Pub Date : 2024-05-12DOI: 10.1016/j.rbmo.2024.104108
Research question
Is the microRNA miR-145 involved in adenomyosis, and by what mechanisms does it affect disease development and is itself regulated?
Design
Fluorescence in-situ hybridization was used to observe the expression pattern of miR-145 in adenomyosis ectopic endometrium (n = 13), adenomyosis eutopic endometrium (n = 15) and non-adenomyosis eutopic endometrium (n = 14). RNA sequencing was used to screen target genes as well as downstream pathways of miR-145, which were validated by reporter gene assay, quantitative polymerase chain reaction and western blot, and further analysed using cell migration assay and chromatin immunoprecipitation assay.
Results
The fluorescence in-situ hybridization assay revealed a noteworthy elevation in miR-145 expression in adenomyosis tissue compared with non-adenomyosis tissue. Furthermore, RNA sequencing analysis revealed that overexpression of miR-145 resulted in heightened expression of genes associated with the cytokine signalling pathway, nucleotide-binding and oligomerization domain-like pathway and adhesion pathway, including IL-1β and IL-6. Our study has identified CITED2 as a downstream direct target gene of miR-145, which is implicated in the inhibition of stromal cell migration induced by miR-145. Moreover, chromatin immunoprecipitation was used to validate the direct effect of oestradiol on the promoter region of miR-145, mediated by oestrogen receptor α, which facilitates the upregulation of miR-145 expression.
Conclusion
Our findings provide evidence supporting the role of oestradiol, acting through its receptor α, in modulating the discovered miR-145-CITED2 signalling axis, thereby promoting the progression of adenomyosis.
{"title":"Oestrogen promotes the progression of adenomyosis by inhibiting CITED2 through miR-145","authors":"","doi":"10.1016/j.rbmo.2024.104108","DOIUrl":"10.1016/j.rbmo.2024.104108","url":null,"abstract":"<div><h3>Research question</h3><p>Is the microRNA miR-145 involved in adenomyosis, and by what mechanisms does it affect disease development and is itself regulated?</p></div><div><h3>Design</h3><p>Fluorescence in-situ hybridization was used to observe the expression pattern of miR-145 in adenomyosis ectopic endometrium (<em>n</em> = 13), adenomyosis eutopic endometrium (<em>n</em> = 15) and non-adenomyosis eutopic endometrium (<em>n</em> = 14). RNA sequencing was used to screen target genes as well as downstream pathways of miR-145, which were validated by reporter gene assay, quantitative polymerase chain reaction and western blot, and further analysed using cell migration assay and chromatin immunoprecipitation assay.</p></div><div><h3>Results</h3><p>The fluorescence in-situ hybridization assay revealed a noteworthy elevation in miR-145 expression in adenomyosis tissue compared with non-adenomyosis tissue. Furthermore, RNA sequencing analysis revealed that overexpression of miR-145 resulted in heightened expression of genes associated with the cytokine signalling pathway, nucleotide-binding and oligomerization domain-like pathway and adhesion pathway, including <em>IL-1β</em> and <em>IL-6</em>. Our study has identified <em>CITED2</em> as a downstream direct target gene of miR-145, which is implicated in the inhibition of stromal cell migration induced by miR-145. Moreover, chromatin immunoprecipitation was used to validate the direct effect of oestradiol on the promoter region of miR-145, mediated by oestrogen receptor α, which facilitates the upregulation of miR-145 expression.</p></div><div><h3>Conclusion</h3><p>Our findings provide evidence supporting the role of oestradiol, acting through its receptor α, in modulating the discovered miR-145-CITED2 signalling axis, thereby promoting the progression of adenomyosis.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 6","pages":"Article 104108"},"PeriodicalIF":3.7,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141051812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1016/j.rbmo.2024.104107
Research question
Does the application of a micro-dose of copper chloride gel increase endometrial production of vascular endothelial growth factor (VEGF) without compromising endometrial function or producing embryo toxicity?
