Jun Woo Kim, Sooyoung Jeong, Jinkyung Ko, Jiyoung Ann, Chang-Young Hur, Jin-Ho Lim
Objective: This study aimed to determine the optimal timing of cryopreservation and biopsy procedures in preimplantation genetic testing for aneuploidy (PGT-A) by comparing clinical outcomes between fresh embryo biopsy (fresh biopsy) and frozen-thawed embryo biopsy (frozen biopsy) procedures in high-risk patients.
Methods: This retrospective study included 844 patients undergoing 844 cycles conducted from August 2019 to December 2023. PGT-A was performed via trophectoderm biopsy using array comparative genomic hybridization and next-generation sequencing for comprehensive 24-chromosome screening. Patients were divided into two groups based on biopsy timing: fresh embryo biopsy (531 patients) and frozen- thawed embryo biopsy (313 patients).
Results: The clinical pregnancy rate was significantly higher in the fresh biopsy group compared to the frozen biopsy group (58.7% vs. 45.6%; odds ratio [OR], 1.695; 95% confidence interval [CI], 1.215 to 2.364; p=0.002). Furthermore, the fresh biopsy group showed higher implantation rates (45.6% vs. 32.1%; OR, 1.767; 95% CI, 1.274 to 2.451; p=0.002), ongoing pregnancy or live birth rates per cycle (48.0% vs. 35.8%; OR, 1.652; 95% CI, 1.177 to 2.319; p=0.004), and rates of good-quality blastocysts (57.1% vs. 32.1%, p<0.001) compared with the frozen biopsy group. Miscarriage rates did not differ significantly between the groups (18.2% vs. 21.4%; OR, 0.818; 95% CI, 0.457 to 1.465; p=0.501).
Conclusion: Fresh biopsy demonstrated superior clinical outcomes compared with frozen biopsy, likely due to better embryo quality. Both fresh and frozen biopsies remain viable options for PGT-A, with frozen biopsy serving as a practical alternative. Embryo quality and euploid status continue to be critical considerations for embryo transfer selection.
目的:本研究旨在通过比较高风险患者新鲜胚胎活检(fresh biopsy)和冻融胚胎活检(frozen biopsy)的临床结果,确定非整倍体植入前基因检测(PGT-A)中冷冻保存和活检的最佳时机。方法:本回顾性研究纳入844例患者,于2019年8月至2023年12月进行844次周期。PGT-A通过滋养外胚层活检进行,采用阵列比较基因组杂交和下一代测序进行全面的24染色体筛选。根据活检时间将患者分为两组:新鲜胚胎活检(531例)和冻融胚胎活检(313例)。结果:新鲜活检组临床妊娠率明显高于冷冻活检组(58.7% vs. 45.6%;优势比[OR], 1.695; 95%可信区间[CI], 1.215 ~ 2.364; p=0.002)。此外,新鲜活检组表现出更高的着床率(45.6% vs. 32.1%; OR, 1.767; 95% CI, 1.274 ~ 2.451; p=0.002)、每个周期的妊娠或活产率(48.0% vs. 35.8%; OR, 1.652; 95% CI, 1.177 ~ 2.319; p=0.004)和优质囊胚率(57.1% vs. 32.1%)。结论:新鲜活检与冷冻活检相比表现出更好的临床结果,可能是由于胚胎质量更好。新鲜活检和冷冻活检都是PGT-A的可行选择,冷冻活检是一种实用的选择。胚胎质量和整倍体状态仍然是胚胎移植选择的关键考虑因素。
{"title":"Impact of cryopreservation and biopsy procedure timing on clinical outcomes in high-risk patients.","authors":"Jun Woo Kim, Sooyoung Jeong, Jinkyung Ko, Jiyoung Ann, Chang-Young Hur, Jin-Ho Lim","doi":"10.5653/cerm.2025.07850","DOIUrl":"https://doi.org/10.5653/cerm.2025.07850","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the optimal timing of cryopreservation and biopsy procedures in preimplantation genetic testing for aneuploidy (PGT-A) by comparing clinical outcomes between fresh embryo biopsy (fresh biopsy) and frozen-thawed embryo biopsy (frozen biopsy) procedures in high-risk patients.</p><p><strong>Methods: </strong>This retrospective study included 844 patients undergoing 844 cycles conducted from August 2019 to December 2023. PGT-A was performed via trophectoderm biopsy using array comparative genomic hybridization and next-generation sequencing for comprehensive 24-chromosome screening. Patients were divided into two groups based on biopsy timing: fresh embryo biopsy (531 patients) and frozen- thawed embryo biopsy (313 patients).</p><p><strong>Results: </strong>The clinical pregnancy rate was significantly higher in the fresh biopsy group compared to the frozen biopsy group (58.7% vs. 45.6%; odds ratio [OR], 1.695; 95% confidence interval [CI], 1.215 to 2.364; p=0.002). Furthermore, the fresh biopsy group showed higher implantation rates (45.6% vs. 32.1%; OR, 1.767; 95% CI, 1.274 to 2.451; p=0.002), ongoing pregnancy or live birth rates per cycle (48.0% vs. 35.8%; OR, 1.652; 95% CI, 1.177 to 2.319; p=0.004), and rates of good-quality blastocysts (57.1% vs. 32.1%, p<0.001) compared with the frozen biopsy group. Miscarriage rates did not differ significantly between the groups (18.2% vs. 21.4%; OR, 0.818; 95% CI, 0.457 to 1.465; p=0.501).</p><p><strong>Conclusion: </strong>Fresh biopsy demonstrated superior clinical outcomes compared with frozen biopsy, likely due to better embryo quality. Both fresh and frozen biopsies remain viable options for PGT-A, with frozen biopsy serving as a practical alternative. Embryo quality and euploid status continue to be critical considerations for embryo transfer selection.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyung Min Kim, Jin Heo, Hyoeun Kang, Kyungmi Juhn, Eunhye Jung, Hyejeong Park, Juhee Jin, Jinho Lim, Hye Jun Lee, Jeong Yoon
Objective: This study aimed to establish a quantitative and interpretable method for assessing oocyte quality by analyzing cytoplasmic morphology and intensity features using artificial intelligence.
