Pub Date : 2024-03-01DOI: 10.1097/01.ogx.0001010448.83325.67
Erping Long, Jianzhi Zhang
The antagonistic pleiotropy hypothesis is one of the leading theories in the evolutionary origin of aging. It states that mutations contributing to aging could be positively selected for if they are advantageous early in life and promote earlier reproduction or more offspring. The evidence supporting the antagonistic pleiotropy hypothesis in humans is mixed and lacks unambiguous genome-wide support. The UK Biobank contains the genotypes and various phenotypes of 500,000 participants, offering an opportunity to test the antagonistic pleiotropy hypothesis in humans. This analysis aimed to use the UK Biobank to determine whether genetic variants influencing reproduction are likely to affect lifespan, whether pleiotropy between reproduction and lifespan are largely antagonistic, and whether pleiotropic mutations promoting reproduction but causing aging are favored by natural selection. In addition, potential molecular mechanisms linking reproduction to aging were investigated. Genetic correlation between 2 phenotypic traits was defined as the proportion of variance that the 2 traits share due to genetic causes and is a measure of the contribution of pleiotropy to the covariation of the traits. Four reproductive traits were focused on negative age at first birth, negative age at first sex, number of children fathers, and age at menopause, with larger values of these traits corresponding to higher reproduction. Two life span traits were examined: father's age at death and mother's age at death. Data were available for a total of 276,406 UK Biobank participants, and 583 genetic variants were reported to be associated with at least 1 reproductive trait. A strong, negative genetic correlation was observed between the 3 reproductive traits and 2 life span traits, supporting the antagonistic pleiotropy hypothesis. Individuals ranked in the top third in polygenic score (PGS) for the 3 reproductive traits had a significantly lower probability of survival to age 76 (SV76) than that of individuals ranked in the bottom third. Compared with randomly selected polymorphisms, those impacting reproduction were 5 times more likely to affect life span and 7.5 times more likely to affect life span antagonistically. Among individuals with the same number of children ever born, SV76 was negatively correlated with the PGS for each of the 4 reproductive traits. In this study, the evidence shows a strong negative genetic correlation between reproduction and parental life span, as well as between parental reproduction and parental life span. This supports the antagonistic pleiotropy hypothesis of aging in humans.
{"title":"Evidence for the Role of Selection for Reproductively Advantageous Alleles in Human Aging","authors":"Erping Long, Jianzhi Zhang","doi":"10.1097/01.ogx.0001010448.83325.67","DOIUrl":"https://doi.org/10.1097/01.ogx.0001010448.83325.67","url":null,"abstract":"\u0000 The antagonistic pleiotropy hypothesis is one of the leading theories in the evolutionary origin of aging. It states that mutations contributing to aging could be positively selected for if they are advantageous early in life and promote earlier reproduction or more offspring. The evidence supporting the antagonistic pleiotropy hypothesis in humans is mixed and lacks unambiguous genome-wide support. The UK Biobank contains the genotypes and various phenotypes of 500,000 participants, offering an opportunity to test the antagonistic pleiotropy hypothesis in humans.\u0000 This analysis aimed to use the UK Biobank to determine whether genetic variants influencing reproduction are likely to affect lifespan, whether pleiotropy between reproduction and lifespan are largely antagonistic, and whether pleiotropic mutations promoting reproduction but causing aging are favored by natural selection. In addition, potential molecular mechanisms linking reproduction to aging were investigated. Genetic correlation between 2 phenotypic traits was defined as the proportion of variance that the 2 traits share due to genetic causes and is a measure of the contribution of pleiotropy to the covariation of the traits. Four reproductive traits were focused on negative age at first birth, negative age at first sex, number of children fathers, and age at menopause, with larger values of these traits corresponding to higher reproduction. Two life span traits were examined: father's age at death and mother's age at death.