Design
An estimate of optimal dose was made based on cell culture studies. Ten healthy participants received an initial uterine application of placebo gel, followed by copper chloride gel (37.5 μM, 75 μM, or 150 μM dose) in a later hormone replacement cycle. Endometrial biopsies (day 5.5 luteal) and pelvic ultrasound were carried out during each cycle to evaluate endometrial function and growth. Uterine fluid was assessed for residual copper levels on the day of biopsy, and copper chloride gel underwent mouse embryos assay assessment for potential embryo toxicity.
Results
The copper gel significantly increased endometrial VEGF expression (quantitative polymerase chain reaction), and also increasing endometrial thickness by an average of 2.2 mm compared with matched control cycles. The copper gel did not adversely affect endometrial morphology or maturation (histological dating and molecular receptivity testing), and mouse embryos assay studies showed no evidence of embryo toxicity. Furthermore, uterine cavity flush samples mostly lacked copper, with only negligible amounts present in one sample.
Conclusion
Applying copper chloride gel to the uterine cavity upregulated endometrial VEGF and significantly increased endometrial thickness and volume. No adverse effects on the endometrium or embryos were observed. Copper chloride gels show promise for treating suboptimal endometrial thickness if the results of this study are confirmed by larger randomized controlled trials.
{"title":"Effect of a novel copper chloride gel on endometrial growth and function in healthy volunteers","authors":"","doi":"10.1016/j.rbmo.2024.104107","DOIUrl":"10.1016/j.rbmo.2024.104107","url":null,"abstract":"<div><h3>Research question</h3><p>Does the application of a micro-dose of copper chloride gel increase endometrial production of vascular endothelial growth factor (VEGF) without compromising endometrial function or producing embryo toxicity?</p></div><div><h3>Design</h3><p>An estimate of optimal dose was made based on cell culture studies. Ten healthy participants received an initial uterine application of placebo gel, followed by copper chloride gel (37.5 μM, 75 μM, or 150 μM dose) in a later hormone replacement cycle. Endometrial biopsies (day 5.5 luteal) and pelvic ultrasound were carried out during each cycle to evaluate endometrial function and growth. Uterine fluid was assessed for residual copper levels on the day of biopsy, and copper chloride gel underwent mouse embryos assay assessment for potential embryo toxicity.</p></div><div><h3>Results</h3><p>The copper gel significantly increased endometrial VEGF expression (quantitative polymerase chain reaction), and also increasing endometrial thickness by an average of 2.2 mm compared with matched control cycles. The copper gel did not adversely affect endometrial morphology or maturation (histological dating and molecular receptivity testing), and mouse embryos assay studies showed no evidence of embryo toxicity. Furthermore, uterine cavity flush samples mostly lacked copper, with only negligible amounts present in one sample.</p></div><div><h3>Conclusion</h3><p>Applying copper chloride gel to the uterine cavity upregulated endometrial VEGF and significantly increased endometrial thickness and volume. No adverse effects on the endometrium or embryos were observed. Copper chloride gels show promise for treating suboptimal endometrial thickness if the results of this study are confirmed by larger randomized controlled trials.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 4","pages":"Article 104107"},"PeriodicalIF":3.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472648324002967/pdfft?md5=6fd6ffe22a36dbd396e6a56c64b06d73&pid=1-s2.0-S1472648324002967-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1016/j.rbmo.2024.104077
Research question
Does luteal phase support (LPS) with oral progesterone improve the live birth rate (LBR) in patients undergoing intrauterine insemination (IUI) cycles with letrozole?
Design
This retrospective cohort study included 1199 IUI cycles with letrozole between January 2017 and December 2021. A nearest neighbour random matching approach was employed to pair the LPS group and the control group in a 1:2 ratio. Eight variables were chosen for matching in the propensity score matching (PSM) model: age; body mass index; duration of infertility; cause(s) of infertility; antral follicle count; basal concentration of FSH; rank of IUI attempts; and leading follicle size. LBR was selected as the primary outcome.
