Pub Date : 2023-11-01DOI: 10.1016/j.xfss.2023.09.003
Jesús Cadenas Ph.D. , Susanne Elisabeth Pors Ph.D. , Caroline Pulz Hansen M.Sc. , Sarah Maria Olufsen M.Sc. , Cristina Subiran M.Sc. , Jane Alrø Bøtkjær Ph.D. , Liv La Cour Poulsen M.D., Ph.D. , Jens Fedder M.D., Ph.D. , Margit Dueholm M.D., Ph.D. , Lotte Berdiin Colmorn M.D., Ph.D. , Stine Gry Kristensen Ph.D. , Linn Salto Mamsen Ph.D. , Claus Yding Andersen D.M.Sc.
Objective
To characterize the growth factor midkine (MDK) in the human ovary to determine whether MDK is produced locally within the ovary, examine whether different ovarian cell types are more likely to produce MDK, and determine whether there are any stage-specific variations during follicle growth. Previous studies have revealed that MDK potentially affects human follicle growth and oocyte maturation. Proteomic analyses in follicular fluid (FF) have identified MDK to functionally cluster together and follow a similar expression profile to that of well-known proteins involved in ovarian follicle development. Midkine has not yet been characterized in the human ovary.
Design
Descriptive study.
Setting
University Hospital.
Patients
The study included samples from 121 patients: 71 patients (aged 17–37 years) who underwent ovarian tissue cryopreservation provided granulosa cells (GC), cumulus cells, ovarian cortex, medulla tissue, and FF from small antral follicles (SAF); and 50 patients (aged 20–35 years) receiving in vitro fertilization treatment provided FF from preovulatory follicles before and after induction of final follicle maturation.
Interventions
None.
Main Outcome Measures
MDK relative gene expression was quantified using a real-time quantitative polymerase chain reaction in cumulus cells, GC, and medulla tissue. Additionally, immunostaining and western blotting assays were used to detect MDK protein in the ovarian cortex, which contains preantral follicles, SAF, and medulla tissue. Furthermore, enzyme-linked immunosorbent assay analyses were performed to measure the concentration of MDK in FF aspirated from SAF and preovulatory follicles both before and 36 hours after inducing the final maturation of follicles.
Results
Immunostaining and reverse transcription-quantitative polymerase chain reaction revealed a more prominent expression of MDK in GC compared with other ovarian cell types. Intrafollicular MDK concentration was significantly higher in SAF compared with preovulatory follicles. In addition, different molecular weight species of MDK were detected using western blotting in various ovarian sample types: GC and FF samples presented primarily one band of approximately 15 kDa and an additional band of approximately 13 kDa, although other bands with higher molecular weight (between 30 and 38 kDa) were detected in medulla tissue.
Conclusions
This is the first time that MDK has been immunolocalized in human ovarian cells at the protein level and that potentially different MDK variants have been detected in human FF, GC, and ovarian medulla tissue. Future studies are needed to sequence and identify the different potential MDK variants
{"title":"Midkine characterization in human ovaries: potential new variants in follicles","authors":"Jesús Cadenas Ph.D. , Susanne Elisabeth Pors Ph.D. , Caroline Pulz Hansen M.Sc. , Sarah Maria Olufsen M.Sc. , Cristina Subiran M.Sc. , Jane Alrø Bøtkjær Ph.D. , Liv La Cour Poulsen M.D., Ph.D. , Jens Fedder M.D., Ph.D. , Margit Dueholm M.D., Ph.D. , Lotte Berdiin Colmorn M.D., Ph.D. , Stine Gry Kristensen Ph.D. , Linn Salto Mamsen Ph.D. , Claus Yding Andersen D.M.Sc.","doi":"10.1016/j.xfss.2023.09.003","DOIUrl":"10.1016/j.xfss.2023.09.003","url":null,"abstract":"<div><h3>Objective</h3><p><span><span>To characterize the growth factor midkine (MDK) in the human ovary to determine whether MDK is produced locally within the ovary, examine whether different ovarian cell types are more likely to produce MDK, and determine whether there are any stage-specific variations during follicle growth. Previous studies have revealed that MDK potentially affects human follicle growth and </span>oocyte maturation<span>. Proteomic analyses in follicular fluid (FF) have identified MDK to functionally cluster together and follow a similar expression profile to that of well-known proteins involved in ovarian </span></span>follicle development. Midkine has not yet been characterized in the human ovary.</p></div><div><h3>Design</h3><p>Descriptive study.</p></div><div><h3>Setting</h3><p>University Hospital.</p></div><div><h3>Patients</h3><p>The study included samples from 121 patients: 71 patients (aged 17–37 years) who underwent ovarian tissue cryopreservation<span><span><span><span> provided granulosa cells (GC), </span>cumulus cells, ovarian cortex, medulla tissue, and FF from small </span>antral follicles (SAF); and 50 patients (aged 20–35 years) receiving in vitro fertilization </span>treatment<span> provided FF from preovulatory follicles before and after induction of final follicle maturation.</span></span></p></div><div><h3>Interventions</h3><p>None.