\u0000 Data were available for a total of 276,406 UK Biobank participants, and 583 genetic variants were reported to be associated with at least 1 reproductive trait. A strong, negative genetic correlation was observed between the 3 reproductive traits and 2 life span traits, supporting the antagonistic pleiotropy hypothesis. Individuals ranked in the top third in polygenic score (PGS) for the 3 reproductive traits had a significantly lower probability of survival to age 76 (SV76) than that of individuals ranked in the bottom third. Compared with randomly selected polymorphisms, those impacting reproduction were 5 times more likely to affect life span and 7.5 times more likely to affect life span antagonistically. Among individuals with the same number of children ever born, SV76 was negatively correlated with the PGS for each of the 4 reproductive traits. In this study, the evidence shows a strong negative genetic correlation between reproduction and parental life span, as well as between parental reproduction and parental life span. This supports the antagonistic pleiotropy hypothesis of aging in humans.","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"437 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140281850","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 : 2024-03-01DOI: 10.1097/01.ogx.0001010440.77705.9e
R. Winer, John Lin, Melissa L. Anderson, Jasmin A Tiro, Beverly B Green, Hongyuan Gao, R. Meenan, Kristina Hansen, Angela Sparks, Diana S. M. Buist
In the United States, adherence for cervical cancer screening decreased from 86% to 77% between 2005 and 2019. Over 50% of cervical cancers are diagnosed in individuals overdue for screening, and promoting access and adherence is essential. Unlike traditional Papanicolaou testing, human papillomavirus (HPV) screening can use self-collected samples, which have comparable sensitivity and specificity to clinician-collected samples. Self-collecting has been shown to increase screening adherence, possibly by circumventing important barriers such as scheduling clinic appointments and negativity about pelvic examinations. Despite this, most individuals in prior studies remained unscreened with low follow-up of HPV-positive results, and kit uptake among populations that are screening adherent or have unknown screening history is unknown. The STEP trial (self-testing options in the era for primary HPV screening for cervical cancer) was a parallel, single-blind, randomized clinical trial comparing cervical cancer screening completion across groups of individuals with due (screening-adherent), overdue, or unknown screening history. Participants were randomized to traditional care (patient reminders and clinician electronic health record [HER] alerts), education (usual care plus educational materials about screening), direct mail (traditional care plus educational materials plus a mailed HPV self-collection kit), or to opt in (traditional care plus educational materials plus the option to request a self-collection kit). Patients were identified using the Kaiser Permanente Washington HER and administrative claims. Eligible participants were females aged 30 to 64 years with current Kaiser Permanente Washington insurance and primary care, intact cervix, who were either due or overdue for screening. The primary study outcome was screening completion within 6 months after randomization, which could be done either in clinic or using the self-collection kit. Modified Poisson regression was used to estimate relative risk (RR) of screening completion for the direct-mail and opt-in groups, relative to the education group. A total of 32,771 participants were randomized between November 2020 and January 2022, of which 13,356 were due for screening, 8682 were overdue, and 10,733 had unknown screening history. Of those due for screening, the RR for screening completion was 1.30 (95% confidence interval [CI], 1.23–1.36; absolute difference, 14.1% [95% CI, 11.2%–16.9%]) for direct mail and 1.07 (95% CI, 1.02–1.12; absolute difference, 3.5% [95% CI, 1.2%–5.7%]) for the opt-in group compared with education. Of those overdue for screening, the RR for screening completion was 1.90 (95% CI, 1.68–2.16; absolute difference 16.9% [95% CI, 13.8%–20.0%]) for direct mail compared with education. Of those with unknown screening history, the RR for screening completion was 1.14 (95% CI, 1.03–1.25; absolute difference 2.2% [95% CI, 0.5%–3.9%]) for the opt-in group compared with educa
{"title":"Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial","authors":"R. Winer, John Lin, Melissa L. Anderson, Jasmin A Tiro, Beverly B Green, Hongyuan Gao, R. Meenan, Kristina Hansen, Angela Sparks, Diana S. M. Buist","doi":"10.1097/01.ogx.0001010440.77705.9e","DOIUrl":"https://doi.org/10.1097/01.ogx.0001010440.77705.9e","url":null,"abstract":"\u0000 In the United States, adherence for cervical cancer screening decreased from 86% to 77% between 2005 and 2019. Over 50% of cervical cancers are diagnosed in individuals overdue for screening, and promoting access and adherence is essential. Unlike traditional Papanicolaou testing, human papillomavirus (HPV) screening can use self-collected samples, which have comparable sensitivity and specificity to clinician-collected samples. Self-collecting has been shown to increase screening adherence, possibly by circumventing important barriers such as scheduling clinic appointments and negativity about pelvic examinations. Despite this, most individuals in prior studies remained unscreened with low follow-up of HPV-positive results, and kit uptake among populations that are screening adherent or have unknown screening history is unknown.