Results
In total, 427 LPS cycles were matched with 772 non-LPS (control) cycles after PSM. The LBR was significantly higher in the LPS group compared with the control group (19.7% versus 14.5%; P = 0.0255). The clinical pregnancy rate (23.2% versus 17.6%; P = 0.0245) and ongoing pregnancy rate (20.6% versus 15.8%; P = 0.0437) were also significantly higher in the LPS group. The biochemical pregnancy rate, ectopic pregnancy rate and miscarriage rate were similar in the two groups (P > 0.05). The intergroup comparison revealed no significant variances in terms of gestational age, mode of delivery, ectopic pregnancy rate or abortion rate. Furthermore, there were no significant differences in birth weight or birth length between the two groups.
Conclusions
Luteal support with oral progesterone significantly improved the LBR in IUI cycles with letrozole, but did not affect neonatal outcomes.
{"title":"Luteal phase support with oral progesterone improves live birth rate in intrauterine insemination cycles using letrozole","authors":"","doi":"10.1016/j.rbmo.2024.104077","DOIUrl":"10.1016/j.rbmo.2024.104077","url":null,"abstract":"<div><h3>Research question</h3><p>Does luteal phase support (LPS) with oral progesterone improve the live birth rate (LBR) in patients undergoing intrauterine insemination (IUI) cycles with letrozole?</p></div><div><h3>Design</h3><p>This retrospective cohort study included 1199 IUI cycles with letrozole between January 2017 and December 2021. A nearest neighbour random matching approach was employed to pair the LPS group and the control group in a 1:2 ratio. Eight variables were chosen for matching in the propensity score matching (PSM) model: age; body mass index; duration of infertility; cause(s) of infertility; antral follicle count; basal concentration of FSH; rank of IUI attempts; and leading follicle size. LBR was selected as the primary outcome.</p></div><div><h3>Results</h3><p>In total, 427 LPS cycles were matched with 772 non-LPS (control) cycles after PSM. The LBR was significantly higher in the LPS group compared with the control group (19.7% versus 14.5%; P = 0.0255). The clinical pregnancy rate (23.2% versus 17.6%; P = 0.0245) and ongoing pregnancy rate (20.6% versus 15.8%; P = 0.0437) were also significantly higher in the LPS group. The biochemical pregnancy rate, ectopic pregnancy rate and miscarriage rate were similar in the two groups (P > 0.05). The intergroup comparison revealed no significant variances in terms of gestational age, mode of delivery, ectopic pregnancy rate or abortion rate. Furthermore, there were no significant differences in birth weight or birth length between the two groups.</p></div><div><h3>Conclusions</h3><p>Luteal support with oral progesterone significantly improved the LBR in IUI cycles with letrozole, but did not affect neonatal outcomes.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 4","pages":"Article 104077"},"PeriodicalIF":3.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141054657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1016/j.rbmo.2024.104105
Carlos Hernandez-Nieto , Saher Siddiqui , Loreli Mejia-Fernandez , Tamar Alkon-Meadows , Joseph Lee , Richard Slifkin , Tanmoy Mukherjee , Alan B. Copperman
Research question
Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)?
Design
This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulus–oocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts.
Results
A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (n = 84); IUD, levonorgestrel low dose (<52 mg) (n = 37); IUD, levonorgestrel (n = 192); subdermal etonogestrel implant (n = 14); injectable medroxyprogesterone acetate (n = 11); etonogestrel vaginal ring (n = 142); combined oral contraceptive pills (n = 2349); and norelgestromin transdermal patch (n = 10). The control group included patients not using contraceptives or using barrier or calendar methods (n = 1220). Among all the cohorts the median number of cumulus–oocyte complexes retrieved during oocyte retrieval was comparable (P = 0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (P = 0.03, P < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation.
Conclusions
Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC.