</p></div><div><h3>Main Outcome Measures</h3><p>MDK relative gene expression was quantified using a real-time quantitative polymerase chain reaction in cumulus cells, GC, and medulla tissue. Additionally, immunostaining<span> and western blotting assays were used to detect MDK protein in the ovarian cortex, which contains preantral follicles, SAF, and medulla tissue. Furthermore, enzyme-linked immunosorbent assay analyses were performed to measure the concentration of MDK in FF aspirated from SAF and preovulatory follicles both before and 36 hours after inducing the final maturation of follicles.</span></p></div><div><h3>Results</h3><p>Immunostaining and reverse transcription-quantitative polymerase chain reaction revealed a more prominent expression of MDK in GC compared with other ovarian cell types. Intrafollicular MDK concentration was significantly higher in SAF compared with preovulatory follicles. In addition, different molecular weight species of MDK were detected using western blotting in various ovarian sample types: GC and FF samples presented primarily one band of approximately 15 kDa and an additional band of approximately 13 kDa, although other bands with higher molecular weight (between 30 and 38 kDa) were detected in medulla tissue.</p></div><div><h3>Conclusions</h3><p>This is the first time that MDK has been immunolocalized in human ovarian cells at the protein level and that potentially different MDK variants have been detected in human FF, GC, and ovarian medulla tissue. Future studies are needed to sequence and identify the different potential MDK variants","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180627","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.06.003
Ayman Al-Hendy M.D., Ph.D. , Ying F. Zhou M.D. , Thomas Faustmann M.D. , Esther Groettrup-Wolfers M.D. , Kaisa Laapas M.Sc. , Susanne Parke M.D. , Christian Seitz M.D.
Objective
Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.
Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.
Intervention(s)
Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.
Main Outcome Measure(s)
Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.
Result(s)
Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.
Conclusion(s)
Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.
{"title":"Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial","authors":"Ayman Al-Hendy M.D., Ph.D. , Ying F. Zhou M.D. , Thomas Faustmann M.D. , Esther Groettrup-Wolfers M.D. , Kaisa Laapas M.Sc. , Susanne Parke M.D. , Christian Seitz M.D.","doi":"10.1016/j.xfss.2023.06.003","DOIUrl":"10.1016/j.xfss.2023.06.003","url":null,"abstract":"<div><h3>Objective</h3><p>Vilaprisan is a highly potent selective progesterone receptor modulator<span><span> shown to reduce heavy menstrual bleeding, induce </span>amenorrhea<span>, and diminish uterine fibroid<span> volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.</span></span></span></p></div><div><h3>Design</h3><p>Randomized, double-blind, placebo-controlled, multicenter phase 3 study.</p></div><div><h3>Setting</h3><p>Hospitals and medical centers.</p></div><div><h3>Patient(s)</h3><p>Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.</p></div><div><h3>Intervention(s)</h3><p>Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.</p></div><div><h3>Result(s)</h3><p>Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, <em>P</em><.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, <em>P</em><.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.</p></div><div><h3>Conclusion(s)</h3><p>Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.</p></div><div><h3>Clinical Trial Registration Number</h3><p>NCT03400943 (<span>ClinicalTrials.gov</span><svg><path></path></svg>).</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940805","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.09.001
Ryan H. Miller M.S. , Elizabeth A. DeVilbiss Ph.D. , Kristin R. Brogaard Ph.D. , Carter R. Norton , Chad A. Pollard B.S. , Benjamin R. Emery M.S. , Kenneth I. Aston Ph.D. , James M. Hotaling M.D., M.S. , Tim G. Jenkins Ph.D.
Objective
To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential.
Design
Retrospective cohort.
Setting
Fertility care centers.
Patients
Male patients seeking infertility treatment and fertile male sperm donors.
Intervention
None.
Main Outcome Measures
Sperm DNA methylation data from 43 fertile sperm donors were analyzed and compared with the data from 1344 men seeking fertility assessment or treatment. Methylation at gene promoters with the least variable methylation in fertile patients was used to create 3 categories of promoter dysregulation in the infertility treatment cohort: poor, average, and excellent sperm quality.
Results
After controlling for female factors, there were significant differences in intrauterine insemination pregnancy and live birth outcomes between the poor and excellent groups across a cumulative average of 2–3 cycles: 19.4% vs. 51.7% (P=.008) and 19.4% vs. 44.8% (P=.03), respectively. Live birth outcomes from in vitro fertilization, primarily with intracytoplasmic sperm injection, were not found to be significantly different among any of the 3 groups.