Methods: A total of 695 oocyte images were collected from hormonally stimulated young and aged mice. The cytoplasmic region was manually annotated to exclude polar bodies, and radiomics analysis was performed to extract morphological and intensity-based features.
Results: Clustering with a Gaussian mixture model identified three distinct oocyte subtypes with unique cytoplasmic characteristics. Cluster 2, with the most spherical and compact oocytes, demonstrated the highest blastocyst formation rate (42.9%), followed by clusters 3 (35.3%) and 1 (20.4%). Cluster 2 oocytes also showed the highest mean intensity and lowest variability, suggesting uniform cytoplasmic structure. Notably, some aged oocytes in cluster 2 exhibited developmental potential comparable to that of young mice, indicating that cytoplasmic quality may be a more informative predictor than age alone.
Conclusion: These findings underscore the value of cytoplasmic features as objective indicators of developmental competence. This artificial intelligence-driven approach may improve embryo selection by providing a standardized, non-invasive method for evaluating oocytes, ultimately contributing to enhanced clinical outcomes in assisted reproductive technologies.
{"title":"Artificial intelligence-powered oocyte evaluation: Correlating cytoplasmic features with blastocyst development.","authors":"Hyung Min Kim, Jin Heo, Hyoeun Kang, Kyungmi Juhn, Eunhye Jung, Hyejeong Park, Juhee Jin, Jinho Lim, Hye Jun Lee, Jeong Yoon","doi":"10.5653/cerm.2025.08396","DOIUrl":"https://doi.org/10.5653/cerm.2025.08396","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to establish a quantitative and interpretable method for assessing oocyte quality by analyzing cytoplasmic morphology and intensity features using artificial intelligence.</p><p><strong>Methods: </strong>A total of 695 oocyte images were collected from hormonally stimulated young and aged mice. The cytoplasmic region was manually annotated to exclude polar bodies, and radiomics analysis was performed to extract morphological and intensity-based features.</p><p><strong>Results: </strong>Clustering with a Gaussian mixture model identified three distinct oocyte subtypes with unique cytoplasmic characteristics. Cluster 2, with the most spherical and compact oocytes, demonstrated the highest blastocyst formation rate (42.9%), followed by clusters 3 (35.3%) and 1 (20.4%). Cluster 2 oocytes also showed the highest mean intensity and lowest variability, suggesting uniform cytoplasmic structure. Notably, some aged oocytes in cluster 2 exhibited developmental potential comparable to that of young mice, indicating that cytoplasmic quality may be a more informative predictor than age alone.</p><p><strong>Conclusion: </strong>These findings underscore the value of cytoplasmic features as objective indicators of developmental competence. This artificial intelligence-driven approach may improve embryo selection by providing a standardized, non-invasive method for evaluating oocytes, ultimately contributing to enhanced clinical outcomes in assisted reproductive technologies.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-22DOI: 10.5653/cerm.2025.07892
Seul Ki Kim, Byung Chul Jee
Objective: This study aimed to determine whether pre-treatment with everolimus or rapamycin could prevent ovarian follicle damage induced by cyclophosphamide (Cp).
Methods: A total of 120 female BDF-1 mice were randomly assigned into four groups receiving specific treatments. The control group received normal saline on days 1, 3, 5, and 13. The Cp group received saline on days 1, 3, and 5, followed by Cp administration on day 13. The everolimus+Cp group was given everolimus on days 1, 3, and 5, then Cp on day 13. Similarly, the rapamycin+Cp group received rapamycin on days 1, 3, and 5, followed by Cp on day 13. On day 20, all mice were euthanized, ovaries were harvested for histological analysis, and protein expression levels of B-cell lymphoma-extra large (BCL-xL), caspase 3, and mammalian target of rapamycin were evaluated by Western blot analysis.
Results: The number of primordial follicles was lower in the Cp group than in the control group. The everolimus group and the rapamycin group also showed reduced primordial follicle counts. No significant differences were observed in the proportions of G1 primordial or G1 secondary follicles among the groups. Compared to the control group, the Cp group and the everolimus group showed lower proportions of G1 primary follicles. However, the rapamycin group had a G1 primary follicle proportion similar to that of the control group. The Cp, everolimus, and rapamycin groups exhibited lower proportions of G1 antral follicles than the control group.