{"title":"Effect of various contraceptives on oocyte yield and maturation in patients undergoing planned oocyte cryopreservation","authors":"Carlos Hernandez-Nieto , Saher Siddiqui , Loreli Mejia-Fernandez , Tamar Alkon-Meadows , Joseph Lee , Richard Slifkin , Tanmoy Mukherjee , Alan B. Copperman","doi":"10.1016/j.rbmo.2024.104105","DOIUrl":"10.1016/j.rbmo.2024.104105","url":null,"abstract":"<div><h3>Research question</h3><p>Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)?</p></div><div><h3>Design</h3><p>This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulus–oocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts.</p></div><div><h3>Results</h3><p>A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (<em>n</em> = 84); IUD, levonorgestrel low dose (<52 mg) (<em>n</em> = 37); IUD, levonorgestrel (<em>n</em> = 192); subdermal etonogestrel implant (<em>n</em> = 14); injectable medroxyprogesterone acetate (<em>n</em> = 11); etonogestrel vaginal ring (<em>n</em> = 142); combined oral contraceptive pills (<em>n</em> = 2349); and norelgestromin transdermal patch (<em>n</em> = 10). The control group included patients not using contraceptives or using barrier or calendar methods (<em>n</em> = 1220). Among all the cohorts the median number of cumulus–oocyte complexes retrieved during oocyte retrieval was comparable (<em>P</em> = 0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (<em>P</em> = 0.03, <em>P</em> < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation.</p></div><div><h3>Conclusions</h3><p>Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104105"},"PeriodicalIF":3.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1016/j.rbmo.2024.104103
Research question
Does double blastocyst vitrification and warming affect pregnancy, miscarriage or live birth rates, or birth outcomes, from embryos that have undergone preimplantation genetic testing for aneuploidies (PGT-A) testing?
Design
This retrospective observational analysis of embryo transfers was performed at a single centre between January 2017 and August 2022. The double-vitrification group included frozen blastocysts that were vitrified after 5–7 days of culture, warmed, biopsied (either once or twice) and re-vitrified. The single vitrification (SV) group included fresh blastocysts that were biopsied at 5–7 days and then vitrified.
Results
A comparison of the 84 double-vitrification blastocysts and 729 control single-vitrification blastocysts indicated that the double-vitrification embryos were frozen later in development and had expanded more than the single-vitrification embryos. Of the 813 embryo transfer procedures reported, 452 resulted in the successful delivery of healthy infants (56%). There were no significant differences between double-vitrification and single-vitrification embryos in the pregnancy, miscarriage or live birth rates achieved after single-embryo transfer (55% versus 56%). Logistic regression indicated that while reduced live birth rates were associated with increasing maternal age at oocyte collection, longer culture prior to freezing and lower embryo quality, double vitrification was not a significant predictor of live birth rate.
Conclusions
Blastocyst double vitrification was not shown to impact pregnancy, miscarriage or live birth rates. Although caution is necessary due to the study size, no effects of double vitrification on miscarriage rates, birthweight or gestation period were noted. These data offer reassurance given the absence of the influence of double vitrification on all outcomes after PGT-A.
{"title":"Double vitrification and warming of blastocysts does not affect pregnancy, miscarriage or live birth rates","authors":"","doi":"10.1016/j.rbmo.2024.104103","DOIUrl":"10.1016/j.rbmo.2024.104103","url":null,"abstract":"<div><h3>Research question</h3><p>Does double blastocyst vitrification and warming affect pregnancy, miscarriage or live birth rates, or birth outcomes, from embryos that have undergone preimplantation genetic testing for aneuploidies (PGT-A) testing?</p></div><div><h3>Design</h3><p>This retrospective observational analysis of embryo transfers was performed at a single centre between January 2017 and August 2022. The double-vitrification group included frozen blastocysts that were vitrified after 5–7 days of culture, warmed, biopsied (either once or twice) and re-vitrified. The single vitrification (SV) group included fresh blastocysts that were biopsied at 5–7 days and then vitrified.</p></div><div><h3>Results</h3><p>A comparison of the 84 double-vitrification blastocysts and 729 control single-vitrification blastocysts indicated that the double-vitrification embryos were frozen later in development and had expanded more than the single-vitrification embryos. Of the 813 embryo transfer procedures reported, 452 resulted in the successful delivery of healthy infants (56%). There were no significant differences between double-vitrification and single-vitrification embryos in the pregnancy, miscarriage or live birth rates achieved after single-embryo transfer (55% versus 56%). Logistic regression indicated that while reduced live birth rates were associated with increasing maternal age at oocyte collection, longer culture prior to freezing and lower embryo quality, double vitrification was not a significant predictor of live birth rate.</p></div><div><h3>Conclusions</h3><p>Blastocyst double vitrification was not shown to impact pregnancy, miscarriage or live birth rates. Although caution is necessary due to the study size, no effects of double vitrification on miscarriage rates, birthweight or gestation period were noted. These data offer reassurance given the absence of the influence of double vitrification on all outcomes after PGT-A.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104103"},"PeriodicalIF":3.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1016/j.rbmo.2024.104078
Research question
Does hyperandrogenaemia affect the function of ovarian granulosa cells by activating ferroptosis, and could this process be regulated by endoplasmic reticulum stress?