\u0000 The STEP trial (self-testing options in the era for primary HPV screening for cervical cancer) was a parallel, single-blind, randomized clinical trial comparing cervical cancer screening completion across groups of individuals with due (screening-adherent), overdue, or unknown screening history. Participants were randomized to traditional care (patient reminders and clinician electronic health record [HER] alerts), education (usual care plus educational materials about screening), direct mail (traditional care plus educational materials plus a mailed HPV self-collection kit), or to opt in (traditional care plus educational materials plus the option to request a self-collection kit). Patients were identified using the Kaiser Permanente Washington HER and administrative claims. Eligible participants were females aged 30 to 64 years with current Kaiser Permanente Washington insurance and primary care, intact cervix, who were either due or overdue for screening. The primary study outcome was screening completion within 6 months after randomization, which could be done either in clinic or using the self-collection kit. Modified Poisson regression was used to estimate relative risk (RR) of screening completion for the direct-mail and opt-in groups, relative to the education group.\u0000 A total of 32,771 participants were randomized between November 2020 and January 2022, of which 13,356 were due for screening, 8682 were overdue, and 10,733 had unknown screening history. Of those due for screening, the RR for screening completion was 1.30 (95% confidence interval [CI], 1.23–1.36; absolute difference, 14.1% [95% CI, 11.2%–16.9%]) for direct mail and 1.07 (95% CI, 1.02–1.12; absolute difference, 3.5% [95% CI, 1.2%–5.7%]) for the opt-in group compared with education. Of those overdue for screening, the RR for screening completion was 1.90 (95% CI, 1.68–2.16; absolute difference 16.9% [95% CI, 13.8%–20.0%]) for direct mail compared with education. Of those with unknown screening history, the RR for screening completion was 1.14 (95% CI, 1.03–1.25; absolute difference 2.2% [95% CI, 0.5%–3.9%]) for the opt-in group compared with educa","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"60 s2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272166","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 : 2024-03-01DOI: 10.1097/ogx.0000000000001254
P. Verdyck, G. Altarescu, S. Santos-Ribeiro, C. Vrettou, U. Koehler, G. Griesinger, V. Goossens, C. Magli, C. Albanese, M. Parriego, L. Coll, R. Ron-El, K. Sermon, J. Traeger-Synodinos
Many chromosome abnormalities are commonly observed and can lead to early pregnancy loss, miscarriage, or the birth of children with chromosomal defects. Such abnormalities are considered a major factor in the low pregnancy rate after assisted reproductive technology and natural conception. Preimplantation genetic testing for aneuploidy (PGT-A) aims to minimize the transfer of aneuploid embryos. Embryonic aneuploidies arising from errors in meiosis have an incidence of approximately 25% in embryos from women younger than 35 years, to more than half in embryos from women aged older than 35 years. Although these embryos are able to develop to the blastocyst stage, they tend to be of lower morphological quality. A recent multicenter randomized clinical trial (ESTEEM) analyzed polar bodies (PBs) from women after intracytoplasmic sperm injection aged between 36 and 40 years using microarrays in 205 cycles and found that the transfer of embryos from euploid oocytes did not lead to a higher live birth rate but was associated with a reduction in the number of embryo transfers and miscarriages. This study aimed to evaluate all PB results from this RCT and characterize the types of chromosomal abnormalities and the chromosomes most frequently affected. The ESTEEM trial obtained biopsy of first (PB1) and second (PB2) PB in the cohort receiving PGT-A and analyzed them using array comparative genomic hybridization (aCGH). A total of 693 PB pairs had full results available, including 676 confirmed fertilized oocytes. Chromosome segregations, including likely underlying mechanisms, from these pairs are reported here. To estimate the reliability of the aCGH procedure, 72 PB pairs from a single center were reanalyzed using next-generation sequencing (NGS). Embryos were classified into 4 categories based on morphology: good, fair, poor, and degenerated. A comparative analysis was performed to assess the association between chromosome status and embryo quality as well as study