To study the association between CYP19A1 genetic variants and the risk of developing polycystic ovary syndrome (PCOS). The study explored the relationship between the candidate gene CYP19A1 and hyperandrogenism, as well as its interplay with obesity, in PCOS patients compared with healthy controls.
Design
A case-control study with genetic association analysis by tetra-primer amplification refractory mutation system polymerase chain reaction and biochemical analysis.
Subjects
204 women (113 PCOS patients and 91 healthy controls) were included in the present study.
Exposure
CYP19A1 variants (rs700519 and rs2236722) in PCOS women.
Main Outcome Measures
Genotypic and allelic frequencies of CYP19A1 variants (rs2236722 and rs700519) and their impact on androgen metabolism and obesity markers.
Results
The genotypic and allelic frequency of rs2236722 showed statistically significant differences between PCOS cases and controls. A significant association was observed under the dominant model, with an odds ratio of 0.34 (95% confidence interval, 0.16–0.66), as well as under the heterozygous model, where the odds ratio was 2.58 (95% confidence interval, 1.34–4.97). However, rs700519 did not reveal any significant association between the groups. A noticeable statistical difference was observed in the levels of total testosterone, dehydroepiandrosterone sulfate , prolactin, luteinizing hormone/follicle-stimulating hormone , Estradiol/total testosterone ratio, body mass index, and waist-to-hip ratio between the case and control groups . However, no variations in clinical variables were observed among genotypes within the PCOS group.
Conclusion
Our study demonstrates that the CYP19A1 rs2236722 polymorphism significantly correlates with PCOS risk, although rs700519 showed no significant association. The findings suggest that altered aromatase activity linked to rs2236722 may contribute to the hyperandrogenic phenotype observed in PCOS patients. These results enhance our understanding of the genetic basis of PCOS and may have implications for personalized treatment approaches.
{"title":"Impact of CYP19A1 genetic variations on polycystic ovary syndrome: findings from a case-control study","authors":"Hiral Chaudhary Ph.D. , Jalpa Patel Ph.D. , Nayan K. Jain Ph.D. , Sonal Panchal M.D. , Purvi Nanavati M.D. , Mala Singh Ph.D. , Naresh Laddha Ph.D. , Rushikesh Joshi Ph.D.","doi":"10.1016/j.xfss.2025.03.005","DOIUrl":"10.1016/j.xfss.2025.03.005","url":null,"abstract":"<div><h3>Objective</h3><div>To study the association between <span><span>CYP19A1</span></span><span> genetic<span> variants and the risk of developing polycystic ovary syndrome (PCOS). The study explored the relationship between the candidate gene </span></span><em>CYP19A1</em><span> and hyperandrogenism, as well as its interplay with obesity, in PCOS patients compared with healthy controls.</span></div></div><div><h3>Design</h3><div><span><span>A case-control study with genetic association analysis by tetra-primer amplification refractory mutation system </span>polymerase chain reaction and </span>biochemical analysis.</div></div><div><h3>Subjects</h3><div>204 women (113 PCOS patients and 91 healthy controls) were included in the present study.</div></div><div><h3>Exposure</h3><div><em>CYP19A1</em> variants (rs700519 and rs2236722) in PCOS women.</div></div><div><h3>Main Outcome Measures</h3><div>Genotypic and allelic frequencies of <em>CYP19A1</em><span> variants (rs2236722 and rs700519) and their impact on androgen metabolism and obesity markers.</span></div></div><div><h3>Results</h3><div><span>The genotypic and allelic frequency of rs2236722 showed statistically significant differences between PCOS cases and controls. A significant association was observed under the dominant model, with an odds ratio of 0.34 (95% confidence interval, 0.16–0.66), as well as under the heterozygous model, where the odds ratio was 2.58 (95% confidence interval, 1.34–4.97). However, rs700519 did not reveal any significant association between the groups. A noticeable statistical difference was observed in the levels of total testosterone, dehydroepiandrosterone sulfate , prolactin, luteinizing hormone/follicle-stimulating hormone , Estradiol/total testosterone ratio, </span>body mass index, and waist-to-hip ratio between the case and control groups . However, no variations in clinical variables were observed among genotypes within the PCOS group.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the <em>CYP19A1</em> rs2236722 polymorphism significantly correlates with PCOS risk, although rs700519 showed no significant association. The findings suggest that altered aromatase activity linked to rs2236722 may contribute to the hyperandrogenic phenotype observed in PCOS patients. These results enhance our understanding of the genetic basis of PCOS and may have implications for personalized treatment approaches.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 364-373"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756247","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.03.001
Keelee J. McCarty Ph.D., Blair McCallie Ph.D., William B. Schoolcraft M.D., Mandy Katz-Jaffe Ph.D.