Design
Levels of ferroptosis and endoplasmic reticulum stress in granulosa cells were detected in women with and without polycystic ovary syndrome (PCOS) undergoing IVF. Ferroptosis and endoplasmic reticulum stress levels of ovarian tissue and follicle development were detected in control mice and PCOS-like mice models, induced by dehydroepiandrosterone. An in-vitro PCOS model of KGN cells was constructed with testosterone and ferroptosis inhibitor Fer-1. Endoplasmic reticulum stress inhibitor, tauroursodeoxycholate (TUDCA), determined the potential mechanism associated with excessive induction of ferroptosis in granulosa cells related to PCOS, and levels of ferroptosis and endoplasmic reticulum stress were detected.
Results
Activation of ferroptosis and endoplasmic reticulum stress occurred in granulosa cells of women with PCOS and the varies of PCOS-like mice. The findings in KGN cells demonstrated that testosterone treatment results in elevation of oxidative stress levels, particularly lipid peroxidation, and intracellular iron accumulation in granulosa cells. The expression of genes and proteins associated with factors related to ferroptosis, mitochondrial membrane potential and ultrastructure showed that testosterone activated ferroptosis, whereas Fer-1 reversed these alterations. During in-vitro experiments, activation of endoplasmic reticulum stress induced by testosterone treatment was detected in granulosa cells. In granulosa cells, TUDCA, an inhibitor of endoplasmic reticulum stress, significantly mitigated testosterone-induced ferroptosis.
Conclusions
Ferroptosis plays a part in reproductive injury mediated by hyperandrogens associated with PCOS, and may be regulated by endoplasmic reticulum stress.
{"title":"Endoplasmic reticulum stress-mediated ferroptosis in granulosa cells contributes to follicular dysfunction of polycystic ovary syndrome driven by hyperandrogenism","authors":"","doi":"10.1016/j.rbmo.2024.104078","DOIUrl":"10.1016/j.rbmo.2024.104078","url":null,"abstract":"<div><h3>Research question</h3><p>Does hyperandrogenaemia affect the function of ovarian granulosa cells by activating ferroptosis, and could this process be regulated by endoplasmic reticulum stress?</p></div><div><h3>Design</h3><p>Levels of ferroptosis and endoplasmic reticulum stress in granulosa cells were detected in women with and without polycystic ovary syndrome (PCOS) undergoing IVF. Ferroptosis and endoplasmic reticulum stress levels of ovarian tissue and follicle development were detected in control mice and PCOS-like mice models, induced by dehydroepiandrosterone. An in-vitro PCOS model of KGN cells was constructed with testosterone and ferroptosis inhibitor Fer-1. Endoplasmic reticulum stress inhibitor, tauroursodeoxycholate (TUDCA), determined the potential mechanism associated with excessive induction of ferroptosis in granulosa cells related to PCOS, and levels of ferroptosis and endoplasmic reticulum stress were detected.</p></div><div><h3>Results</h3><p>Activation of ferroptosis and endoplasmic reticulum stress occurred in granulosa cells of women with PCOS and the varies of PCOS-like mice. The findings in KGN cells demonstrated that testosterone treatment results in elevation of oxidative stress levels, particularly lipid peroxidation, and intracellular iron accumulation in granulosa cells. The expression of genes and proteins associated with factors related to ferroptosis, mitochondrial membrane potential and ultrastructure showed that testosterone activated ferroptosis, whereas Fer-1 reversed these alterations. During in-vitro experiments, activation of endoplasmic reticulum stress induced by testosterone treatment was detected in granulosa cells. In granulosa cells, TUDCA, an inhibitor of endoplasmic reticulum stress, significantly mitigated testosterone-induced ferroptosis.</p></div><div><h3>Conclusions</h3><p>Ferroptosis plays a part in reproductive injury mediated by hyperandrogens associated with PCOS, and may be regulated by endoplasmic reticulum stress.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104078"},"PeriodicalIF":3.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472648324002670/pdfft?md5=69ada9461d673236b6edf83867fe1033&pid=1-s2.0-S1472648324002670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.1016/j.rbmo.2024.104102