group (PGT-A vs control) and embryo quality. A total of 213/676 oocytes were euploid and 413/676 were aneuploid, whereas in the remaining 50 oocytes, an abnormality observed in PB1 was compensated by an abnormality in PB2. A total of 693 PB pairs reported chromatic numbers with results for 15,939 chromosomes. An abnormal segregation, in PB1 and/or PB2, was observed in 1162 chromosomes (7.3%) in 461 PB pairs. Chromosomes 22 (16.7%), 16 (16.6%), 19 (14.4%), 21 (13.7%), and 15 (12.4%) had the highest frequencies for abnormal segregations. The abnormal segregations were compatible with precocious separation of sister chromatids in meiosis 1 (M1) (n = 568; 48.9%), nondisjunction of chromatics in meiosis 2 (M2) or reverse segregation (n = 417; 35.9%), and nondisjunction in M1 (n = 65; 5.6%). However, 112 chromosomes had segregation patterns that could not be categorized into 1 of the 9 known mechanisms causing aneuploidy in oocytes. Concordance between aCGH and NGS was obtained for both PBs for
{"title":"Aneuploidy in Oocytes From Women of Advanced Maternal Age: Analysis of the Causal Meiotic Errors and Impact on Embryo Development","authors":"P. Verdyck, G. Altarescu, S. Santos-Ribeiro, C. Vrettou, U. Koehler, G. Griesinger, V. Goossens, C. Magli, C. Albanese, M. Parriego, L. Coll, R. Ron-El, K. Sermon, J. Traeger-Synodinos","doi":"10.1097/ogx.0000000000001254","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001254","url":null,"abstract":"\u0000 Many chromosome abnormalities are commonly observed and can lead to early pregnancy loss, miscarriage, or the birth of children with chromosomal defects. Such abnormalities are considered a major factor in the low pregnancy rate after assisted reproductive technology and natural conception. Preimplantation genetic testing for aneuploidy (PGT-A) aims to minimize the transfer of aneuploid embryos. Embryonic aneuploidies arising from errors in meiosis have an incidence of approximately 25% in embryos from women younger than 35 years, to more than half in embryos from women aged older than 35 years. Although these embryos are able to develop to the blastocyst stage, they tend to be of lower morphological quality. A recent multicenter randomized clinical trial (ESTEEM) analyzed polar bodies (PBs) from women after intracytoplasmic sperm injection aged between 36 and 40 years using microarrays in 205 cycles and found that the transfer of embryos from euploid oocytes did not lead to a higher live birth rate but was associated with a reduction in the number of embryo transfers and miscarriages.\u0000 This study aimed to evaluate all PB results from this RCT and characterize the types of chromosomal abnormalities and the chromosomes most frequently affected. The ESTEEM trial obtained biopsy of first (PB1) and second (PB2) PB in the cohort receiving PGT-A and analyzed them using array comparative genomic hybridization (aCGH). A total of 693 PB pairs had full results available, including 676 confirmed fertilized oocytes. Chromosome segregations, including likely underlying mechanisms, from these pairs are reported here. To estimate the reliability of the aCGH procedure, 72 PB pairs from a single center were reanalyzed using next-generation sequencing (NGS). Embryos were classified into 4 categories based on morphology: good, fair, poor, and degenerated. A comparative analysis was performed to assess the association between chromosome status and embryo quality as well as study group (PGT-A vs control) and embryo quality.\u0000 A total of 213/676 oocytes were euploid and 413/676 were aneuploid, whereas in the remaining 50 oocytes, an abnormality observed in PB1 was compensated by an abnormality in PB2. A total of 693 PB pairs reported chromatic numbers with results for 15,939 chromosomes. An abnormal segregation, in PB1 and/or PB2, was observed in 1162 chromosomes (7.3%) in 461 PB pairs. Chromosomes 22 (16.7%), 16 (16.6%), 19 (14.4%), 21 (13.7%), and 15 (12.4%) had the highest frequencies for abnormal segregations. The abnormal segregations were compatible with precocious separation of sister chromatids in meiosis 1 (M1) (n = 568; 48.9%), nondisjunction of chromatics in meiosis 2 (M2) or reverse segregation (n = 417; 35.9%), and nondisjunction in M1 (n = 65; 5.6%). However, 112 chromosomes had segregation patterns that could not be categorized into 1 of the 9 known mechanisms causing aneuploidy in oocytes. Concordance between aCGH and NGS was obtained for both PBs for","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"60 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272917","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 : 2024-03-01DOI: 10.1097/01.ogx.0001010432.99677.5a
F. Bretelle, Sandrine Loubière, R. Desbriere, A. Loundou, Julie Blanc, Hélène Heckenroth, Thomas Schmitz, A. Benachi, B. Haddad, F. Mauviel, X. Danoy, Pierre Mares, N. Chenni, J. Menard, Jean-François Cocallemen, Nadia Slim, M. Sénat, C. Chauleur, C. Bohec, G. Kayem, C. Trastour, A. Bongain, P. Rozenberg, Valerie Serazin, Florence Fenollar