Conclusion
Methylation variability in a panel of 1233 gene promoters could augment the predictive ability of semen analysis and be a reliable biomarker for assessing intrauterine insemination outcomes. In vitro fertilization with intracytoplasmic sperm injection appears to overcome high levels of epigenetic instability in sperm.
{"title":"Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis","authors":"Ryan H. Miller M.S. , Elizabeth A. DeVilbiss Ph.D. , Kristin R. Brogaard Ph.D. , Carter R. Norton , Chad A. Pollard B.S. , Benjamin R. Emery M.S. , Kenneth I. Aston Ph.D. , James M. Hotaling M.D., M.S. , Tim G. Jenkins Ph.D.","doi":"10.1016/j.xfss.2023.09.001","DOIUrl":"10.1016/j.xfss.2023.09.001","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential.</p></div><div><h3>Design</h3><p>Retrospective cohort.</p></div><div><h3>Setting</h3><p>Fertility care centers.</p></div><div><h3>Patients</h3><p>Male patients seeking infertility treatment and fertile male sperm donors.</p></div><div><h3>Intervention</h3><p>None.</p></div><div><h3>Main Outcome Measures</h3><p>Sperm DNA methylation data from 43 fertile sperm donors were analyzed and compared with the data from 1344 men seeking fertility assessment or treatment. Methylation at gene promoters with the least variable methylation in fertile patients was used to create 3 categories of promoter dysregulation in the infertility treatment cohort: poor, average, and excellent sperm quality.</p></div><div><h3>Results</h3><p>After controlling for female factors, there were significant differences in intrauterine insemination pregnancy and live birth outcomes between the poor and excellent groups across a cumulative average of 2–3 cycles: 19.4% vs. 51.7% (<em>P</em>=.008) and 19.4% vs. 44.8% (<em>P</em>=.03), respectively. Live birth outcomes from in vitro fertilization, primarily with intracytoplasmic sperm injection, were not found to be significantly different among any of the 3 groups.</p></div><div><h3>Conclusion</h3><p>Methylation variability in a panel of 1233 gene promoters could augment the predictive ability of semen analysis and be a reliable biomarker for assessing intrauterine insemination outcomes. In vitro fertilization with intracytoplasmic sperm injection appears to overcome high levels of epigenetic instability in sperm.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666335X23000496/pdfft?md5=43c638c46631220e714347868ce6e311&pid=1-s2.0-S2666335X23000496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316832","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}
To develop a spatiotemporal model for de prediction of euploid and aneuploid embryos using time-lapse videos from 10–115 hours after insemination (hpi).
Design
Retrospective study.
Main Outcome Measures
The research used an end-to-end approach to develop an automated artificial intelligence system capable of extracting features from images and classifying them, considering spatiotemporal dependencies. A convolutional neural network extracted the most relevant features from each video frame. A bidirectional long short-term memory layer received this information and analyzed the temporal dependencies, obtaining a low-dimensional feature vector that characterized each video. A multilayer perceptron classified them into 2 groups, euploid and noneuploid.
Results
The model performance in accuracy fell between 0.6170 and 0.7308. A multi-input model with a gate recurrent unit module performed better than others; the precision (or positive predictive value) is 0.8205 for predicting euploidy. Sensitivity, specificity, F1-Score and accuracy are 0.6957, 0.7813, 0.7042, and 0.7308, respectively.
Conclusions
This article proposes an artificial intelligence solution for prioritizing euploid embryo transfer. We can highlight the identification of a noninvasive method for chromosomal status diagnosis using a deep learning approach that analyzes raw data provided by time-lapse incubators. This method demonstrated potential automation of the evaluation process, allowing spatial and temporal information to encode.
{"title":"Deep learning system for classification of ploidy status using time-lapse videos","authors":"Elena Paya M.Sc. , Cristian Pulgarín M.Sc. , Lorena Bori M.Sc. , Adrián Colomer Ph.D. , Valery Naranjo Ph.D. , Marcos Meseguer Ph.D.","doi":"10.1016/j.xfss.2023.06.002","DOIUrl":"10.1016/j.xfss.2023.06.002","url":null,"abstract":"<div><h3>Objective</h3><p>To develop a spatiotemporal model for de prediction of euploid and aneuploid<span> embryos using time-lapse videos from 10–115 hours after insemination (hpi).</span></p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Main Outcome Measures</h3><p>The research used an end-to-end approach to develop an automated artificial intelligence system capable of extracting features from images and classifying them, considering spatiotemporal dependencies. A convolutional neural network extracted the most relevant features from each video frame. A bidirectional long short-term memory layer received this information and analyzed the temporal dependencies, obtaining a low-dimensional feature vector that characterized each video. A multilayer perceptron classified them into 2 groups, euploid and noneuploid.</p></div><div><h3>Results</h3><p>The model performance in accuracy fell between 0.6170 and 0.7308. A multi-input model with a gate recurrent unit module performed better than others; the precision (or positive predictive value) is 0.8205 for predicting euploidy. Sensitivity, specificity, F1-Score and accuracy are 0.6957, 0.7813, 0.7042, and 0.7308, respectively.</p></div><div><h3>Conclusions</h3><p>This article proposes an artificial intelligence solution for prioritizing euploid embryo transfer. We can highlight the identification of a noninvasive method for chromosomal status diagnosis using a deep learning approach that analyzes raw data provided by time-lapse incubators. This method demonstrated potential automation of the evaluation process, allowing spatial and temporal information to encode.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393453","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.05.003
Mohamed Ali Ph.D. , David Stone M.D. , Archana Laknaur Ph.D. , Qiwei Yang Ph.D. , Ayman Al-Hendy M.D., Ph.D.