Clinical embryology is a dynamic and ever-evolving field, and as such clinical practice guidelines must be regularly reviewed and updated. Accordingly, this document supersedes previous good clinical practice in clinical embryology guidance, developing, and updating where necessary, existing good practice guidelines. The Association of Reproductive and Clinical Scientists (ARCS) suggests this Good Laboratory Practice framework as appropriate and effective to ensure the best possible care for all individuals undertaking fertility treatment. Efforts have been made to ensure that the language used is inclusive and reflective of the wide range of patients who seek treatment. The guidance provided within this document aims to be relevant within an international context and to consider the range of regulatory considerations affecting clinical embryology laboratories. This guideline was written to guide best practice but is not intended as a tool to judge the practice of centres within the UK or beyond.
临床胚胎学是一个不断发展的动态领域,因此临床实践指南必须定期审查和更新。因此,本文件取代了之前的临床胚胎学良好临床实践指南,发展并在必要时更新了现有的良好实践指南。生殖与临床科学家协会 (Association of Reproductive and Clinical Scientists, ARCS) 建议,本良好实验室实践框架是适当而有效的,可确保为所有接受生育治疗的人提供最佳护理。我们努力确保所使用的语言具有包容性,并能反映出寻求治疗的患者的广泛性。本文件中提供的指导旨在与国际背景相关,并考虑到影响临床胚胎学实验室的一系列监管因素。编写本指南的目的是为了指导最佳实践,但并不打算将其作为评判英国境内外各中心实践的工具。
{"title":"Good practice in clinical embryology laboratories: Association of Reproductive and Clinical Scientists Guidelines 2024","authors":"","doi":"10.1016/j.rbmo.2024.104102","DOIUrl":"10.1016/j.rbmo.2024.104102","url":null,"abstract":"<div><div>Clinical embryology is a dynamic and ever-evolving field, and as such clinical practice guidelines must be regularly reviewed and updated. Accordingly, this document supersedes previous good clinical practice in clinical embryology guidance, developing, and updating where necessary, existing good practice guidelines. The Association of Reproductive and Clinical Scientists (ARCS) suggests this Good Laboratory Practice framework as appropriate and effective to ensure the best possible care for all individuals undertaking fertility treatment. Efforts have been made to ensure that the language used is inclusive and reflective of the wide range of patients who seek treatment. The guidance provided within this document aims to be relevant within an international context and to consider the range of regulatory considerations affecting clinical embryology laboratories. This guideline was written to guide best practice but is not intended as a tool to judge the practice of centres within the UK or beyond.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 6","pages":"Article 104102"},"PeriodicalIF":3.7,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141037385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
What is the attitude of Belgian women of reproductive age towards enucleated egg donation? Does the willingness of women to donate differ when they would donate enucleated or whole eggs?
Design
In 2022, an online survey was conducted among a representative sample of 1000 women in Belgium aged 18–50 years. The item on willingness to anonymously donate enucleated eggs was dichotomized into those willing to donate and those not willing to donate or uncertain.