One of the risk factors for preterm birth (PTB) is bacterial vaginosis (BV), a common, often asymptomatic, vaginal dysbiosis. The earlier BV is diagnosed based on gestational age, the higher the risk of PTB. The effectiveness of a screen-and-treat strategy for BV during pregnancy remains a source of debate. One meta-analyses, including 5 studies and 2346 patients, showed a benefit to screen and treat using clindamycin. Another, with 21 studies and 7847 patients, did not recommend BV screening but observed reductions in preterm delivery by 50% and miscarriages by 80%. In another systematic review, with 48 studies, there was varying accuracy across conventional screening tests for BV and suggested no or inconclusive efficacy in the treatment of asymptomatic BV in the general obstetric population and in those with a history of preterm delivery. Based on these studies, French and international organizations recommend against screening for BV with conventional diagnosis tools in low-risk populations. However, molecular diagnostic tools have been shown to be more accurate in identifying vaginal microbiota than conventional tools, such as clinical diagnosis based on Amsel or Nugent criteria. Molecular tools have been shown to provide an objective, reproducible, quantitative diagnosis of BV, identifying emergent pathogen species, such as Atopobium vaginae (now known as Fannyhessea vaginae). To date, no randomized studies have been conducted to assess the impact of molecular tools on a screen-and-treat intervention to BV. The aim of this study was to assess whether a screen-and-treat intervention using a molecular diagnostic tool is cost-effective in reducing the rate of PTB. The AuTop Trial was a prospective, open-label superiority trial conducted in 19 French maternity hospitals from March 9, 2015, to December 18, 2017. Included were adult women in early pregnancy (<20 weeks of gestation), with no history of PTB or late abortion and no major risk factors for prematurity. Excluded were patients who had extrauterine pregnancy or nonprogressive pregnancy, or were treated with antibiotics a week before inclusion in the study. Women were randomly assigned 1:1 to undergo molecular screening and treatment (intervention group) or receive usual care (control group). The intervention group was asked to self-collect vaginal swabs and return them within 15 days of collection for each month until 28 weeks of gestation. If BV was detected, treatment with azithromycin (1 g repeated after 48 hours) or amoxicillin (2 g/d for 7 days) was provided within 48 hours. A molecular biology-based rapid diagnostic tool designed for point-of-care testing was developed using real-time polymerase chain reaction assays to quantify DNA levels of A. vaginae. The tool's specificity, sensitivity, positive predictive value, and negative predicative value of the tool were 99%, 95%, 95%, and 99%, respectively, compared with other diagnostic techniques. The control group received usual ca
{"title":"Effectiveness and Costs of Molecular Screening and Treatment for Bacterial Vaginosis to Prevent Preterm Birth: The AuTop Randomized Clinical Trial","authors":"F. Bretelle, Sandrine Loubière, R. Desbriere, A. Loundou, Julie Blanc, Hélène Heckenroth, Thomas Schmitz, A. Benachi, B. Haddad, F. Mauviel, X. Danoy, Pierre Mares, N. Chenni, J. Menard, Jean-François Cocallemen, Nadia Slim, M. Sénat, C. Chauleur, C. Bohec, G. Kayem, C. Trastour, A. Bongain, P. Rozenberg, Valerie Serazin, Florence Fenollar","doi":"10.1097/01.ogx.0001010432.99677.5a","DOIUrl":"https://doi.org/10.1097/01.ogx.0001010432.99677.5a","url":null,"abstract":"\u0000 One of the risk factors for preterm birth (PTB) is bacterial vaginosis (BV), a common, often asymptomatic, vaginal dysbiosis. The earlier BV is diagnosed based on gestational age, the higher the risk of PTB. The effectiveness of a screen-and-treat strategy for BV during pregnancy remains a source of debate. One meta-analyses, including 5 studies and 2346 patients, showed a benefit to screen and treat using clindamycin. Another, with 21 studies and 7847 patients, did not recommend BV screening but observed reductions in preterm delivery by 50% and miscarriages by 80%. In another systematic review, with 48 studies, there was varying accuracy across conventional screening tests for BV and suggested no or inconclusive efficacy in the treatment of asymptomatic BV in the general obstetric population and in those with a history of preterm delivery. Based on these studies, French and international organizations recommend against screening for BV with conventional diagnosis tools in low-risk populations. However, molecular diagnostic tools have been shown to be more accurate in identifying vaginal microbiota than conventional tools, such as clinical diagnosis based on Amsel or Nugent criteria. Molecular tools have been shown to provide an objective, reproducible, quantitative diagnosis of BV, identifying emergent pathogen species, such as Atopobium vaginae (now known as Fannyhessea vaginae). To date, no randomized studies have been conducted to assess the impact of molecular tools on a screen-and-treat intervention to BV. The aim of this study was to assess whether a screen-and-treat intervention using a molecular diagnostic tool is cost-effective in reducing the rate of PTB.