Conclusion: Pre-treatment with rapamycin preserved the proportion of G1 primary follicles; however, neither everolimus nor rapamycin preserved the primordial follicle counts.
{"title":"The role of mammalian target of rapamycin inhibitors in mitigating cyclophosphamide-induced ovarian damage in a murine model.","authors":"Seul Ki Kim, Byung Chul Jee","doi":"10.5653/cerm.2025.07892","DOIUrl":"10.5653/cerm.2025.07892","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine whether pre-treatment with everolimus or rapamycin could prevent ovarian follicle damage induced by cyclophosphamide (Cp).</p><p><strong>Methods: </strong>A total of 120 female BDF-1 mice were randomly assigned into four groups receiving specific treatments. The control group received normal saline on days 1, 3, 5, and 13. The Cp group received saline on days 1, 3, and 5, followed by Cp administration on day 13. The everolimus+Cp group was given everolimus on days 1, 3, and 5, then Cp on day 13. Similarly, the rapamycin+Cp group received rapamycin on days 1, 3, and 5, followed by Cp on day 13. On day 20, all mice were euthanized, ovaries were harvested for histological analysis, and protein expression levels of B-cell lymphoma-extra large (BCL-xL), caspase 3, and mammalian target of rapamycin were evaluated by Western blot analysis.</p><p><strong>Results: </strong>The number of primordial follicles was lower in the Cp group than in the control group. The everolimus group and the rapamycin group also showed reduced primordial follicle counts. No significant differences were observed in the proportions of G1 primordial or G1 secondary follicles among the groups. Compared to the control group, the Cp group and the everolimus group showed lower proportions of G1 primary follicles. However, the rapamycin group had a G1 primary follicle proportion similar to that of the control group. The Cp, everolimus, and rapamycin groups exhibited lower proportions of G1 antral follicles than the control group.</p><p><strong>Conclusion: </strong>Pre-treatment with rapamycin preserved the proportion of G1 primary follicles; however, neither everolimus nor rapamycin preserved the primordial follicle counts.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"359-366"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144973693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-27DOI: 10.5653/cerm.2024.07388
Md Shahed Morshed, Hurjahan Banu, Md Shamim Hossan, Hafsa Mahrukh, Muhammad Abul Hasanat
Objective: We compared various adiposity indices (AIs)-body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI), lipid accumulation product, and the triglyceride-glucose (TyG), TyG-BMI, and TyG-WC indices-regarding their associations with insulin resistance (IR) among women with polycystic ovary syndrome (PCOS).
Methods: This cross-sectional investigation included 632 reproductive-aged women with PCOS, aligning with the 2018 International Evidence-based Guideline. Clinical characteristics, including height, weight, and WC, were recorded. Fasting blood samples were analyzed to measure insulin, lipid, and glucose levels. AIs were then calculated using these measurements along with various formulas. The homeostatic model assessment for IR was utilized, with a value of 2.6 or higher indicating IR. An area under the curve (AUC) above 0.8 was considered clinically useful.
Results: Approximately 69.1% of participants exhibited IR. All AIs were significant predictors of IR, regardless of androgen status. VAI and the TyG index were identified as poor markers of IR among women with PCOS (AUC, 0.6 to 0.69), while the remaining indices were considered fair markers (AUC, 0.7 to 0.79). VAI underperformed all other AIs except the TyG index, which was notably inferior to the TyG-BMI and TyG-WC indices. Nevertheless, the AUCs of TyG-BMI and TyG-WC were similar to those of BMI and WC.
Conclusion: Although AIs exhibit androgen-independent relationships with IR, their usefulness as indicators of IR in PCOS is not adequately supported by our results (AUC <0.8). Furthermore, combining the TyG index with BMI and WC does not significantly improve the diagnostic utility of IR.