<div><h3>Objective</h3><div>Implantation success is dependent on timely molecular signaling to establish embryonic apposition, adhesion, and invasion. In an effort to elucidate this critical period in human reproduction, the objective of this study was to use a novel, time-lapse three-dimensional (3D) in vitro co-culture system to characterize the timing of blastocyst development on the initial stages of implantation.</div></div><div><h3>Design</h3><div>Endometrial biopsies<span> were collected from fertile oocyte<span> donors to generate individual 3D wells of separated monolayers of luminal endometrial epithelial and stromal cells<span><span> for co-culture with an individual blastocyst (n = 72; </span>maternal age = 36.3 ± 5.1 years). After 72 hours of co-culture (CytoSMART Lux3 time-lapse imaging system), blastocysts were evaluated for stage of implantation and separated into two groups: No implantation (no adhesion or invasion) and implantation (complete adhesion and invasion).</span></span></span></div></div><div><h3>Subjects</h3><div>N/A.</div></div><div><h3>Exposure</h3><div>N/A.</div></div><div><h3>Main Outcome Measures</h3><div>Immunohistochemistry<span> and targeted quantitative real-time polymerase chain reaction gene expression were performed on individual blastocysts and on exosome-purified small RNAs derived from supernatant.</span></div></div><div><h3>Results</h3><div><span><span>After successful implantation into the endometrial epithelium<span><span>, correctly timed blastocysts experienced greater duration of apposition and adhesion, delayed onset of invasion, and increased number of spontaneous blastocyst collapse compared with slower developing blastocysts. Additionally, targeted </span>gene expression analysis revealed an upward trend of implantation-promoting genes GATA </span></span>binding protein 3, </span>octamer binding transcription factor 4<span><span><span><span>, and cell death regulatory gene<span> caspase </span></span>protein 3 in correctly timed blastocysts compared with slower developing blastocysts. Interestingly, as blastocysts became more attached to the epithelium, a downward trend of </span>developmental genes<span><span> caudal-related homeobox 2 and </span>bone morphogenic protein 15 was observed. A downward trend of hsa-miR-1-3p and an upward trend of hsa-miR-34b-5p was observed in the supernatant of co-cultured blastocysts that achieved successful implantation in co-culture. Top Kyoto Encyclopedia of Genes and Genomes pathways impacted by these </span></span>microRNAs<span><span> were axon guidance, ubiquitin-mediated </span>proteolysis<span><span>, and neurotrophin </span>signaling pathway.</span></span></span></div></div><div><h3>Conclusion</h3><div>Time-lapse 3D in vitro co-culture revealed that the timing of blastocyst development is critical to the initial stages of implantation. The ability of the trophectoderm to expand, orient, and initiate apposition may contribute to the higher likelihood of
{"title":"Utilization of a three-dimensional in vitro co-culture system to characterize embryonic mechanisms associated with implantation","authors":"Keelee J. McCarty Ph.D., Blair McCallie Ph.D., William B. Schoolcraft M.D., Mandy Katz-Jaffe Ph.D.","doi":"10.1016/j.xfss.2025.03.001","DOIUrl":"10.1016/j.xfss.2025.03.001","url":null,"abstract":"<div><h3>Objective</h3><div>Implantation success is dependent on timely molecular signaling to establish embryonic apposition, adhesion, and invasion. In an effort to elucidate this critical period in human reproduction, the objective of this study was to use a novel, time-lapse three-dimensional (3D) in vitro co-culture system to characterize the timing of blastocyst development on the initial stages of implantation.</div></div><div><h3>Design</h3><div>Endometrial biopsies<span> were collected from fertile oocyte<span> donors to generate individual 3D wells of separated monolayers of luminal endometrial epithelial and stromal cells<span><span> for co-culture with an individual blastocyst (n = 72; </span>maternal age = 36.3 ± 5.1 years). After 72 hours of co-culture (CytoSMART Lux3 time-lapse imaging system), blastocysts were evaluated for stage of implantation and separated into two groups: No implantation (no adhesion or invasion) and implantation (complete adhesion and invasion).</span></span></span></div></div><div><h3>Subjects</h3><div>N/A.</div></div><div><h3>Exposure</h3><div>N/A.</div></div><div><h3>Main Outcome Measures</h3><div>Immunohistochemistry<span> and targeted quantitative real-time polymerase chain reaction gene expression were performed on individual blastocysts and on exosome-purified small RNAs derived from supernatant.</span></div></div><div><h3>Results</h3><div><span><span>After successful implantation into the endometrial epithelium<span><span>, correctly timed blastocysts experienced greater duration of apposition and adhesion, delayed onset of invasion, and increased number of spontaneous blastocyst collapse compared with slower developing blastocysts. Additionally, targeted </span>gene expression analysis revealed an upward trend of implantation-promoting genes GATA </span></span>binding protein 3, </span>octamer binding transcription factor 4<span><span><span><span>, and cell death regulatory gene<span> caspase </span></span>protein 3 in correctly timed blastocysts compared with slower developing blastocysts. Interestingly, as blastocysts became more attached to the epithelium, a downward trend of </span>developmental genes<span><span> caudal-related homeobox 2 and </span>bone morphogenic protein 15 was observed. A downward trend of hsa-miR-1-3p and an upward trend of hsa-miR-34b-5p was observed in the supernatant of co-cultured blastocysts that achieved successful implantation in co-culture. Top Kyoto Encyclopedia of Genes and Genomes pathways impacted by these </span></span>microRNAs<span><span> were axon guidance, ubiquitin-mediated </span>proteolysis<span><span>, and neurotrophin </span>signaling pathway.</span></span></span></div></div><div><h3>Conclusion</h3><div>Time-lapse 3D in vitro co-culture revealed that the timing of blastocyst development is critical to the initial stages of implantation. The ability of the trophectoderm to expand, orient, and initiate apposition may contribute to the higher likelihood of","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 312-320"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674549","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.06.001
Cemil Kaya M.D. , Kübra Nur Kaplan İlhan M.Sc. , Bala Gur Dedeoglu Ph.D. , Mehmet Erdem M.D. , Ahmet Erdem M.D.