\u0000 The AuTop Trial was a prospective, open-label superiority trial conducted in 19 French maternity hospitals from March 9, 2015, to December 18, 2017. Included were adult women in early pregnancy (<20 weeks of gestation), with no history of PTB or late abortion and no major risk factors for prematurity. Excluded were patients who had extrauterine pregnancy or nonprogressive pregnancy, or were treated with antibiotics a week before inclusion in the study. Women were randomly assigned 1:1 to undergo molecular screening and treatment (intervention group) or receive usual care (control group). The intervention group was asked to self-collect vaginal swabs and return them within 15 days of collection for each month until 28 weeks of gestation. If BV was detected, treatment with azithromycin (1 g repeated after 48 hours) or amoxicillin (2 g/d for 7 days) was provided within 48 hours. A molecular biology-based rapid diagnostic tool designed for point-of-care testing was developed using real-time polymerase chain reaction assays to quantify DNA levels of A. vaginae. The tool's specificity, sensitivity, positive predictive value, and negative predicative value of the tool were 99%, 95%, 95%, and 99%, respectively, compared with other diagnostic techniques. The control group received usual ca","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"59 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273102","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 : 2024-03-01DOI: 10.1097/01.ogx.0001010428.64638.5b
Mary E. Norton, Cora Macpherson, Zach Demko, M. Egbert, F.D. Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, R. Faro, R. Madankumar, N. Strong, Sina Haeri, Robert Silver, Nidhi Vohra, Jonathan A. Hyett, K. Martin, M. Rabinowitz, Bo Jacobsson, Pe'er Dar
Although cell-free DNA (cfDNA) prenatal screening is widely used and has high sensitivity and specificity, there are circumstances in which the screening does not provide an interpretable result. Although this is relatively uncommon, it happens enough that clinical implications and potential reasons for follow-up should be studied and assessed. This study was designed to evaluate outcomes for pregnancies with nonreportable results on cfDNA screening tests. This study was a secondary analysis of the data from a multicenter prospective observational study of cfDNA screening for aneuploidy and 22q11.2 deletion syndrome. All patients were tested for trisomies 13, 18, and 21, as well as the 22q11.2 deletion syndrome, and all patients had confirmatory testing on the newborns in addition to collecting obstetric and perinatal outcomes. Inclusion criteria were women older than 18 years and at greater than 9 weeks of gestation with a singleton pregnancy. Exclusion criteria were having received cfDNA screening results before enrollment, organ transplant, ovum donation, vanishing twin, or being unwilling to provide a newborn sample. The primary outcome was the rate of adverse obstetrical and perinatal outcomes, including aneuploidy; preterm birth at less than 28, 34, or 37 weeks' gestation; preeclampsia; small for gestational age birth; and a composite outcome that included preterm birth before 37 weeks, preeclampsia, stillbirth at greater than 20 weeks, and small for gestational age. Final analyses included 17,851 individuals who had cfDNA screening, confirmatory genetic testing on the newborn, and obstetrical and perinatal outcomes recorded. Nonreportable results were found in 602 individuals (3.4%) after the first draw, with 32.2% of these due to low fetal fraction. Another third of the cohort had patterns where the risk of aneuploidy was uninterpretable but with an adequate fetal fraction, and in the final third, the fetal fraction could not be measured. Of the original 602 cases of nonreportable findings, 427 had a second draw, with 112 of these (26.2%) again having nonreportable results. There were no significant differences in baseline characteristics of age and parity for those with successful versus nonreportable test results; gestational age was significantly higher in individuals with nonreportable results (14.4 vs 13.4 weeks, P < 0.001), as was body mass index (26.2 vs 31.3), and the rate of chronic hypertension (4.0% vs 9.7%). In this cohort, there were 133 genetically confirmed trisomies, with 100 fetuses with trisomy 21, 18 individuals with trisomy 18, and 15 individuals with trisomy 13. Overall, the rate of aneuploidy was 1.7% in individuals with nonreportable results, versus 0.7% in those with reported results (P = 0.013; adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.1–4.0). Rates of preterm birth were also higher in those with nonreportable test results, with delivery at less than 34 weeks at 1.5% in those with a test
