Pub Date : 2024-06-25DOI: 10.1101/2024.06.25.24309475
Romy Cappenberg, Jesus Garcia Garcia, Christine Happle, Anna Zychlinsky Scharff
Background Dysphoric Milk Ejection Reflex (DMER), which affects a significant proportion of lactating parents and may significantly impact feeding choices, is poorly understood.
背景 对很多哺乳期父母都会出现的排乳反射障碍(DMER)知之甚少,它可能会严重影响喂养选择。
{"title":"Dysphoric Milk Ejection Reflex: Risk, Prevalence, and Persistence","authors":"Romy Cappenberg, Jesus Garcia Garcia, Christine Happle, Anna Zychlinsky Scharff","doi":"10.1101/2024.06.25.24309475","DOIUrl":"https://doi.org/10.1101/2024.06.25.24309475","url":null,"abstract":"<strong>Background</strong> Dysphoric Milk Ejection Reflex (DMER), which affects a significant proportion of lactating parents and may significantly impact feeding choices, is poorly understood.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"206 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512600","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 : 2024-06-25DOI: 10.1101/2024.06.25.24309408
Elleke F. Bosma, Brynjulf Mortensen, Kevin DeLong, Mads Roepke, Helene Baek Juel, Randi Rich, Amalie Axelsen, Marouschka Scheeper, Rasmus Marvig, Thomas Gundelund Rasmussen, Colleen Acosta, Ulrich Binne, Anne Bloch Thomsen, Hans-Christian Ingerslev, Fareeha Zulfiqar, Tine Wroending, Paul Cotter, Marcus O'Brien, Shriram Patel, Sarita Dam, Julia Albert Nicholson, Henriette Svarre Nielsen, Timothy Dinan, Fergus McCarthy, Johan E.T. van Hylckama Vlieg, Laura M. Ensign
Here, we describe the first placebo-controlled trial of vaginal microbiota transplantation (VMT) in women with asymptomatic dysbiosis without the use of antibiotic pretreatment. Importantly, we also describe the implementation of a donor program and banking of donor cervicovaginal secretions (CVS) while retaining sample viability, which is crucial to allow for scale-up and confirmatory quality testing. By metagenome sequencing, we demonstrate that VMT provided a significant increase in combined Lactobacillus species in the active arm and strain-level genetic analysis confirmed Lactobacillus engraftment. Moreover, VMT was well tolerated and showed a good safety profile. Furthermore, a shift toward increased Lactobacillus was associated with a change in the expression profile of genes in the complement pathway to a more anti-inflammatory profile. Vaginal microbial and immune profile restoration using VMT may have a positive impact on a wide range of conditions in womens health.
{"title":"Antibiotic-free vaginal microbiota transplantation (VMT) changes vaginal microbiota and immune profile in women with asymptomatic dysbiosis: reporting of a randomized, placebo-controlled trial","authors":"Elleke F. Bosma, Brynjulf Mortensen, Kevin DeLong, Mads Roepke, Helene Baek Juel, Randi Rich, Amalie Axelsen, Marouschka Scheeper, Rasmus Marvig, Thomas Gundelund Rasmussen, Colleen Acosta, Ulrich Binne, Anne Bloch Thomsen, Hans-Christian Ingerslev, Fareeha Zulfiqar, Tine Wroending, Paul Cotter, Marcus O'Brien, Shriram Patel, Sarita Dam, Julia Albert Nicholson, Henriette Svarre Nielsen, Timothy Dinan, Fergus McCarthy, Johan E.T. van Hylckama Vlieg, Laura M. Ensign","doi":"10.1101/2024.06.25.24309408","DOIUrl":"https://doi.org/10.1101/2024.06.25.24309408","url":null,"abstract":"Here, we describe the first placebo-controlled trial of vaginal microbiota transplantation (VMT) in women with asymptomatic dysbiosis without the use of antibiotic pretreatment. Importantly, we also describe the implementation of a donor program and banking of donor cervicovaginal secretions (CVS) while retaining sample viability, which is crucial to allow for scale-up and confirmatory quality testing. By metagenome sequencing, we demonstrate that VMT provided a significant increase in combined Lactobacillus species in the active arm and strain-level genetic analysis confirmed Lactobacillus engraftment. Moreover, VMT was well tolerated and showed a good safety profile. Furthermore, a shift toward increased Lactobacillus was associated with a change in the expression profile of genes in the complement pathway to a more anti-inflammatory profile. Vaginal microbial and immune profile restoration using VMT may have a positive impact on a wide range of conditions in womens health.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505957","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 : 2024-06-21DOI: 10.1101/2024.06.20.24308970
Elizabeth T. Nguyen, Matthew G. Retzloff, Laura April Gago, John E. Nichols, John F. Payne, Barry A. Ripps, Michael Opsahl, Jeremy Groll, Ronald Beesley, Lorie Nowak, Gregory Neal, Jaye Adams, Trevor Swanson, Xiaocong Chen, Mylene W. M. Yao