Objective
To study the association between serum progesterone (P4) levels on the day of embryo transfer (ET) and the deoxyribonucleic acid methylation of window of implantation-related genes in cervical secretions, in both fresh and frozen ET cycles among women undergoing in vitro fertilization (IVF) treatment.
Design
Single-center retrospective cohort study.
Subjects
Women undergoing ET cycles.
Exposure
Cervicovaginal materials have been used as a noninvasive surrogate in investigations of endometrial conditions and progesterone levels on the day of ET.
Main Outcome Measures
Progesterone levels and methylation changes.
Results
A total of 40 eligible women undergoing IVF-ET cycles were evaluated. On the basis of methylation analyses of CXCL14, EMCN, RARRES1, PAEP, THBS2, and GPX3, no statistically significant correlation was found with the median serum P4 levels on the day of ET. When participants were grouped into quartiles on the basis of P4 levels on the day of ET, no statistically significant differences were observed in the methylation levels of CXCL14, SERPING1, EMCN, RARRES1, PAEP, THBS2, and GPX3. The median P4 levels were significantly lower in the thawed ET group (median, 21.4 ng/mL; interquartile range, 13.3–24.0) than in the fresh transfer group (median, 24.0 ng/mL; interquartile range, 18.0–45.0). No significant differences in gene methylation levels were observed between fresh and thawed transfer types, except for THBS2, which showed significantly lower methylation levels in the thawed group than in the fresh group. Although the median P4 levels were lower on day 3 transfers (16.6 ng/mL) than on day 5 transfers (22.4 ng/mL), the difference was not statistically significant. Similarly, no significant differences in methylation levels were detected when comparing day 3 vs. day 5 ET groups.
Conclusion
No association was found between early and mid-luteal phase P4 levels and methylation changes of implantation-related genes in cervical secretions during both fresh and frozen IVF cycles.
{"title":"Relationship between early and mid-lateal phase progesterone levels and the DNA methylation of WOI-related genes in cervical secretions in fresh and frozen IVF cycles","authors":"Cemil Kaya M.D. , Kübra Nur Kaplan İlhan M.Sc. , Bala Gur Dedeoglu Ph.D. , Mehmet Erdem M.D. , Ahmet Erdem M.D.","doi":"10.1016/j.xfss.2025.06.001","DOIUrl":"10.1016/j.xfss.2025.06.001","url":null,"abstract":"<div><h3>Objective</h3><div>To study the association between serum progesterone (P4) levels on the day of embryo transfer (ET) and the deoxyribonucleic acid methylation of window of implantation-related genes in cervical secretions, in both fresh and frozen ET cycles among women undergoing in vitro fertilization (IVF) treatment.</div></div><div><h3>Design</h3><div>Single-center retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Women undergoing ET cycles.</div></div><div><h3>Exposure</h3><div>Cervicovaginal materials have been used as a noninvasive surrogate in investigations of endometrial conditions and progesterone levels on the day of ET.</div></div><div><h3>Main Outcome Measures</h3><div>Progesterone levels and methylation changes.</div></div><div><h3>Results</h3><div>A total of 40 eligible women undergoing IVF-ET cycles were evaluated. On the basis of methylation analyses of <em>CXCL14</em>, <em>EMCN</em>, <em>RARRES1</em>, <em>PAEP</em>, <em>THBS2</em>, and <em>GPX3</em>, no statistically significant correlation was found with the median serum P4 levels on the day of ET. When participants were grouped into quartiles on the basis of P4 levels on the day of ET, no statistically significant differences were observed in the methylation levels of <em>CXCL14</em>, <em>SERPING1</em>, <em>EMCN</em>, <em>RARRES1</em>, <em>PAEP</em>, <em>THBS2</em>, and <em>GPX3</em>. The median P4 levels were significantly lower in the thawed ET group (median, 21.4 ng/mL; interquartile range, 13.3–24.0) than in the fresh transfer group (median, 24.0 ng/mL; interquartile range, 18.0–45.0). No significant differences in gene methylation levels were observed between fresh and thawed transfer types, except for <em>THBS2</em>, which showed significantly lower methylation levels in the thawed group than in the fresh group. Although the median P4 levels were lower on day 3 transfers (16.6 ng/mL) than on day 5 transfers (22.4 ng/mL), the difference was not statistically significant. Similarly, no significant differences in methylation levels were detected when comparing day 3 vs. day 5 ET groups.</div></div><div><h3>Conclusion</h3><div>No association was found between early and mid-luteal phase P4 levels and methylation changes of implantation-related genes in cervical secretions during both fresh and frozen IVF cycles.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 340-352"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512882","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.07.001
{"title":"Reviewer of the Year 2024. F&S Science celebrates excellence in our world-class reviewers","authors":"","doi":"10.1016/j.xfss.2025.07.001","DOIUrl":"10.1016/j.xfss.2025.07.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 264-265"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710109","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.05.001
Nischelle Kalakota M.D. , Alexander Lemenze Ph.D. , Lea George M.D. , Qingshi Zhao Ph.D. , Tracy Wu M.H.A. , Sara S. Morelli M.D., Ph.D. , Andy V. Babwah Ph.D. , Nataki C. Douglas M.D., Ph.D.
Objective
To characterize the expression of adhesion G protein-coupled receptors (ADGR) in the human endometrium and early mouse pregnancy.