Results
No statistically significant difference was found between the willingness to donate enucleated eggs and whole eggs (whether anonymously or identifiably). Anonymity, however, affected the willingness to donate, with considerably fewer women willing to donate identifiably. The respondents were divided about their parental status if they were to donate enucleated eggs, with less than one-half (44%) not considering themselves to be a genetic mother. Women willing to donate enucleated eggs anonymously were less likely to view themselves as a genetic mother of the child compared with others. Fewer than one in five considered the technique unacceptable because the resulting child would carry genetic material of three persons.
Conclusions
Women in the general population did not show a greater willingness to donate enucleated eggs than whole eggs. The fact that the respondents were strongly divided on whether or not they would consider themselves to be a genetic mother of the resulting child may explain this result. Other factors, such as the potential high risk for the child, may also have contributed to less willingness.
{"title":"Attitude of Belgian women towards enucleated egg donation for treatment of mitochondrial diseases and infertility","authors":"Guido Pennings , Björn Heindryckx , Dominic Stoop , Heidi Mertes","doi":"10.1016/j.rbmo.2024.104101","DOIUrl":"10.1016/j.rbmo.2024.104101","url":null,"abstract":"<div><h3>Research question</h3><p>What is the attitude of Belgian women of reproductive age towards enucleated egg donation? Does the willingness of women to donate differ when they would donate enucleated or whole eggs?</p></div><div><h3>Design</h3><p>In 2022, an online survey was conducted among a representative sample of 1000 women in Belgium aged 18–50 years. The item on willingness to anonymously donate enucleated eggs was dichotomized into those willing to donate and those not willing to donate or uncertain.</p></div><div><h3>Results</h3><p>No statistically significant difference was found between the willingness to donate enucleated eggs and whole eggs (whether anonymously or identifiably). Anonymity, however, affected the willingness to donate, with considerably fewer women willing to donate identifiably. The respondents were divided about their parental status if they were to donate enucleated eggs, with less than one-half (44%) not considering themselves to be a genetic mother. Women willing to donate enucleated eggs anonymously were less likely to view themselves as a genetic mother of the child compared with others. Fewer than one in five considered the technique unacceptable because the resulting child would carry genetic material of three persons.</p></div><div><h3>Conclusions</h3><p>Women in the general population did not show a greater willingness to donate enucleated eggs than whole eggs. The fact that the respondents were strongly divided on whether or not they would consider themselves to be a genetic mother of the resulting child may explain this result. Other factors, such as the potential high risk for the child, may also have contributed to less willingness.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104101"},"PeriodicalIF":3.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-04DOI: 10.1016/j.rbmo.2024.104104
Research question
Does the co-transfer of a good-quality embryo and a poor-quality embryo influence pregnancy outcomes in comparison to the transfer of a single good-quality embryo in vitrified-warmed blastocyst transfer cycles?
Design
This retrospective cohort study involved a total of 11,738 women who underwent IVF/intracytoplasmic sperm injection cycles and vitrified-warmed blastocyst transfer at a tertiary-care academic medical from January 2015 to June 2022. The study population was categorized into two groups: single-blastocyst transfer (SBT; participants who underwent single good-quality embryo transfer, n = 9338) versus double-blastocyst transfer (DBT; participants who underwent transfers with a poor and a good-quality embryo, n = 2400).
Results
The live birth rate (LBR) was significantly higher in the DBT group in comparison with the SBT group (65.6% versus 56.3%, P < 0.001). Multivariable logistic regression analysis showed that DBT was an independent predictor for LBR with a strong potential impact (adjusted odds ratio 1.55, 95% confidence interval 1.41–1.71; P < 0.001). However, the multiple birth rate was significantly higher in the good-quality embryo and poor-quality embryo group compared with patients undergoing a single good-quality embryo transfer (41.4% versus 1.8%; P < 0.001).
Conclusions
In vitrified-warmed blastocyst transfer cycles, LBR was higher following DBT with one good-quality and one poor-quality embryo compared with SBT. However, this was at the expense of a marked increase in the likelihood of multiple gestations. Physicians should still balance the benefits and risks of double-embryo transfer.