{"title":"Obstetrical, Perinatal, and Genetic Outcomes Associated With Nonreportable Prenatal Cell-Free DNA Screening Results","authors":"Mary E. Norton, Cora Macpherson, Zach Demko, M. Egbert, F.D. Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, R. Faro, R. Madankumar, N. Strong, Sina Haeri, Robert Silver, Nidhi Vohra, Jonathan A. Hyett, K. Martin, M. Rabinowitz, Bo Jacobsson, Pe'er Dar","doi":"10.1097/01.ogx.0001010428.64638.5b","DOIUrl":"https://doi.org/10.1097/01.ogx.0001010428.64638.5b","url":null,"abstract":"\u0000 Although cell-free DNA (cfDNA) prenatal screening is widely used and has high sensitivity and specificity, there are circumstances in which the screening does not provide an interpretable result. Although this is relatively uncommon, it happens enough that clinical implications and potential reasons for follow-up should be studied and assessed. This study was designed to evaluate outcomes for pregnancies with nonreportable results on cfDNA screening tests.\u0000 This study was a secondary analysis of the data from a multicenter prospective observational study of cfDNA screening for aneuploidy and 22q11.2 deletion syndrome. All patients were tested for trisomies 13, 18, and 21, as well as the 22q11.2 deletion syndrome, and all patients had confirmatory testing on the newborns in addition to collecting obstetric and perinatal outcomes. Inclusion criteria were women older than 18 years and at greater than 9 weeks of gestation with a singleton pregnancy. Exclusion criteria were having received cfDNA screening results before enrollment, organ transplant, ovum donation, vanishing twin, or being unwilling to provide a newborn sample. The primary outcome was the rate of adverse obstetrical and perinatal outcomes, including aneuploidy; preterm birth at less than 28, 34, or 37 weeks' gestation; preeclampsia; small for gestational age birth; and a composite outcome that included preterm birth before 37 weeks, preeclampsia, stillbirth at greater than 20 weeks, and small for gestational age.\u0000 Final analyses included 17,851 individuals who had cfDNA screening, confirmatory genetic testing on the newborn, and obstetrical and perinatal outcomes recorded. Nonreportable results were found in 602 individuals (3.4%) after the first draw, with 32.2% of these due to low fetal fraction. Another third of the cohort had patterns where the risk of aneuploidy was uninterpretable but with an adequate fetal fraction, and in the final third, the fetal fraction could not be measured. Of the original 602 cases of nonreportable findings, 427 had a second draw, with 112 of these (26.2%) again having nonreportable results. There were no significant differences in baseline characteristics of age and parity for those with successful versus nonreportable test results; gestational age was significantly higher in individuals with nonreportable results (14.4 vs 13.4 weeks, P < 0.001), as was body mass index (26.2 vs 31.3), and the rate of chronic hypertension (4.0% vs 9.7%).\u0000 In this cohort, there were 133 genetically confirmed trisomies, with 100 fetuses with trisomy 21, 18 individuals with trisomy 18, and 15 individuals with trisomy 13. Overall, the rate of aneuploidy was 1.7% in individuals with nonreportable results, versus 0.7% in those with reported results (P = 0.013; adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.1–4.0). Rates of preterm birth were also higher in those with nonreportable test results, with delivery at less than 34 weeks at 1.5% in those with a test ","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"250 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140274241","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 : 2024-02-01DOI: 10.1097/01.ogx.0001008536.08634.9f
S. L. Aronson, Marta Lopez-Yurda, S. Koole, J. H. Schagen van Leeuwen, H. W. Schreuder, R. Hermans, I. D. de Hingh, Mignon D.J.M. van Gent, H. Arts, M. van Ham, Peter A. van Dam, Peter Vuylsteke, A. Aalbers, V. Verwaal, K. K. Van de Vijver, Neil K. Aaronson, G. Sonke, W. V. van Driel
(Abstracted from Lancet Oncol 2023;24:P1109–P1118) Although the 5-year survival of patients with advanced ovarian cancer has improved, overall survival at 10 years remains approximately 13%. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the delivery of chemotherapeutic agents directly into the peritoneum in combination with hyperthermia, which enhances penetration and increases sensitivity to platinum compounds by inducing a transient state of homologous recombination deficiency.