{"title":"Association of adiposity indices with insulin resistance among women with polycystic ovary syndrome.","authors":"Md Shahed Morshed, Hurjahan Banu, Md Shamim Hossan, Hafsa Mahrukh, Muhammad Abul Hasanat","doi":"10.5653/cerm.2024.07388","DOIUrl":"10.5653/cerm.2024.07388","url":null,"abstract":"<p><strong>Objective: </strong>We compared various adiposity indices (AIs)-body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI), lipid accumulation product, and the triglyceride-glucose (TyG), TyG-BMI, and TyG-WC indices-regarding their associations with insulin resistance (IR) among women with polycystic ovary syndrome (PCOS).</p><p><strong>Methods: </strong>This cross-sectional investigation included 632 reproductive-aged women with PCOS, aligning with the 2018 International Evidence-based Guideline. Clinical characteristics, including height, weight, and WC, were recorded. Fasting blood samples were analyzed to measure insulin, lipid, and glucose levels. AIs were then calculated using these measurements along with various formulas. The homeostatic model assessment for IR was utilized, with a value of 2.6 or higher indicating IR. An area under the curve (AUC) above 0.8 was considered clinically useful.</p><p><strong>Results: </strong>Approximately 69.1% of participants exhibited IR. All AIs were significant predictors of IR, regardless of androgen status. VAI and the TyG index were identified as poor markers of IR among women with PCOS (AUC, 0.6 to 0.69), while the remaining indices were considered fair markers (AUC, 0.7 to 0.79). VAI underperformed all other AIs except the TyG index, which was notably inferior to the TyG-BMI and TyG-WC indices. Nevertheless, the AUCs of TyG-BMI and TyG-WC were similar to those of BMI and WC.</p><p><strong>Conclusion: </strong>Although AIs exhibit androgen-independent relationships with IR, their usefulness as indicators of IR in PCOS is not adequately supported by our results (AUC <0.8). Furthermore, combining the TyG index with BMI and WC does not significantly improve the diagnostic utility of IR.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":"52 4","pages":"342-347"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-03-21DOI: 10.5653/cerm.2024.07402
Aamir Javed, Sanaz A Movassagh, Shilpa Doultani, Tulsi Kumari, Rishish Sharma, Md Kashif Zeya, Syed Waseem Andrabi, Kamal Saba
The importance of maintaining adequate levels of vitamin D for optimal male sexual health is highlighted by recent evidence suggesting a link between vitamin D insufficiency and erectile dysfunction (ED). This review examines current research that indicates an association between decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D), specifically levels below 20 ng/mL, and a higher prevalence of ED, including severe cases. Studies have shown a significant correlation between a decrease of 10 ng/mL in 25(OH)D levels and a 12% increase in the prevalence of ED. The active form of vitamin D, calcitriol, facilitates the synthesis of nitric oxide, a potent vasodilator crucial for penile erection. Additionally, vitamin D supplementation has been shown to improve erectile function by enhancing endothelial vasodilation and arterial blood flow. It is essential to maintain serum 25(OH)D levels within the recommended range of 20 to 50 ng/mL, given the connection between vascular disorders and ED. A comprehensive approach, including dietary changes, consistent physical activity, and lifestyle modifications, is necessary to prevent ED. While vitamin D deficiency may contribute to ED, it is crucial to recognize that ED is multifactorial and should be addressed by considering all underlying causes. Individuals consistently experiencing symptoms of ED are advised to consult healthcare professionals for appropriate therapeutic interventions. This review emphasizes the importance of considering serum vitamin D levels when assessing male sexual health and calls for further research to clarify the role of vitamin D in the etiology and treatment of ED.
最近有证据表明,维生素 D 不足与勃起功能障碍(ED)之间存在联系,这凸显了维持充足的维生素 D 水平对男性最佳性健康的重要性。本综述探讨了当前的研究,这些研究表明血清中 25- 羟基维生素 D(25(OH)D)浓度的降低,特别是低于 20 纳克/毫升的水平,与较高的 ED 患病率(包括严重病例)之间存在关联。研究表明,25(OH)D 水平每降低 10 纳克/毫升,ED 患病率就会增加 12%,两者之间存在明显的相关性。维生素 D 的活性形式--钙三醇能促进一氧化氮的合成,而一氧化氮是一种对阴茎勃起至关重要的强效血管扩张剂。此外,补充维生素 D 还能增强内皮血管扩张和动脉血流,从而改善勃起功能。鉴于血管疾病与 ED 之间的联系,将血清 25(OH)D 水平保持在 20 至 50 纳克/毫升的推荐范围内至关重要。预防 ED 需要采取综合措施,包括改变饮食习惯、坚持体育锻炼和改变生活方式。虽然维生素 D 缺乏可能是导致 ED 的原因之一,但必须认识到 ED 是由多种因素造成的,因此应通过考虑所有潜在原因来解决这一问题。建议持续出现 ED 症状的患者咨询医疗保健专业人员,以采取适当的治疗干预措施。本综述强调了在评估男性性健康时考虑血清维生素 D 水平的重要性,并呼吁开展进一步研究,以明确维生素 D 在 ED 病因学和治疗中的作用。
{"title":"The relationship between vitamin D levels and erectile dysfunction: A mini-review.","authors":"Aamir Javed, Sanaz A Movassagh, Shilpa Doultani, Tulsi Kumari, Rishish Sharma, Md Kashif Zeya, Syed Waseem Andrabi, Kamal Saba","doi":"10.5653/cerm.2024.07402","DOIUrl":"10.5653/cerm.2024.07402","url":null,"abstract":"<p><p>The importance of maintaining adequate levels of vitamin D for optimal male sexual health is highlighted by recent evidence suggesting a link between vitamin D insufficiency and erectile dysfunction (ED). This review examines current research that indicates an association between decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D), specifically levels below 20 ng/mL, and a higher prevalence of ED, including severe cases. Studies have shown a significant correlation between a decrease of 10 ng/mL in 25(OH)D levels and a 12% increase in the prevalence of ED. The active form of vitamin D, calcitriol, facilitates the synthesis of nitric oxide, a potent vasodilator crucial for penile erection. Additionally, vitamin D supplementation has been shown to improve erectile function by enhancing endothelial vasodilation and arterial blood flow. It is essential to maintain serum 25(OH)D levels within the recommended range of 20 to 50 ng/mL, given the connection between vascular disorders and ED. A comprehensive approach, including dietary changes, consistent physical activity, and lifestyle modifications, is necessary to prevent ED. While vitamin D deficiency may contribute to ED, it is crucial to recognize that ED is multifactorial and should be addressed by considering all underlying causes. Individuals consistently experiencing symptoms of ED are advised to consult healthcare professionals for appropriate therapeutic interventions. This review emphasizes the importance of considering serum vitamin D levels when assessing male sexual health and calls for further research to clarify the role of vitamin D in the etiology and treatment of ED.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"334-341"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-22DOI: 10.5653/cerm.2024.07374
Amir Abdolmaleki, Hadis Amirsayyafi, Saeed Khazaiel, Cyrus Jalili, Kamran Mansourhi, Mitra Bakhtiari
Objective: Endometriosis (Endo) involves inflammation and angiogenesis within lesions, potentially causing embryo implantation failure. Paeonia lactiflora (PL) root exhibits anti-angiogenic and anti-inflammatory properties. This experiment investigated the therapeutic effects of PL on endometriotic lesion atrophy and embryo implantation following in vitro fertilization (IVF).
