitored in both groups over 7 days using a pLenti-BMAL1-DLuc reporter and the Lumicycle system. Rhythmicity was analyzed using JTK_Cycle, a non-parametric algorithm. Both groups were synchronized with dexamethasone and sampled every 6 hours over a 24-hour Zeitgeber time (ZT) course to assess the temporal expression of clock genes (BMAL1, CLOCK, PER1/2/3, CRY1/2) and steroidogenic enzymes (CYP19A1, StAR) via qPCR and Western blotting. Statistical significance was determined by two-way ANOVA, Mann-Whitney and Kruskal–Wallis tests (p &lt; 0.05).</div></div><div><h3>RESULTS</h3><div>In control cells, BMAL1 exhibited robust rhythmicity (23.33 h period, 735 counts/sec amplitude). BMAL1 mRNA peaked at ZT12; protein levels peaked at ZT6, 18, and 24. CLOCK, PER1/2/3, and CRY1/2 showed rhythmic mRNA expression. CYP19A1 and StAR also exhibited significant mRNA rhythmicity, peaking at ZT6. CYP19A1 protein increased from ZT6 to ZT24, while StAR protein peaked at ZT6 and ZT18. In the PCOS cells, BMAL1 rhythmicity was disrupted, with a prolonged period (24.17 h) and reduced amplitude (507 counts/sec). BMAL1 mRNA was significantly downregulated and lost cyclicity, particularly at ZT6 (p&lt;0.0286). CLOCK, PERs, and CRYs also lost rhythmic expression. CYP19A1 mRNA expression exhibited no significant circadian variation; however, protein levels peaked at ZT6 and were lowest in the control group (p &lt; 0.0076). StAR mRNA was reduced at ZT18; protein levels were significantly decreased at ZT18 (p&lt;0.0001).</div></div><div><h3>CONCLUSIONS</h3><div>Human granulosa cells display robust circadian rhythmicity, marked by BMAL1 oscillation. DHT-induced PCOS disrupts these rhythms, indicating that androgen excess impairs ovarian clock function and alters steroidogenic pathways.</div></div><div><h3>IMPACT STATEMENT</h3><div>DHT-induced circadian disruption in granulosa cells highlights the role of temporal regulation in PCOS pathophysiology and supports chronotherapeutic strategies to restore ovarian function.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105312"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532388","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}