Objective
To investigate the link between EZH2 and Wnt/β-catenin signaling and its role in uterine fibroids (UFs) pathogenesis and explore the potential effect of natural compound methyl jasmonate (MJ) against UFs.
Design
EZH2 overexpression or inhibition was achieved in human uterine leiomyoma (HuLM) cells using EZH2-expressing adenovirus or chemical EZH2 inhibitor (DZNep), respectively. The HuLM and normal uterine smooth muscle cells were treated with 0.1–3 mM of MJ, and several experiments were employed.
Setting
Laboratory study.
Patients(s)
None.
Intervention(s)
Methyl jasmonate.
Main Outcome Measure(s)
Protein expression of EZH2, β-catenin, and proliferating cell nuclear antigen (PCNA) was measured by Western blot as well as gene expression alterations of Wnt ligands (Wnt5A, Wnt5b, and Wnt9A), WISP1, CTNNB1, and its responsive gene PITX2 using quantitative real-time polymerase chain reaction. The protein and ribonucleic acid (RNA) levels of several markers were measured in MJ-treated or untreated HuLM cells, including EZH2 and β-catenin, extracellular matrix markers collagen type 1 (COL1A1) and fibronectin (FN), proliferation markers cyclin D1 (CCND1) and PCNA, tumor suppressor marker p21, and apoptotic markers (BAX, cytochrome c, and cleaved caspase 3).
Result(s)
EZH2 overexpression significantly increased the gene expression of several Wnt ligands (PITX2, WISP1, WNT5A, WNT5B, and WNT9A), which increased nuclear translocation of β-catenin and PCNA and eventually HuLM cell proliferation. EZH2 inhibition blocked Wnt/β-catenin signaling activation where the aforementioned genes significantly decreased as well as PCNA, cyclin D1, and PITX2 protein expression compared with those in untreated HuLM. Methyl jasmonate showed a potent antiproliferative effect on HuLM cells in a dose- and time-dependent manner. Interestingly, the dose range (0.1–0.5 mM) showed a selective growth inhibitory effect on HuLM cells, not on normal uterine smooth muscle cells. Methyl jasmonate treatment at 0.5 mM for 24 hours significantly decreased both protein and RNA levels of EZH2, β-catenin, COL1A1, FN, CCND1, PCNA, WISP1, and PITX2 but increased the protein levels of p21, BAX, cytochrome, c and cleaved caspase 3 compared with untreated HuLM. Methyl jasmonate–treated cells exhibited down-regulation in the RNA expression of 36 genes, including CTNNB1, CCND1, Wnt5A, Wnt5B, and Wnt9A, and up-regulation in the expression of 34 genes, including Wnt antagonist genes WIF1, PRICKlE1, and DKK1 compared with control, confirming the quantitative real-time polymerase chain reaction results.