Design
An in silico analysis was performed using a retrospective data set comprised endometrial samples across normo-ovulatory menstrual cycles. Gene expression was then validated using quantitative reverse transcription polymerase chain reaction and mRNA sequencing (mRNA-seq) in prospectively collected endometrial biopsies in the periovulatory and midsecretory stages of natural cycles. Gene expression was also investigated under ovarian stimulation (OS) conditions using mRNA-seq. Early pregnancy mouse models were used to investigate whether trends of dynamic ADGR expression are also conserved in the mouse.
Subjects
Twenty-four women aged 21–42 years.
Exposure
Ovulatory menstrual cycle or OS cycle.
Main Outcome Measures
Gene expression in endometrial biopsies and pregnant mouse uterus.
Results
Fifteen women, aged 21–33 years, were recruited in natural cycles during the proliferative phase (cycle days 10–13; n = 4), periovulatory (luteinizing hormone + 12–24 hours; n = 6) period, and midsecretory (luteinizing hormone + 8–9 days; n = 5) phase. Nine women aged 31–42 years old undergoing in vitro fertilization (without fresh embryo transfer) or oocyte cryopreservation using a gonadotropin releasing hormone antagonist protocol were recruited for the OS cohort in either the periovulatory phase (human chorionic gonadotropin + 2; n = 5) or midsecretory phase (human chorionic gonadotropin + 9; n = 4). The in silico analysis revealed dynamic expression for many ADGRs across the menstrual cycle. Differential gene expression was also seen in the prospective analysis within the menstrual cycle phases and between natural cycle and OS conditions. Within early mouse pregnancy, expression was also found to be altered across several Adgr subfamilies.
Conclusion
The differential gene expression observed between the proliferative and secretory phases of the menstrual cycle, along with changes in expression seen in OS and early mouse pregnancy suggest that ADGR expression is hormonally regulated by estradiol and progesterone.
{"title":"Dynamic expression of endometrial adhesion G protein-coupled receptors during the menstrual cycle and early mouse pregnancy: modulation by ovarian stimulation","authors":"Nischelle Kalakota M.D. , Alexander Lemenze Ph.D. , Lea George M.D. , Qingshi Zhao Ph.D. , Tracy Wu M.H.A. , Sara S. Morelli M.D., Ph.D. , Andy V. Babwah Ph.D. , Nataki C. Douglas M.D., Ph.D.","doi":"10.1016/j.xfss.2025.05.001","DOIUrl":"10.1016/j.xfss.2025.05.001","url":null,"abstract":"<div><h3>Objective</h3><div>To characterize the expression of adhesion G protein-coupled receptors (ADGR) in the human endometrium<span> and early mouse pregnancy.</span></div></div><div><h3>Design</h3><div><span><span>An in silico analysis was performed using a retrospective data set comprised endometrial samples across normo-ovulatory </span>menstrual cycles<span>. Gene expression was then validated using quantitative reverse transcription polymerase chain reaction and mRNA sequencing (mRNA-seq) in prospectively collected </span></span>endometrial biopsies<span> in the periovulatory and midsecretory stages of natural cycles. Gene expression was also investigated under ovarian stimulation (OS) conditions using mRNA-seq. Early pregnancy<span> mouse models were used to investigate whether trends of dynamic ADGR expression are also conserved in the mouse.</span></span></div></div><div><h3>Subjects</h3><div>Twenty-four women aged 21–42 years.</div></div><div><h3>Exposure</h3><div>Ovulatory menstrual cycle or OS cycle.</div></div><div><h3>Main Outcome Measures</h3><div>Gene expression in endometrial biopsies and pregnant mouse uterus.</div></div><div><h3>Results</h3><div><span><span>Fifteen women, aged 21–33 years, were recruited in natural cycles during the proliferative phase (cycle days 10–13; n = 4), periovulatory (luteinizing hormone + 12–24 hours; n = 6) period, and midsecretory (luteinizing hormone + 8–9 days; n = 5) phase. Nine women aged 31–42 years old undergoing in vitro fertilization (without fresh embryo transfer) or </span>oocyte<span><span> cryopreservation using a </span>gonadotropin releasing hormone antagonist protocol were recruited for the OS cohort in either the periovulatory phase (human chorionic gonadotropin + 2; n = 5) or midsecretory phase (human chorionic gonadotropin + 9; n = 4). The in silico analysis revealed dynamic expression for many </span></span><em>ADGRs</em><span> across the menstrual cycle. Differential gene expression was also seen in the prospective analysis within the menstrual cycle phases and between natural cycle and OS conditions. Within early mouse pregnancy, expression was also found to be altered across several </span><em>Adgr</em> subfamilies.</div></div><div><h3>Conclusion</h3><div>The differential gene expression observed between the proliferative and secretory phases of the menstrual cycle, along with changes in expression seen in OS and early mouse pregnancy suggest that <em>ADGR</em><span><span> expression is hormonally regulated by estradiol and </span>progesterone.</span></div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 321-339"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095920","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}
To determine whether drug-free in vitro activation (IVA) with immediate autotransplantation improves reproductive outcomes and ovarian blood flow in patients with poor ovarian response (POR) and premature ovarian insufficiency (POI).
Design
A clinical trial.
Setting
A tertiary university-affiliated hospital.
Patient(s)
Twenty-one women diagnosed with POR (n = 7) and POI (n = 14).