Methods: Female mice (n=32) were allocated into treatment and sham groups. Endo was induced through xenograft transplantation of rat endometrium to anterior abdominal walls of recipient (Endo) mice. PL root was extracted, phytochemically characterized, and orally administered (1.06 mg PL/20 g mouse) for 17 consecutive days. Through IVF, cultured mouse embryos were implanted into Endo mouse uteri. Ten days post-IVF, samples were collected, including intra-abdominal fluid for measurement of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α) using enzyme-linked immunosorbent assay. Embryo-containing uteri underwent trypan blue staining, while uterus fragments were stained with hematoxylin and eosin and analyzed for leukemia inhibitory factor (LIF) gene expression using quantitative polymerase chain reaction. The number of embryo implantation sites and diameter of endometriotic lesions were recorded. Data were analyzed using SPSS ver. 19, with p-values <0.05 considered to indicate statistical significance.
Results: Following Endo induction, TNF-α and VEGF levels and lesion diameter increased (p<0.05). LIF gene expression and embryo implantation rate decreased (p<0.05). After PL extract administration to Endo mice, TNF-α levels, VEGF levels, and lesion diameter decreased (p<0.05), while LIF gene expression and implantation rate increased (p<0.05).
Conclusion: PL extract (1.06 mg/20 g mouse) decreases TNF-α and VEGF levels, suppressing inflammation and angiogenesis and causing endometriotic lesion atrophy. Furthermore, PL increases uterine LIF gene expression, promoting successful implantation post-IVF in Endo mice.
{"title":"Formulation of Paeonia lactiflora root extract can induce atrophy of endometriotic lesions and accelerate embryo implantation following in vitro fertilization in endometriosis: An experimental study.","authors":"Amir Abdolmaleki, Hadis Amirsayyafi, Saeed Khazaiel, Cyrus Jalili, Kamran Mansourhi, Mitra Bakhtiari","doi":"10.5653/cerm.2024.07374","DOIUrl":"10.5653/cerm.2024.07374","url":null,"abstract":"<p><strong>Objective: </strong>Endometriosis (Endo) involves inflammation and angiogenesis within lesions, potentially causing embryo implantation failure. Paeonia lactiflora (PL) root exhibits anti-angiogenic and anti-inflammatory properties. This experiment investigated the therapeutic effects of PL on endometriotic lesion atrophy and embryo implantation following in vitro fertilization (IVF).</p><p><strong>Methods: </strong>Female mice (n=32) were allocated into treatment and sham groups. Endo was induced through xenograft transplantation of rat endometrium to anterior abdominal walls of recipient (Endo) mice. PL root was extracted, phytochemically characterized, and orally administered (1.06 mg PL/20 g mouse) for 17 consecutive days. Through IVF, cultured mouse embryos were implanted into Endo mouse uteri. Ten days post-IVF, samples were collected, including intra-abdominal fluid for measurement of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α) using enzyme-linked immunosorbent assay. Embryo-containing uteri underwent trypan blue staining, while uterus fragments were stained with hematoxylin and eosin and analyzed for leukemia inhibitory factor (LIF) gene expression using quantitative polymerase chain reaction. The number of embryo implantation sites and diameter of endometriotic lesions were recorded. Data were analyzed using SPSS ver. 19, with p-values <0.05 considered to indicate statistical significance.</p><p><strong>Results: </strong>Following Endo induction, TNF-α and VEGF levels and lesion diameter increased (p<0.05). LIF gene expression and embryo implantation rate decreased (p<0.05). After PL extract administration to Endo mice, TNF-α levels, VEGF levels, and lesion diameter decreased (p<0.05), while LIF gene expression and implantation rate increased (p<0.05).</p><p><strong>Conclusion: </strong>PL extract (1.06 mg/20 g mouse) decreases TNF-α and VEGF levels, suppressing inflammation and angiogenesis and causing endometriotic lesion atrophy. Furthermore, PL increases uterine LIF gene expression, promoting successful implantation post-IVF in Endo mice.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"348-358"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-05-20DOI: 10.5653/cerm.2024.07668
Maroua Ben Rhouma, Hatem Bahri, Mustapha Ben Khalifa, Mohsen Sakly, Khémais Ben Rhouma, Moncef Benkhalifa, Olfa Tebourbi
Objective: This study investigated oxidative stress and its impact on sperm quality in men with infertility, focusing on lipid peroxidation and the activity of antioxidant enzymes-catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)-in seminal fluid.