{"title":"EZH2 activates Wnt/β-catenin signaling in human uterine fibroids, which is inhibited by the natural compound methyl jasmonate","authors":"Mohamed Ali Ph.D. , David Stone M.D. , Archana Laknaur Ph.D. , Qiwei Yang Ph.D. , Ayman Al-Hendy M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.003","DOIUrl":"10.1016/j.xfss.2023.05.003","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the link between EZH2 and Wnt/β-catenin signaling and its role in uterine fibroids (UFs) pathogenesis and explore the potential effect of natural compound methyl jasmonate (MJ) against UFs.</p></div><div><h3>Design</h3><p>EZH2 overexpression or inhibition was achieved in human uterine leiomyoma (HuLM) cells using EZH2-expressing adenovirus or chemical EZH2 inhibitor (DZNep), respectively. The HuLM and normal uterine smooth muscle cells were treated with 0.1–3 mM of MJ, and several experiments were employed.</p></div><div><h3>Setting</h3><p>Laboratory study.</p></div><div><h3>Patients(s)</h3><p>None.</p></div><div><h3>Intervention(s)</h3><p>Methyl jasmonate.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Protein expression of EZH2, β-catenin, and proliferating cell nuclear antigen (PCNA) was measured by Western blot as well as gene expression alterations of Wnt ligands (<em>Wnt5A</em>, <em>Wnt5b</em>, and <em>Wnt9A</em>), <em>WISP1</em>, <em>CTNNB1</em>, and its responsive gene <em>PITX2</em> using quantitative real-time polymerase chain reaction. The protein and ribonucleic acid (RNA) levels of several markers were measured in MJ-treated or untreated HuLM cells, including EZH2 and β-catenin, extracellular matrix markers collagen type 1 (COL1A1) and fibronectin (FN), proliferation markers cyclin D1 (CCND1) and PCNA, tumor suppressor marker p21, and apoptotic markers (BAX, cytochrome c, and cleaved caspase 3).</p></div><div><h3>Result(s)</h3><p>EZH2 overexpression significantly increased the gene expression of several Wnt ligands (<em>PITX2</em>, <em>WISP1</em>, <em>WNT5A</em>, <em>WNT5B</em>, and <em>WNT9A</em>), which increased nuclear translocation of β-catenin and PCNA and eventually HuLM cell proliferation. EZH2 inhibition blocked Wnt/β-catenin signaling activation where the aforementioned genes significantly decreased as well as PCNA, cyclin D1, and PITX2 protein expression compared with those in untreated HuLM. Methyl jasmonate showed a potent antiproliferative effect on HuLM cells in a dose- and time-dependent manner. Interestingly, the dose range (0.1–0.5 mM) showed a selective growth inhibitory effect on HuLM cells, not on normal uterine smooth muscle cells. Methyl jasmonate treatment at 0.5 mM for 24 hours significantly decreased both protein and RNA levels of EZH2, β-catenin, COL1A1, FN, CCND1, PCNA, WISP1, and PITX2 but increased the protein levels of p21, BAX, cytochrome, c and cleaved caspase 3 compared with untreated HuLM. Methyl jasmonate–treated cells exhibited down-regulation in the RNA expression of 36 genes, including <em>CTNNB1</em>, <em>CCND1</em>, <em>Wnt5A</em>, <em>Wnt5B</em>, and <em>Wnt9A</em>, and up-regulation in the expression of 34 genes, including Wnt antagonist genes <em>WIF1</em>, <em>PRICKlE1</em>, and DKK1 compared with control, confirming the quantitative real-time polymerase chain reaction results.</p></div><div><h3>Conclusion(s)</h3><p>Our studies provide a novel lin","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151011","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.04.003
Linda B.P.M. Stevens Brentjens M.D., M.Sc. , Darina Obukhova M.Sc. , Janneke E. den Hartog M.D., Ph.D. , Bert Delvoux M.Sc. , Johanna Koskivuori M.Sc. , Seppo Auriola Prof. , Merja R. Häkkinen Ph.D. , Bich N. Bui M.D. , Nienke E. van Hoogenhuijze M.D., Ph.D. , Shari Mackens M.D., Prof. , Femke Mol M.D., Ph.D. , Jan Peter de Bruin M.D., Ph.D. , Dagmar Besselink M.D. , Gijs Teklenburg M.D., Ph.D , Viktorija Kukushkina M.Sc. , Andres Salumets Prof. , Frank J.M. Broekmans M.D., Prof. , Ron J.T. van Golde M.D., Ph.D. , Masoud Zamani Esteki Ph.D. , Andrea Romano Ph.D.
Objective
To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients.
Design
Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after “endometrial scratching.” Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle.
Setting
University hopsital.
Patients
Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age.
Intervention
None.
Main Outcome Measure(s)
Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change >|0.5| were selected as the threshold for differentially expressed genes.
Result(s)
Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including HSD11B2, that catalyzes the conversion of cortisol into cortisone.
Conclusion(s)
Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity.