Intervention(s)
Drug-free IVA through mechanical ovarian tissue disruption and immediate autotransplantation.
Main Outcome Measure(s)
Changes in antral follicle count, antimüllerian hormone levels, ovarian volume, Doppler indices, oocyte retrieval rates, and embryo cryopreservation.
Result(s)
After drug-free IVA, the antral follicle count increased in 71% of patients with POR and 50% of patients with POI, whereas the antimüllerian hormone levels improved in 57% of patients with POR and 7% of patients with POI. A significant increase in ovarian volume was noted in patients with POR and in patients with POI who exhibited follicle growth after IVA. Doppler indices revealed no significant changes in ovarian blood flow. Follicle development was achieved in all patients with POR and 10 of 14 patients with POI, facilitating successful oocyte retrieval in all patients with POR and 7 of 14 patients with POI. The fertilization rates were 72% and 59% for patients with POR and POI, respectively. All patients with POR and 5 of 14 patients with POI had at least 1 embryo cryopreserved. Among the 11 patients who underwent frozen embryo transfer, 2 clinical pregnancies were achieved, resulting in 1 live birth.
Conclusion(s)
Drug-free IVA demonstrates potential in improving follicular activity, oocyte retrieval, and embryo cryopreservation. However, clinical application remains challenging due to modest success rates, necessitating further protocol refinements and long-term outcome evaluations.
{"title":"Drug-free in vitro activation of ovarian follicles and fresh tissue autotransplantation in patients with poor ovarian response and premature ovarian insufficiency","authors":"Leonti Grin M.D. , Roza Berkovitz-Shperling M.D. , Gal Goldstein M.D. , Yulia Michailov Ph.D. , Ofer Gemer M.D. , Eyal Anteby M.D. , Kazuhiro Kawamura M.D. , Bozhena Saar-Ryss M.D. , Shevach Friedler M.D.","doi":"10.1016/j.xfss.2025.04.002","DOIUrl":"10.1016/j.xfss.2025.04.002","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether drug-free in vitro activation (IVA) with immediate autotransplantation<span> improves reproductive outcomes and ovarian blood flow in patients with poor ovarian response (POR) and premature ovarian insufficiency (POI).</span></div></div><div><h3>Design</h3><div>A clinical trial.</div></div><div><h3>Setting</h3><div>A tertiary university-affiliated hospital.</div></div><div><h3>Patient(s)</h3><div>Twenty-one women diagnosed with POR (n = 7) and POI (n = 14).</div></div><div><h3>Intervention(s)</h3><div>Drug-free IVA through mechanical ovarian tissue disruption and immediate autotransplantation.</div></div><div><h3>Main Outcome Measure(s)</h3><div>Changes in antral follicle<span><span> count, antimüllerian hormone levels, ovarian volume, Doppler indices, </span>oocyte retrieval<span> rates, and embryo cryopreservation.</span></span></div></div><div><h3>Result(s)</h3><div>After drug-free IVA, the antral follicle count increased in 71% of patients with POR and 50% of patients with POI, whereas the antimüllerian hormone levels improved in 57% of patients with POR and 7% of patients with POI. A significant increase in ovarian volume was noted in patients with POR and in patients with POI who exhibited follicle growth after IVA. Doppler indices revealed no significant changes in ovarian blood flow. Follicle development<span> was achieved in all patients with POR and 10 of 14 patients with POI, facilitating successful oocyte retrieval in all patients with POR and 7 of 14 patients with POI. The fertilization<span> rates were 72% and 59% for patients with POR and POI, respectively. All patients with POR and 5 of 14 patients with POI had at least 1 embryo cryopreserved. Among the 11 patients who underwent frozen embryo transfer, 2 clinical pregnancies were achieved, resulting in 1 live birth.</span></span></div></div><div><h3>Conclusion(s)</h3><div>Drug-free IVA demonstrates potential in improving follicular activity, oocyte retrieval, and embryo cryopreservation. However, clinical application remains challenging due to modest success rates, necessitating further protocol refinements and long-term outcome evaluations.</div></div><div><h3>Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (Identifier: NCT04024722).</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 303-311"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043003","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.03.007
Adnan Fadhel Al-Azaawie M.Sc. , Ahmed AbdulJabbar Suleiman Ph.D. , Mousa Jasim Mohammed Ph.D.
Objective
To investigate the correlation between piwi-interacting RNA (piRNA) expression and steroid 5 alpha reductase type 2 (SRD5A2) mRNA regulation in seminal fluid across various male infertility conditions (asthenozoospermia, oligozoospermia, and azoospermia).
Design and Subjects
This study included 88 male participants aged 20–40 years, categorized into infertility and normozoospermic groups.
Exposure
Seminal fluid analysis and RNA extraction were performed to quantify SRD5A2 mRNA and selected piRNAs (hsa-piR-002528, hsa-piR-017183, hsa-piR-023244, and hsa-piR-023338) using qRT-PCR.
Main Outcome Measures
Correlation analysis evaluated interactions between piRNA levels and SRD5A2 expression. Statistical significance was determined using analysis of variance and correlation coefficients.