Methods: This study was conducted from January 2021 to January 2023 and involved 163 male patients who had been experiencing infertility for over a year. The participants were categorized according to semen quality. Semen samples were analyzed for sperm concentration, motility, and morphology following the World Health Organization guidelines. Oxidative stress was evaluated by measuring levels of malondialdehyde (MDA), an indicator of lipid peroxidation, as well as the activity of CAT, SOD, and GPx. Ethical approval and informed consent were obtained from all participants.
Results: Semen quality and oxidative stress were evaluated in cases of male infertility, with patients categorized into five groups: normozoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and oligo-astheno-teratozoospermia. The pathological groups exhibited significant reductions in sperm count, motility, and morphology. Additionally, lipid peroxidation, as shown by increased MDA levels, was significantly elevated in all pathological groups. The activities of CAT, SOD, and GPx were significantly diminished in these groups, with the most substantial declines noted in the oligo-astheno-teratozoospermia group.
Conclusion: Oxidative stress, indicated by elevated MDA levels, was correlated with poor sperm quality. The decreased activity of antioxidant enzymes in pathological semen implies that a weakened antioxidant defense contributes to sperm dysfunction. These findings suggest that antioxidant interventions could improve sperm quality in men experiencing infertility, though additional research is required.
{"title":"Oxidative stress and its correlation with sperm parameters in different semen quality groups.","authors":"Maroua Ben Rhouma, Hatem Bahri, Mustapha Ben Khalifa, Mohsen Sakly, Khémais Ben Rhouma, Moncef Benkhalifa, Olfa Tebourbi","doi":"10.5653/cerm.2024.07668","DOIUrl":"10.5653/cerm.2024.07668","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated oxidative stress and its impact on sperm quality in men with infertility, focusing on lipid peroxidation and the activity of antioxidant enzymes-catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)-in seminal fluid.</p><p><strong>Methods: </strong>This study was conducted from January 2021 to January 2023 and involved 163 male patients who had been experiencing infertility for over a year. The participants were categorized according to semen quality. Semen samples were analyzed for sperm concentration, motility, and morphology following the World Health Organization guidelines. Oxidative stress was evaluated by measuring levels of malondialdehyde (MDA), an indicator of lipid peroxidation, as well as the activity of CAT, SOD, and GPx. Ethical approval and informed consent were obtained from all participants.</p><p><strong>Results: </strong>Semen quality and oxidative stress were evaluated in cases of male infertility, with patients categorized into five groups: normozoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and oligo-astheno-teratozoospermia. The pathological groups exhibited significant reductions in sperm count, motility, and morphology. Additionally, lipid peroxidation, as shown by increased MDA levels, was significantly elevated in all pathological groups. The activities of CAT, SOD, and GPx were significantly diminished in these groups, with the most substantial declines noted in the oligo-astheno-teratozoospermia group.</p><p><strong>Conclusion: </strong>Oxidative stress, indicated by elevated MDA levels, was correlated with poor sperm quality. The decreased activity of antioxidant enzymes in pathological semen implies that a weakened antioxidant defense contributes to sperm dysfunction. These findings suggest that antioxidant interventions could improve sperm quality in men experiencing infertility, though additional research is required.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"386-393"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-24DOI: 10.5653/cerm.2025.08228
Chang-Seop Hyun, Mi-Ji Park, Eun-Jeong Jang, An-Na Kim, Seong-Ho Yang, Yong-Soo Hur, Yeong-Je Gang, Jin-Ho Lim
Objective: In this study, we investigated whether adding autologous platelet-rich plasma (PRP) to the culture medium affects embryo development and clinical outcomes in patients with recurrent implantation failure (RIF).
Methods: This study included 201 patients with previous RIF. Of these, 77 opted to receive the treatment and were assigned to the PRP group, and 124 declined and were assigned to the control group. In the PRP group, normally fertilized embryos were cultured in medium supplemented with 5% PRP, whereas embryos in the control group were cultured without PRP. Embryo transfer was performed on day 3 after evaluation of embryo quality. A comparative analysis was then conducted between the two groups, focusing on embryo quality and clinical outcomes.
Results: Although no significant differences were observed in fertilization or cleavage rates, the PRP group had a significantly higher proportion of good-quality embryos with at least six cells on day 3 than the control group. The clinical pregnancy and implantation rates in the PRP group were also significantly higher than those in the control group. Furthermore, the ongoing pregnancy rate was notably higher in the PRP group, and successful live births were achieved. Miscarriage rates were similar between groups.
Conclusion: Incorporating PRP as an additive into the culture medium improved embryo quality and increased implantation, clinical pregnancy, and ongoing pregnancy rates.