{"title":"An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients","authors":"Linda B.P.M. Stevens Brentjens M.D., M.Sc. , Darina Obukhova M.Sc. , Janneke E. den Hartog M.D., Ph.D. , Bert Delvoux M.Sc. , Johanna Koskivuori M.Sc. , Seppo Auriola Prof. , Merja R. Häkkinen Ph.D. , Bich N. Bui M.D. , Nienke E. van Hoogenhuijze M.D., Ph.D. , Shari Mackens M.D., Prof. , Femke Mol M.D., Ph.D. , Jan Peter de Bruin M.D., Ph.D. , Dagmar Besselink M.D. , Gijs Teklenburg M.D., Ph.D , Viktorija Kukushkina M.Sc. , Andres Salumets Prof. , Frank J.M. Broekmans M.D., Prof. , Ron J.T. van Golde M.D., Ph.D. , Masoud Zamani Esteki Ph.D. , Andrea Romano Ph.D.","doi":"10.1016/j.xfss.2023.04.003","DOIUrl":"10.1016/j.xfss.2023.04.003","url":null,"abstract":"<div><h3>Objective</h3><p>To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients.</p></div><div><h3>Design</h3><p>Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after “endometrial scratching.” Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle.</p></div><div><h3>Setting</h3><p>University hopsital.</p></div><div><h3>Patients</h3><p>Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age.</p></div><div><h3>Intervention</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change >|0.5| were selected as the threshold for differentially expressed genes.</p></div><div><h3>Result(s)</h3><p>Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including <em>HSD11B2</em>, that catalyzes the conversion of cortisol into cortisone.</p></div><div><h3>Conclusion(s)</h3><p>Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity.</p></div><div><h3>Clinical Trial Registration Number</h3><p>The study","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10411060","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.05.001
Rhayza Roberta Andretta Ph.D. , Letícia Signori de Castro Ph.D. , Renata Cristina de Carvalho M.Sc. , Jheysson Alfredo Cordeiro de Moura M.Sc. , Renato Fraietta Ph.D. , Fatima Kazue Okada Ph.D. , Ricardo Pimenta Bertolla Ph.D.
Objective
To study the relationship between the seminal sample quality of men with varicocele and sperm capacitation.
Design
Cross-sectional observational study.
Setting
Academic hospital.
Patient(s)
Seventy-six men (19 control and 57 with varicocele) were analyzed.
Intervention(s)
Semen samples were submitted to a discontinuous density gradient for sperm selection. Sperm capacitation was induced using a human tubal fluid medium supplemented with bovine serum albumin.
Main Outcome Measure(s)
After capacitation induction, the sperm were assessed by capacitation state, computer-assisted sperm motility, mitochondrial activity, membrane integrity, acrosome reaction, and intracellular oxidative stress.
Result(s)
The capacitation period increased sperm motility, showing an increase in the average path velocity and a decrease in the straightness compared with sperm before capacitation (paired analysis). After capacitation, the rate of capacitated sperm, motility, and mitochondrial activity showed differences between groups (control and varicocele). The varicocele group showed lower mitochondrial activity and capacitation than the control group. On the other hand, no significant differences were observed in the other variables evaluated.
Conclusion(s)
Varicocele men showed less viable sperm and mitochondrial activity than control men after capacitation sperm. The induction of capacitation altered motility by increasing path velocity and decreasing straightness in all of the studied groups, evidencing the occurrence of hyperactivation.
{"title":"Understanding the impact of varicocele on sperm capacitation","authors":"Rhayza Roberta Andretta Ph.D. , Letícia Signori de Castro Ph.D. , Renata Cristina de Carvalho M.Sc. , Jheysson Alfredo Cordeiro de Moura M.Sc. , Renato Fraietta Ph.D. , Fatima Kazue Okada Ph.D. , Ricardo Pimenta Bertolla Ph.D.","doi":"10.1016/j.xfss.2023.05.001","DOIUrl":"10.1016/j.xfss.2023.05.001","url":null,"abstract":"<div><h3>Objective</h3><p><span>To study the relationship between the seminal sample quality of men with varicocele and </span>sperm capacitation.</p></div><div><h3>Design</h3><p>Cross-sectional observational study.</p></div><div><h3>Setting</h3><p>Academic hospital.</p></div><div><h3>Patient(s)</h3><p>Seventy-six men (19 control and 57 with varicocele) were analyzed.</p></div><div><h3>Intervention(s)</h3><p>Semen samples were submitted to a discontinuous density gradient for sperm selection. Sperm capacitation was induced using a human tubal fluid medium supplemented with bovine serum albumin.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>After capacitation induction, the sperm were assessed by capacitation state, computer-assisted sperm motility, mitochondrial activity, membrane integrity, </span>acrosome reaction<span>, and intracellular oxidative stress.</span></p></div><div><h3>Result(s)</h3><p>The capacitation period increased sperm motility, showing an increase in the average path velocity and a decrease in the straightness compared with sperm before capacitation (paired analysis). After capacitation, the rate of capacitated sperm, motility, and mitochondrial activity showed differences between groups (control and varicocele). The varicocele group showed lower mitochondrial activity and capacitation than the control group. On the other hand, no significant differences were observed in the other variables evaluated.</p></div><div><h3>Conclusion(s)</h3><p>Varicocele men showed less viable sperm and mitochondrial activity than control men after capacitation sperm. The induction of capacitation altered motility by increasing path velocity and decreasing straightness in all of the studied groups, evidencing the occurrence of hyperactivation.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10036779","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.05.005
Maurizio Mauro Ph.D. , Shan Wei Ph.D. , Andrzej Breborowicz M.D. , Xin Li Ph.D. , Claudia Bognanni Ph.D. , Zachary Fuller Ph.D. , Thomas Philipp M.D. , Torrin McDonald Ph.D. , Miriam Temmeh Lattin B.A. , Zev Williams M.D., Ph.D.