Results
Seminal Fluid Analysis: significant differences in seminal volume, sperm morphology, count, and motility were observed across infertility subtypes. Steroid 5 alpha reductase type 2 Expression: asthenozoospermia showed up-regulated SRD5A2 mRNA (Log2FC = 0.333), whereas oligozoospermia and azoospermia exhibited down-regulation (Log2FC = −0.470 and −0.688, respectively). Piwi-interacting RNA Expression: hsa-piR-002528 and hsa-piR-017183 were up-regulated in all infertility subtypes, whereas hsa-piR-023244 and hsa-piR-023338 exhibited subtype-specific expression patterns. Correlation Analysis: Steroid 5 alpha reductase type 2 mRNA negatively correlated with hsa-piR-002528 and hsa-piR-023338, suggesting regulatory interactions affecting sperm motility and count. Positive correlations were observed for hsa-piR-023244 in azoospermia, indicating potential roles in supporting spermatogenesis.
Conclusions
Altered piRNA profiles and SRD5A2 expression are associated with male infertility subtypes. These findings highlight the regulatory role of piRNAs in spermatogenesis and their potential as biomarkers and therapeutic targets for male infertility.
{"title":"Unveiling the molecular cross-talk between piwi-interacting RNAs and steroid 5 alpha reductase type 2 in sperm dysfunction","authors":"Adnan Fadhel Al-Azaawie M.Sc. , Ahmed AbdulJabbar Suleiman Ph.D. , Mousa Jasim Mohammed Ph.D.","doi":"10.1016/j.xfss.2025.03.007","DOIUrl":"10.1016/j.xfss.2025.03.007","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the correlation between piwi-interacting RNA (piRNA) expression and steroid 5 alpha reductase type 2<span><span> (SRD5A2) mRNA regulation in seminal fluid across various male infertility conditions (asthenozoospermia, </span>oligozoospermia, and azoospermia).</span></div></div><div><h3>Design and Subjects</h3><div>This study included 88 male participants aged 20–40 years, categorized into infertility and normozoospermic groups.</div></div><div><h3>Exposure</h3><div>Seminal fluid analysis and RNA extraction were performed to quantify SRD5A2 mRNA and selected piRNAs (hsa-piR-002528, hsa-piR-017183, hsa-piR-023244, and hsa-piR-023338) using qRT-PCR.</div></div><div><h3>Main Outcome Measures</h3><div>Correlation analysis evaluated interactions between piRNA levels and SRD5A2 expression. Statistical significance was determined using analysis of variance and correlation coefficients.</div></div><div><h3>Results</h3><div><span><span>Seminal Fluid Analysis: significant differences in seminal volume, sperm morphology, count, and motility were observed across infertility subtypes. Steroid 5 alpha reductase<span> type 2 Expression: asthenozoospermia<span> showed up-regulated SRD5A2 mRNA (Log2FC = 0.333), whereas oligozoospermia and azoospermia exhibited down-regulation (Log2FC = −0.470 and −0.688, respectively). Piwi-interacting RNA Expression: hsa-piR-002528 and hsa-piR-017183 were up-regulated in all infertility subtypes, whereas hsa-piR-023244 and hsa-piR-023338 exhibited subtype-specific expression patterns. Correlation Analysis: Steroid 5 alpha reductase type 2 mRNA negatively correlated with hsa-piR-002528 and hsa-piR-023338, suggesting regulatory interactions affecting </span></span></span>sperm motility and count. Positive correlations were observed for hsa-piR-023244 in azoospermia, indicating potential roles in supporting </span>spermatogenesis.</div></div><div><h3>Conclusions</h3><div>Altered piRNA profiles and SRD5A2 expression are associated with male infertility subtypes. These findings highlight the regulatory role of piRNAs in spermatogenesis and their potential as biomarkers and therapeutic targets for male infertility.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 282-292"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008843","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}
To study the effects of generally considered safe doses of antioxidant micronutrient supplementation on semen parameters, systemic redox balance, sperm DNA structural integrity, and fertility.
Design
Given ethical limitations in human studies, this dose escalation study examined the effects of common water-soluble antioxidant micronutrients (vitamin C, zinc, folate, and carnitine) on semen parameters, redox status, DNA integrity, and fertility outcomes in healthy male mice over one spermatogenic cycle. The study was partially repeated at the highest carnitine dose for pregnancy outcomes and comparatively assessed in subfertile, oxidatively stressed mice.
Subjects
“Fertile/healthy” (CD1) and “Subfertile/oxidatively stressed” (gpx5-/-) mice.
Exposure
Water-soluble micronutrients (vitamin C, zinc, folate, and carnitine).
Main Outcome Measures
Sperm parameters included count, motility, viability, and acrosome integrity. Systemic redox status was evaluated in blood, measuring malondialdehyde, thiol levels, and total antioxidant capacity. Sperm DNA parameters were examined for oxidation (8-OHdG staining), fragmentation (TUNEL), and decondensation (toluidine blue). Pregnancy outcomes were also assessed in CD1 mice fed carnitine.
Results
In healthy mice, increasing doses of individual micronutrients had minimal effects on semen parameters. However, high doses of all four micronutrients significantly disrupted the redox balance in blood plasma and compromised sperm DNA integrity in an ingredient-specific manner. Moderate to high doses of carnitine caused severe DNA fragmentation, a finding confirmed in a subsequent experiment using the highest carnitine dose. In this follow-up experiment, male mice supplemented with carnitine and mated with females showed decreased pregnancy rates and fewer total pups born. Conversely, in oxidatively stressed mice, high-dose carnitine had the opposite, beneficial effect of improving sperm DNA integrity.