{"title":"Effects of platelet-rich plasma as a new additive on human embryo development and clinical outcomes.","authors":"Chang-Seop Hyun, Mi-Ji Park, Eun-Jeong Jang, An-Na Kim, Seong-Ho Yang, Yong-Soo Hur, Yeong-Je Gang, Jin-Ho Lim","doi":"10.5653/cerm.2025.08228","DOIUrl":"10.5653/cerm.2025.08228","url":null,"abstract":"<p><strong>Objective: </strong>In this study, we investigated whether adding autologous platelet-rich plasma (PRP) to the culture medium affects embryo development and clinical outcomes in patients with recurrent implantation failure (RIF).</p><p><strong>Methods: </strong>This study included 201 patients with previous RIF. Of these, 77 opted to receive the treatment and were assigned to the PRP group, and 124 declined and were assigned to the control group. In the PRP group, normally fertilized embryos were cultured in medium supplemented with 5% PRP, whereas embryos in the control group were cultured without PRP. Embryo transfer was performed on day 3 after evaluation of embryo quality. A comparative analysis was then conducted between the two groups, focusing on embryo quality and clinical outcomes.</p><p><strong>Results: </strong>Although no significant differences were observed in fertilization or cleavage rates, the PRP group had a significantly higher proportion of good-quality embryos with at least six cells on day 3 than the control group. The clinical pregnancy and implantation rates in the PRP group were also significantly higher than those in the control group. Furthermore, the ongoing pregnancy rate was notably higher in the PRP group, and successful live births were achieved. Miscarriage rates were similar between groups.</p><p><strong>Conclusion: </strong>Incorporating PRP as an additive into the culture medium improved embryo quality and increased implantation, clinical pregnancy, and ongoing pregnancy rates.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"367-375"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-10DOI: 10.5653/cerm.2024.07612
Nour A M El-Goly, Ahmed M Maged, Nehal Bassiouny, Safaa I Mahmoud, Amira Shoab
To assess the effects of endometrial scratch injury (ESI) in infertile couples seeking fertility through non-in vitro fertilization (IVF) cycles. We conducted a comprehensive search of MEDLINE, EMBASE, Web of Science, Scopus, the Cochrane Library, and Google Scholar from their inception through August 2023. The search terms included 'endometrial scratch,' 'infertility,' 'implantation,' 'intrauterine insemination (IUI),' and their corresponding MeSH terms. We included all published and unpublished randomized controlled trials involving ESI in women undergoing either natural or IUI cycles. The ESIs varied in severity and were performed during either the follicular or luteal phase of the same or preceding cycle. Our review encompassed 32 studies, totaling 5,897 participants. Of these, seven studies with 1,094 participants assessed ESI in natural cycles, while 25 studies with 4,803 participants evaluated it in IUI cycles. The data extracted included trial location, number of participants, inclusion and exclusion criteria for participants, details of the ESI, and outcome parameters (trial registration: CRD42023434127). ESI significantly increased the clinical pregnancy rate (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.72 to 2.47; p<0.001), ongoing pregnancy/live birth rate (OR, 1.68; 95% CI, 1.32 to 2.13; p<0.001), and chemical pregnancy rate (OR, 2.32; 95% CI, 1.79 to 3.00; p<0.001). However, it had no significant effect on the rates of multiple pregnancy, miscarriage, and ectopic pregnancy (p>0.05). ESI improved the clinical pregnancy rate, ongoing pregnancy/live birth rate, and chemical pregnancy rate in both natural and IUI cycles.
评估子宫内膜划伤(ESI)对通过非体外受精(IVF)周期寻求生育的不育夫妇的影响。我们对MEDLINE、EMBASE、Web of Science、Scopus、Cochrane Library和谷歌Scholar从成立到2023年8月进行了全面的检索。搜索词包括“子宫内膜划伤”、“不孕”、“植入”、“宫内人工授精(IUI)”以及相应的MeSH术语。我们纳入了所有已发表和未发表的随机对照试验,这些试验涉及ESI在自然周期或人工授精周期妇女中的应用。妊娠的严重程度不同,在同一周期或前一个周期的卵泡期或黄体期进行。我们的综述包括32项研究,总共5897名参与者。其中,7项研究(1094名参与者)评估了自然周期中的ESI,而25项研究(4803名参与者)评估了IUI周期中的ESI。提取的数据包括试验地点、受试者人数、受试者的纳入和排除标准、ESI详细信息和结局参数(试验注册号:CRD42023434127)。ESI显著提高临床妊娠率(优势比[OR], 2.06; 95%可信区间[CI], 1.72 ~ 2.47; p0.05)。ESI提高了自然周期和人工授精周期的临床妊娠率、持续妊娠/活产率和化学妊娠率。
{"title":"The value of endometrial scratch injury in infertile women trying to conceive through non-in vitro fertilization cycles: A systematic review and meta-analysis.","authors":"Nour A M El-Goly, Ahmed M Maged, Nehal Bassiouny, Safaa I Mahmoud, Amira Shoab","doi":"10.5653/cerm.2024.07612","DOIUrl":"10.5653/cerm.2024.07612","url":null,"abstract":"<p><p>To assess the effects of endometrial scratch injury (ESI) in infertile couples seeking fertility through non-in vitro fertilization (IVF) cycles. We conducted a comprehensive search of MEDLINE, EMBASE, Web of Science, Scopus, the Cochrane Library, and Google Scholar from their inception through August 2023. The search terms included 'endometrial scratch,' 'infertility,' 'implantation,' 'intrauterine insemination (IUI),' and their corresponding MeSH terms. We included all published and unpublished randomized controlled trials involving ESI in women undergoing either natural or IUI cycles. The ESIs varied in severity and were performed during either the follicular or luteal phase of the same or preceding cycle. Our review encompassed 32 studies, totaling 