Objective
To determine the mechanistic role of mobile genetic elements in causing widespread DNA damage in primary human trophoblasts.
Design
Experimental ex vivo study.
Setting
Hospital-affiliated University.
Patient(s)
Trophoblasts from a patient with unexplained recurrent pregnancy loss and patients with spontaneous and elective abortions (n = 10).
Intervention(s)
Biochemical and genetic analysis and modification of primary human trophoblasts.
Main Outcome Measure(s)
To phenotype and systematically evaluate the underlying pathogenic mechanism for elevated DNA damage observed in trophoblasts derived from a patient with unexplained recurrent pregnancy loss, transcervical embryoscopy, G-band karyotyping, RNA sequencing, quantitative polymerase chain reaction, immunoblotting, biochemical and siRNA assays, and whole-genome sequencing were performed.
Result(s)
Transcervical embryoscopy revealed a severely dysmorphic embryo that was euploid on G-band karyotyping. RNA sequencing was notable for markedly elevated LINE-1 expression, confirmed with quantitative polymerase chain reaction, and that resulted in elevated expression of LINE-1-encoded proteins, as shown by immunoblotting. Immunofluorescence, biochemical and genetic approaches demonstrated that overexpression of LINE-1 caused reversible widespread genomic damage and apoptosis.
Conclusion(s)
Derepression of LINE-1 elements in early trophoblasts results in reversible but widespread DNA damage.
{"title":"Endogenous retrotransposons cause catastrophic deoxyribonucleic acid damage in human trophoblasts","authors":"Maurizio Mauro Ph.D. , Shan Wei Ph.D. , Andrzej Breborowicz M.D. , Xin Li Ph.D. , Claudia Bognanni Ph.D. , Zachary Fuller Ph.D. , Thomas Philipp M.D. , Torrin McDonald Ph.D. , Miriam Temmeh Lattin B.A. , Zev Williams M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.005","DOIUrl":"10.1016/j.xfss.2023.05.005","url":null,"abstract":"<div><h3>Objective</h3><p>To determine the mechanistic role of mobile genetic elements in causing widespread DNA damage in primary human trophoblasts.</p></div><div><h3>Design</h3><p>Experimental ex vivo study.</p></div><div><h3>Setting</h3><p>Hospital-affiliated University.</p></div><div><h3>Patient(s)</h3><p><span>Trophoblasts from a patient with unexplained recurrent pregnancy loss and patients with spontaneous and </span>elective abortions (n = 10).</p></div><div><h3>Intervention(s)</h3><p>Biochemical and genetic analysis and modification of primary human trophoblasts.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>To phenotype and systematically evaluate the underlying pathogenic mechanism for elevated DNA damage observed in trophoblasts derived from a patient with unexplained recurrent pregnancy loss, transcervical embryoscopy, G-band karyotyping, </span>RNA sequencing<span>, quantitative polymerase chain reaction, immunoblotting<span>, biochemical and siRNA assays, and whole-genome sequencing were performed.</span></span></p></div><div><h3>Result(s)</h3><p>Transcervical embryoscopy revealed a severely dysmorphic embryo that was euploid on G-band karyotyping. RNA sequencing was notable for markedly elevated LINE-1 expression, confirmed with quantitative polymerase chain reaction, and that resulted in elevated expression of LINE-1-encoded proteins, as shown by immunoblotting. Immunofluorescence<span>, biochemical and genetic approaches demonstrated that overexpression of LINE-1 caused reversible widespread genomic damage and apoptosis.</span></p></div><div><h3>Conclusion(s)</h3><p>Derepression of LINE-1 elements in early trophoblasts results in reversible but widespread DNA damage.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038945","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.07.002
William H. Catherino M.D., Ph.D. (Editor-in-Chief, Fertility and Sterility - Science)
{"title":"From the Editor-in-Chief","authors":"William H. Catherino M.D., Ph.D. (Editor-in-Chief, Fertility and Sterility - Science)","doi":"10.1016/j.xfss.2023.07.002","DOIUrl":"10.1016/j.xfss.2023.07.002","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018793","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 : 2023-08-01DOI: 10.1016/j.xfss.2023.05.002
Jialin Zou M.D. , Tianxiang Ni M.D., Ph.D. , Min Yang M.D. , Hongchang Li M.D., Ph.D. , Ming Gao M.D., Ph.D. , Yueting Zhu M.D., Ph.D. , Wenjie Jiang M.D., Ph.D. , Qian Zhang M.D., Ph.D. , Junhao Yan M.D., Ph.D. , Daimin Wei M.D., Ph.D. , Zi-Jiang Chen M.D., Ph.D.