Conclusions
At high doses, antioxidants can induce reductive stress, damaging vital molecular components of sperm cells such as DNA. Although strong evidence supports the use of preconception antioxidants to boost semen quality, healthcare professionals should assess oxidative stress levels when possible and recommend personalized antioxidant doses to avoid reductive stress and prevent adverse reproductive outcomes.
{"title":"The dual nature of micronutrients on fertility: too much of a good thing?","authors":"Aron Moazamian Ph.D. , Elisa Hug Ph.D. , Pauline Villeneuve M.Sc. , Stéphanie Bravard B.Sc. , Richard Geurtsen Ph.D. , Jorge Hallak M.D., Ph.D. , Fabrice Saez Ph.D. , Robert John Aitken Ph.D., Sc.D. , Parviz Gharagozloo Ph.D. , Joël R. Drevet Ph.D.","doi":"10.1016/j.xfss.2025.02.004","DOIUrl":"10.1016/j.xfss.2025.02.004","url":null,"abstract":"<div><h3>Objective</h3><div>To study the effects of generally considered safe doses of antioxidant micronutrient supplementation on semen parameters, systemic redox balance, sperm DNA structural integrity, and fertility.</div></div><div><h3>Design</h3><div>Given ethical limitations in human studies, this dose escalation study examined the effects of common water-soluble antioxidant micronutrients (vitamin C, zinc, folate, and carnitine) on semen parameters, redox status, DNA integrity, and fertility outcomes in healthy male mice over one spermatogenic cycle. The study was partially repeated at the highest carnitine dose for pregnancy outcomes and comparatively assessed in subfertile, oxidatively stressed mice.</div></div><div><h3>Subjects</h3><div>“Fertile/healthy” (CD1) and “Subfertile/oxidatively stressed” (<em>gpx5</em><sup>-/-</sup>) mice.</div></div><div><h3>Exposure</h3><div>Water-soluble micronutrients (vitamin C, zinc, folate, and carnitine).</div></div><div><h3>Main Outcome Measures</h3><div>Sperm parameters included count, motility, viability, and acrosome integrity. Systemic redox status was evaluated in blood, measuring malondialdehyde, thiol levels, and total antioxidant capacity. Sperm DNA parameters were examined for oxidation (8-OHdG staining), fragmentation (TUNEL), and decondensation (toluidine blue). Pregnancy outcomes were also assessed in CD1 mice fed carnitine.</div></div><div><h3>Results</h3><div>In healthy mice, increasing doses of individual micronutrients had minimal effects on semen parameters. However, high doses of all four micronutrients significantly disrupted the redox balance in blood plasma and compromised sperm DNA integrity in an ingredient-specific manner. Moderate to high doses of carnitine caused severe DNA fragmentation, a finding confirmed in a subsequent experiment using the highest carnitine dose. In this follow-up experiment, male mice supplemented with carnitine and mated with females showed decreased pregnancy rates and fewer total pups born. Conversely, in oxidatively stressed mice, high-dose carnitine had the opposite, beneficial effect of improving sperm DNA integrity.</div></div><div><h3>Conclusions</h3><div>At high doses, antioxidants can induce reductive stress, damaging vital molecular components of sperm cells such as DNA. Although strong evidence supports the use of preconception antioxidants to boost semen quality, healthcare professionals should assess oxidative stress levels when possible and recommend personalized antioxidant doses to avoid reductive stress and prevent adverse reproductive outcomes.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 293-302"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525349","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 : 2025-08-01DOI: 10.1016/j.xfss.2025.03.004
Magdalena Peeva M.D. , Ahmad Badeghiesh M.D., M.P.H. , Haitham Baghlaf M.D., M.P.H. , Michael H. Dahan M.D.
Objective
To determine the independent effect of ethnicity on obstetric outcomes in women with polycystic ovary syndrome (PCOS).
Design
This was a retrospective, population-based cohort study using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2004 to 2014. Women with PCOS were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Pregnancy, delivery, and neonatal outcomes were compared across ethnic groups. The chi-square tests assessed baseline characteristics, and logistic regression was used to evaluate associations between ethnicity and outcomes, estimating odds ratios (ORs) and 95% confidence intervals (CIs).
Subjects
A total of 12,782 pregnant women with PCOS were identified between 2004 and 2014, categorized by ethnicity: White (n = 9,107); African American (n = 1,098); Hispanic (n = 1,288); and Asian (n = 741).
Exposure
The exposure of interest was maternal ethnicity and its association with pregnancy, delivery, and neonatal outcomes among women with PCOS.
Main Outcome Measures
Pregnancy, delivery, and neonatal complications were assessed across ethnic groups.