Objective: To compare the performance of machine learning based, center-specific (MLCS) models and the US national registry-based, multicenter model (SART model) in predicting IVF live birth probabilities (LBPs) for 6 unrelated, geographically diverse US fertility centers. Design: Retrospective observational design. Subjects: Test sets comprised first IVF cycle data (2013-2022) extracted from a retrospective cohort of 4,645 patients at 6 fertility centers. Intervention or Exposure: The initial (MLCS1) and updated (MLCS2) models were compared against age control. MLSC2 and SART models were compared. Main Outcome Measures: Model validation metrics, reported in median and interquartile range (IQR), were compared using Wilcoxon signed-rank test: ROC AUC, posterior log-likelihood of odds ratio compared to age (PLORA), Precision-Recall (PR) AUC, F1 score and continuous net reclassification improvement (NRI). Results: MLCS1 and MLCS2 models showed improved AUC and PLORA compared to age control; MLCS1 models were validated using out-of-time test data. MLCS2 models showed improved PLORA 23.9 (IQR 10.2, 39.4) compared to 7.2 (IQR 3.6, 11.8) for MLCS1, p<0.05. MLCS2 showed higher median PR AUC at 0.75 (IQR 0.73, 0.77) compared to 0.69 (IQR 0.68, 0.71) for SART, p<0.05. In addition, the median F1 Score was higher for MLCS2 compared to SART model across predicted live birth probability (LBP) thresholds sampled at deciles at ≥40%, ≥50%, ≥60%, ≥70%. For example, at the 50% LBP threshold, MLCS2 had a median F1 score of 0.74 (IQR 0.72, 0.78) compared to 0.71 (IQR 0.68, 0.73) for SART. At these six centers, using the LBP threshold of ≥ 50%, MLCS2 models can identify ~84% of patients who would go on to have IVF live births, while the SART model can only identify ~75%. That means for every 100 patients who will have a first IVF cycle live birth, using LBR ≥ 50% as threshold, the MLCS2 model can identify 9 more such patients without overcalling or overestimating LBPs compared to the SART model. Conclusion: MLCS models accurately assign higher IVF LBPs to more patients compared to the SART model at 6 US fertility centers. We recommend testing a larger sample of fertility centers to evaluate generalizability of MLCS model benefits.
{"title":"Predicting IVF live birth probabilities using machine learning, center-specific and national registry-based models","authors":"Elizabeth T. Nguyen, Matthew G. Retzloff, Laura April Gago, John E. Nichols, John F. Payne, Barry A. Ripps, Michael Opsahl, Jeremy Groll, Ronald Beesley, Lorie Nowak, Gregory Neal, Jaye Adams, Trevor Swanson, Xiaocong Chen, Mylene W. M. Yao","doi":"10.1101/2024.06.20.24308970","DOIUrl":"https://doi.org/10.1101/2024.06.20.24308970","url":null,"abstract":"Objective:\u0000To compare the performance of machine learning based, center-specific (MLCS) models and the US national registry-based, multicenter model (SART model) in predicting IVF live birth probabilities (LBPs) for 6 unrelated, geographically diverse US fertility centers. Design:\u0000Retrospective observational design. Subjects:\u0000Test sets comprised first IVF cycle data (2013-2022) extracted from a retrospective cohort of 4,645 patients at 6 fertility centers. Intervention or Exposure:\u0000The initial (MLCS1) and updated (MLCS2) models were compared against age control. MLSC2 and SART models were compared. Main Outcome Measures:\u0000Model validation metrics, reported in median and interquartile range (IQR), were compared using Wilcoxon signed-rank test: ROC AUC, posterior log-likelihood of odds ratio compared to age (PLORA), Precision-Recall (PR) AUC, F1 score and continuous net reclassification improvement (NRI). Results:\u0000MLCS1 and MLCS2 models showed improved AUC and PLORA compared to age control; MLCS1 models were validated using out-of-time test data. MLCS2 models showed improved PLORA 23.9 (IQR 10.2, 39.4) compared to 7.2 (IQR 3.6, 11.8) for MLCS1, p<0.05. MLCS2 showed higher median PR AUC at 0.75 (IQR 0.73, 0.77) compared to 0.69 (IQR 0.68, 0.71) for SART, p<0.05. In addition, the median F1 Score was higher for MLCS2 compared to SART model across predicted live birth probability (LBP) thresholds sampled at deciles at ≥40%, ≥50%, ≥60%, ≥70%. For example, at the 50% LBP threshold, MLCS2 had a median F1 score of 0.74 (IQR 0.72, 0.78) compared to 0.71 (IQR 0.68, 0.73) for SART. At these six centers, using the LBP threshold of ≥ 50%, MLCS2 models can identify ~84% of patients who would go on to have IVF live births, while the SART model can only identify ~75%. That means for every 100 patients who will have a first IVF cycle live birth, using LBR ≥ 50% as threshold, the MLCS2 model can identify 9 more such patients without overcalling or overestimating LBPs compared to the SART model. Conclusion:\u0000MLCS models accurately assign higher IVF LBPs to more patients compared to the SART model at 6 US fertility centers. We recommend testing a larger sample of fertility centers to evaluate generalizability of MLCS model benefits.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506016","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}