Objective
To evaluate whether the effect of de novo mutated balanced reciprocal translocation on the rate of euploid embryos varied from inherited balanced reciprocal translocation.
Design
A retrospective cohort study compared the percentage of euploid embryo and proportion of patients with at least 1 euploid embryo between de novo mutated balanced reciprocal translocation (i.e., the group of de novo mutated carriers) and inherited balanced reciprocal translocation (i.e., the group of inherited carriers).
Setting
An academic fertility center.
Patient(s)
A total of 413 couples with balanced reciprocal translocation (219 female carriers and 194 male carriers) who underwent their first cycle of preimplantation genetic testing for structural rearrangements were included.
Intervention(s)
Carriers of balanced reciprocal translocation either de novo mutated or inherited.
Main Outcome Measure(s)
The percentage of euploid embryo and proportion of patients with at least 1 euploid embryo.
Result(s)
The carriers of the de novo mutated balanced reciprocal translocation had a lower percentage of euploid embryos (19.5% vs. 25.5%), and were less likely to have at least 1 euploid embryo (47.1% vs. 60.1%) compared with the carriers of the inherited balanced reciprocal translocation. In the male-carrier subgroup, the percentage of euploid embryos (16.7% vs. 26.7%) and proportion of patients with at least 1 euploid embryo (41.9% vs. 67.5%) were lower among the de novo mutated carriers than those among the inherited carriers. However, in the female-carrier subgroup, there was no statistically significant difference in the percentage of euploid embryos (22.4% vs. 24.4%) or the proportion of patients with at least 1 euploid embryo (52.3% vs. 53.7%) between the de novo mutated carriers and inherited carriers.
Conclusion(s)
The de novo mutated balanced reciprocal translocation was associated with a lower percentage of euploid embryos and lower chance of obtaining at least 1 euploid embryo than the inherited balanced reciprocal translocation.
{"title":"The effect of parental carrier of de novo mutated vs. inherited balanced reciprocal translocation on the chance of euploid embryos","authors":"Jialin Zou M.D. , Tianxiang Ni M.D., Ph.D. , Min Yang M.D. , Hongchang Li M.D., Ph.D. , Ming Gao M.D., Ph.D. , Yueting Zhu M.D., Ph.D. , Wenjie Jiang M.D., Ph.D. , Qian Zhang M.D., Ph.D. , Junhao Yan M.D., Ph.D. , Daimin Wei M.D., Ph.D. , Zi-Jiang Chen M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.002","DOIUrl":"10.1016/j.xfss.2023.05.002","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate whether the effect of de novo mutated balanced reciprocal translocation on the rate of euploid embryos varied from inherited balanced reciprocal translocation.</p></div><div><h3>Design</h3><p>A retrospective cohort study compared the percentage of euploid embryo and proportion of patients with at least 1 euploid embryo between de novo mutated balanced reciprocal translocation (i.e., the group of de novo mutated carriers) and inherited balanced reciprocal translocation (i.e., the group of inherited carriers).</p></div><div><h3>Setting</h3><p>An academic fertility center.</p></div><div><h3>Patient(s)</h3><p>A total of 413 couples with balanced reciprocal translocation (219 female carriers and 194 male carriers) who underwent their first cycle of preimplantation genetic testing for structural rearrangements were included.</p></div><div><h3>Intervention(s)</h3><p>Carriers of balanced reciprocal translocation either de novo mutated or inherited.</p></div><div><h3>Main Outcome Measure(s)</h3><p>The percentage of euploid embryo and proportion of patients with at least 1 euploid embryo.</p></div><div><h3>Result(s)</h3><p>The carriers of the de novo mutated balanced reciprocal translocation had a lower percentage of euploid embryos (19.5% vs. 25.5%), and were less likely to have at least 1 euploid embryo (47.1% vs. 60.1%) compared with the carriers of the inherited balanced reciprocal translocation. In the male-carrier subgroup, the percentage of euploid embryos (16.7% vs. 26.7%) and proportion of patients with at least 1 euploid embryo (41.9% vs. 67.5%) were lower among the de novo mutated carriers than those among the inherited carriers. However, in the female-carrier subgroup, there was no statistically significant difference in the percentage of euploid embryos (22.4% vs. 24.4%) or the proportion of patients with at least 1 euploid embryo (52.3% vs. 53.7%) between the de novo mutated carriers and inherited carriers.</p></div><div><h3>Conclusion(s)</h3><p>The de novo mutated balanced reciprocal translocation was associated with a lower percentage of euploid embryos and lower chance of obtaining at least 1 euploid embryo than the inherited balanced reciprocal translocation.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10033990","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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