{"title":"Impact of inclusion of a poor-quality embryo with a good-quality embryo on pregnancy outcomes in vitrified-warmed blastocyst transfers","authors":"","doi":"10.1016/j.rbmo.2024.104104","DOIUrl":"10.1016/j.rbmo.2024.104104","url":null,"abstract":"<div><h3>Research question</h3><p>Does the co-transfer of a good-quality embryo and a poor-quality embryo influence pregnancy outcomes in comparison to the transfer of a single good-quality embryo in vitrified-warmed blastocyst transfer cycles?</p></div><div><h3>Design</h3><p>This retrospective cohort study involved a total of 11,738 women who underwent IVF/intracytoplasmic sperm injection cycles and vitrified-warmed blastocyst transfer at a tertiary-care academic medical from January 2015 to June 2022. The study population was categorized into two groups: single-blastocyst transfer (SBT; participants who underwent single good-quality embryo transfer, <em>n</em> = 9338) versus double-blastocyst transfer (DBT; participants who underwent transfers with a poor and a good-quality embryo, <em>n</em> = 2400).</p></div><div><h3>Results</h3><p>The live birth rate (LBR) was significantly higher in the DBT group in comparison with the SBT group (65.6% versus 56.3%, <em>P</em> < 0.001). Multivariable logistic regression analysis showed that DBT was an independent predictor for LBR with a strong potential impact (adjusted odds ratio 1.55, 95% confidence interval 1.41–1.71; <em>P</em> < 0.001). However, the multiple birth rate was significantly higher in the good-quality embryo and poor-quality embryo group compared with patients undergoing a single good-quality embryo transfer (41.4% versus 1.8%; <em>P</em> < 0.001).</p></div><div><h3>Conclusions</h3><p>In vitrified-warmed blastocyst transfer cycles, LBR was higher following DBT with one good-quality and one poor-quality embryo compared with SBT. However, this was at the expense of a marked increase in the likelihood of multiple gestations. Physicians should still balance the benefits and risks of double-embryo transfer.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104104"},"PeriodicalIF":3.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1016/j.rbmo.2024.104100
Maha Eid , Adrien Lemoine , Lena Bardet , Lise Selleret , Sophie Stout , Emmanuelle Mathieu d'Argent , Anna Ly , Nathalie Sermondade , Cyril Touboul , Charlotte Dupont , Nathalie Chabbert-Buffet , Kamila Kolanska
Research question
Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF?
Design
This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS).
Results
Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; P < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m2 versus 24.6 ± 4.4 kg/m2; P < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; P = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; P = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, P < 0.001; 16% versus 25%, P = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; P = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06–5.15; P = 0.039).
Conclusion
Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result.
{"title":"Pain after oocyte retrieval in women with endometriosis undergoing fertility preservation or IVF","authors":"Maha Eid , Adrien Lemoine , Lena Bardet , Lise Selleret , Sophie Stout , Emmanuelle Mathieu d'Argent , Anna Ly , Nathalie Sermondade , Cyril Touboul , Charlotte Dupont , Nathalie Chabbert-Buffet , Kamila Kolanska","doi":"10.1016/j.rbmo.2024.104100","DOIUrl":"10.1016/j.rbmo.2024.104100","url":null,"abstract":"<div><h3>Research question</h3><p>Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF?</p></div><div><h3>Design</h3><p>This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (<em>n</em> = 401) or IVF (<em>n</em> = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS).</p></div><div><h3>Results</h3><p>Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; <em>P</em> < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m<sup>2</sup> versus 24.6 ± 4.4 kg/m<sup>2</sup>; <em>P</em> < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; <em>P</em> = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; <em>P</em> = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, <em>P</em> < 0.001; 16% versus 25%, <em>P</em> = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; <em>P</em> = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06–5.15; <em>P</em> = 0.039).</p></div><div><h3>Conclusion</h3><p>Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"49 3","pages":"Article 104100"},"PeriodicalIF":3.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141027838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}