5,897 participants. Of these, seven studies with 1,094 participants assessed ESI in natural cycles, while 25 studies with 4,803 participants evaluated it in IUI cycles. The data extracted included trial location, number of participants, inclusion and exclusion criteria for participants, details of the ESI, and outcome parameters (trial registration: CRD42023434127). ESI significantly increased the clinical pregnancy rate (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.72 to 2.47; p<0.001), ongoing pregnancy/live birth rate (OR, 1.68; 95% CI, 1.32 to 2.13; p<0.001), and chemical pregnancy rate (OR, 2.32; 95% CI, 1.79 to 3.00; p<0.001). However, it had no significant effect on the rates of multiple pregnancy, miscarriage, and ectopic pregnancy (p>0.05). ESI improved the clinical pregnancy rate, ongoing pregnancy/live birth rate, and chemical pregnancy rate in both natural and IUI cycles.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":"52 4","pages":"310-333"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dayong Lee, Myeong Eun Seong, Hye Jin Chang, Young Sik Choi, Hee Jin Lim, Youngjun Choi, Kyungjoo Hwang, Jin Suk Jo, Jung Ryeol Lee
Objective: The Korean government implemented national insurance coverage for infertility treatment in 2017 and established a nationwide infertility treatment data collection system in 2018. This report analyzes infertility treatment cycles performed in 2022 based on this national registry.
Methods: Data were retrospectively collected from 201 certified infertility treatment institutions in Korea. Standardized treatment forms for intrauterine insemination (IUI) and in vitro fertilization (IVF) were submitted to the Health Insurance Review and Assessment Service for all infertility treatment cycles conducted in 2022.
Results: A total of 200,007 infertility treatment cycles were reported in 2022, consisting of 33,137 IUI cycles and 166,870 IVF cycles. Among IVF cycles, 64.6% were initiated for fresh embryo transfers and 35.4% for frozen-thawed embryo transfers. In IVF cycles, the overall clinical pregnancy rate per embryo transfer was 30.2% for fresh and 42.0% for frozen-thawed embryo transfers. The proportion of single embryo transfers has risen steadily since 2019. The most common indication for IVF was diminished ovarian reserve, while IUI was mainly performed for unexplained or male factor infertility.
Conclusion: Nationwide infertility treatment cycle reporting in Korea has enabled detailed monitoring of infertility treatment trends and outcomes. The data show a substantial increase in IVF utilization, a growing preference for frozen-thawed embryo transfer, and broader adoption of single embryo transfer consistent with global practices. Further integration with birth outcome data and longitudinal patient tracking will be essential to evaluate cumulative success rates and overall effectiveness. This national registry provides a foundation for optimizing infertility care and facilitates international benchmarking.
{"title":"Assisted reproductive technology trends in Korea: Annual report for 2022.","authors":"Dayong Lee, Myeong Eun Seong, Hye Jin Chang, Young Sik Choi, Hee Jin Lim, Youngjun Choi, Kyungjoo Hwang, Jin Suk Jo, Jung Ryeol Lee","doi":"10.5653/cerm.2025.08872","DOIUrl":"10.5653/cerm.2025.08872","url":null,"abstract":"<p><strong>Objective: </strong>The Korean government implemented national insurance coverage for infertility treatment in 2017 and established a nationwide infertility treatment data collection system in 2018. This report analyzes infertility treatment cycles performed in 2022 based on this national registry.</p><p><strong>Methods: </strong>Data were retrospectively collected from 201 certified infertility treatment institutions in Korea. Standardized treatment forms for intrauterine insemination (IUI) and in vitro fertilization (IVF) were submitted to the Health Insurance Review and Assessment Service for all infertility treatment cycles conducted in 2022.</p><p><strong>Results: </strong>A total of 200,007 infertility treatment cycles were reported in 2022, consisting of 33,137 IUI cycles and 166,870 IVF cycles. Among IVF cycles, 64.6% were initiated for fresh embryo transfers and 35.4% for frozen-thawed embryo transfers. In IVF cycles, the overall clinical pregnancy rate per embryo transfer was 30.2% for fresh and 42.0% for frozen-thawed embryo transfers. The proportion of single embryo transfers has risen steadily since 2019. The most common indication for IVF was diminished ovarian reserve, while IUI was mainly performed for unexplained or male factor infertility.</p><p><strong>Conclusion: </strong>Nationwide infertility treatment cycle reporting in Korea has enabled detailed monitoring of infertility treatment trends and outcomes. The data show a substantial increase in IVF utilization, a growing preference for frozen-thawed embryo transfer, and broader adoption of single embryo transfer consistent with global practices. Further integration with birth outcome data and longitudinal patient tracking will be essential to evaluate cumulative success rates and overall effectiveness. This national registry provides a foundation for optimizing infertility care and facilitates international benchmarking.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":"52 4","pages":"299-309"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}