Results
Asian women had a higher odds of having gestational diabetes (adjusted OR [aOR], 1.96; 95% CI, 1.49–2.58), chorioamnionitis (aOR, 3.41; 95% CI, 2.12–5.47), operative vaginal delivery (aOR, 2.42; 95% CI, 1.65–3.56), postpartum hemorrhage (PPH) (aOR, 2.07; 95% CI, 1.25–3.43), and maternal infection (aOR, 2.84; 95% CI, 1.80–4.49). African Americans had a higher risk of pregnancy-induced hypertension (aOR, 1.38; 95% CI, 1.06–1.80), preeclampsia (aOR, 1.68; 95% CI, 1.15–2.45), preterm premature rupture of membrane (aOR, 2.75; 95% CI, 1.58–4.78), chorioamnionitis (aOR, 1.83; 95% CI, 1.12–2.98), and cesarean sections (aOR, 1.69; 95% CI, 1.32–2.15) and lower risk of operative vaginal delivery (aOR, 0.53; 95% CI, 0.31–0.93), spontaneous vaginal delivery (aOR, 0.67; 95% CI, 0.52–0.85), and maternal infection (aOR, 1.91; 95% CI, 1.21–3.00). The risk of gestational diabetes (aOR, 1.36; 95% CI, 1.06–1.73) and PPH (aOR, 1.58; 95% CI, 1.01–2.47) increased among Hispanic patients. Caucasian patients were at lower risk of gestational diabetes (aOR, 0.67; 95% CI, 0.57–0.79), chorioamnionitis (aOR, 0.39; 95% CI, 0.28–0.55), cesarean section (aOR, 0.83; 95% CI, 0.73–0.95), PPH (aOR, 0.70; 95% CI, 0.50–0.98), blood transfusion (aOR, 0.49; 95% CI, 0.29–0.83), maternal infection (aOR, 0.34; 95% CI, 0.27–0.51), and small-for-gestational-age infants (aOR, 0.64; 95% CI, 0.44–0.93) and had higher odds of having a spontaneous vaginal delivery (aOR, 1.25; 95% CI, 1.10–1.43).
{"title":"The role of ethnicity and polycystic ovary syndrome on pregnancy complications: an analysis of a population database","authors":"Magdalena Peeva M.D. , Ahmad Badeghiesh M.D., M.P.H. , Haitham Baghlaf M.D., M.P.H. , Michael H. Dahan M.D.","doi":"10.1016/j.xfss.2025.03.004","DOIUrl":"10.1016/j.xfss.2025.03.004","url":null,"abstract":"<div><h3>Objective</h3><div><span>To determine the independent effect of ethnicity on obstetric outcomes in women with </span>polycystic ovary syndrome (PCOS).</div></div><div><h3>Design</h3><div><span>This was a retrospective, population-based cohort study using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2004 to 2014. Women with PCOS were identified using the </span>International Classification of Diseases<span>, Ninth Revision, Clinical Modification codes. Pregnancy, delivery, and neonatal outcomes were compared across ethnic groups. The chi-square tests assessed baseline characteristics, and logistic regression was used to evaluate associations between ethnicity and outcomes, estimating odds ratios (ORs) and 95% confidence intervals (CIs).</span></div></div><div><h3>Subjects</h3><div>A total of 12,782 pregnant women with PCOS were identified between 2004 and 2014, categorized by ethnicity: White (n = 9,107); African American (n = 1,098); Hispanic (n = 1,288); and Asian (n = 741).</div></div><div><h3>Exposure</h3><div>The exposure of interest was maternal ethnicity and its association with pregnancy, delivery, and neonatal outcomes among women with PCOS.</div></div><div><h3>Main Outcome Measures</h3><div>Pregnancy, delivery, and neonatal complications were assessed across ethnic groups.</div></div><div><h3>Results</h3><div><span><span>Asian women had a higher odds of having gestational diabetes (adjusted OR [aOR], 1.96; 95% CI, 1.49–2.58), </span>chorioamnionitis<span> (aOR, 3.41; 95% CI, 2.12–5.47), operative vaginal delivery<span> (aOR, 2.42; 95% CI, 1.65–3.56), postpartum hemorrhage<span> (PPH) (aOR, 2.07; 95% CI, 1.25–3.43), and maternal infection (aOR, 2.84; 95% CI, 1.80–4.49). African Americans had a higher risk of pregnancy-induced hypertension (aOR, 1.38; 95% CI, 1.06–1.80), preeclampsia (aOR, 1.68; 95% CI, 1.15–2.45), preterm </span></span></span></span>premature rupture of membrane<span><span> (aOR, 2.75; 95% CI, 1.58–4.78), chorioamnionitis (aOR, 1.83; 95% CI, 1.12–2.98), and cesarean sections (aOR, 1.69; 95% CI, 1.32–2.15) and lower risk of operative vaginal delivery (aOR, 0.53; 95% CI, 0.31–0.93), spontaneous vaginal delivery (aOR, 0.67; 95% CI, 0.52–0.85), and maternal infection (aOR, 1.91; 95% CI, 1.21–3.00). The risk of gestational diabetes (aOR, 1.36; 95% CI, 1.06–1.73) and PPH (aOR, 1.58; 95% CI, 1.01–2.47) increased among Hispanic patients. Caucasian patients were at lower risk of gestational diabetes (aOR, 0.67; 95% CI, 0.57–0.79), chorioamnionitis (aOR, 0.39; 95% CI, 0.28–0.55), cesarean section (aOR, 0.83; 95% CI, 0.73–0.95), PPH (aOR, 0.70; 95% CI, 0.50–0.98), </span>blood transfusion (aOR, 0.49; 95% CI, 0.29–0.83), maternal infection (aOR, 0.34; 95% CI, 0.27–0.51), and small-for-gestational-age infants (aOR, 0.64; 95% CI, 0.44–0.93) and had higher odds of having a spontaneous vaginal delivery (aOR, 1.25; 95% CI, 1.10–1.43).</span></div></div><div><h3>Conclusion</h3><div>Among w","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 3","pages":"Pages 353-363"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744424","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}
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