{"title":"Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer (OVHIPEC-1): Final Survival Analysis of a Randomised, Controlled, Phase 3 Trial","authors":"S. L. Aronson, Marta Lopez-Yurda, S. Koole, J. H. Schagen van Leeuwen, H. W. Schreuder, R. Hermans, I. D. de Hingh, Mignon D.J.M. van Gent, H. Arts, M. van Ham, Peter A. van Dam, Peter Vuylsteke, A. Aalbers, V. Verwaal, K. K. Van de Vijver, Neil K. Aaronson, G. Sonke, W. V. van Driel","doi":"10.1097/01.ogx.0001008536.08634.9f","DOIUrl":"https://doi.org/10.1097/01.ogx.0001008536.08634.9f","url":null,"abstract":"(Abstracted from Lancet Oncol 2023;24:P1109–P1118)\u0000 Although the 5-year survival of patients with advanced ovarian cancer has improved, overall survival at 10 years remains approximately 13%. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the delivery of chemotherapeutic agents directly into the peritoneum in combination with hyperthermia, which enhances penetration and increases sensitivity to platinum compounds by inducing a transient state of homologous recombination deficiency.","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139966027","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 : 2024-01-01DOI: 10.1097/01.ogx.0001006904.38530.bf
Matthew K. Hoffman, R. Clifton, J. Biggio, G. Saade, Lynda G. Ugwu, Monica Longo, S. Bousleiman, K. Clark, William A. Grobman, Heather A. Frey, Suneet P. Chauhan, Lorraine Dugoff, Tracy A. Manuck, Edward K. Chien, D. J. Rouse, H. Simhan, M. Esplin, G. Macones
(Abstracted from JAMA 2023;330(4):340–348) Preterm delivery remains a public health issue, affecting many pregnant patients and their infants each year. There are a number of causes and associations with preterm delivery, with some that are identifiable and treatable and some that are not; one association that has been well established is the connection between preterm birth (PTB) and a short cervix.
{"title":"Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial","authors":"Matthew K. Hoffman, R. Clifton, J. Biggio, G. Saade, Lynda G. Ugwu, Monica Longo, S. Bousleiman, K. Clark, William A. Grobman, Heather A. Frey, Suneet P. Chauhan, Lorraine Dugoff, Tracy A. Manuck, Edward K. Chien, D. J. Rouse, H. Simhan, M. Esplin, G. Macones","doi":"10.1097/01.ogx.0001006904.38530.bf","DOIUrl":"https://doi.org/10.1097/01.ogx.0001006904.38530.bf","url":null,"abstract":"(Abstracted from JAMA 2023;330(4):340–348)\u0000 Preterm delivery remains a public health issue, affecting many pregnant patients and their infants each year. There are a number of causes and associations with preterm delivery, with some that are identifiable and treatable and some that are not; one association that has been well established is the connection between preterm birth (PTB) and a short cervix.","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"47 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139635526","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 : 2024-01-01DOI: 10.1097/01.ogx.0001006896.53429.28
Natalie A. Cameron, Lynn M. Yee, B. Dolan, Matthew J. O’Brien, Philip Greenland, Sadiya S. Khan
(Abstracted from JAMA 2023;330(4):359–367) Cardiovascular (CV) disease is one of the leading causes of death in the United States. In particular, it has been increasing in its contribution to the deaths of women; one area of care that is critical but sometimes overlooked is CV health postpartum.
{"title":"Trends in Cardiovascular Health Counseling Among Postpartum Individuals","authors":"Natalie A. Cameron, Lynn M. Yee, B. Dolan, Matthew J. O’Brien, Philip Greenland, Sadiya S. Khan","doi":"10.1097/01.ogx.0001006896.53429.28","DOIUrl":"https://doi.org/10.1097/01.ogx.0001006896.53429.28","url":null,"abstract":"(Abstracted from JAMA 2023;330(4):359–367)\u0000 Cardiovascular (CV) disease is one of the leading causes of death in the United States. In particular, it has been increasing in its contribution to the deaths of women; one area of care that is critical but sometimes overlooked is CV health postpartum.","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139639209","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 : 2024-01-01DOI: 10.1097/ogx.0000000000001222
Vera Kelesidou, I. Tsakiridis, Andriana Virgiliou, T. Dagklis, A. Mamopoulos, A. Athanasiadis, I. Kalogiannidis
Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and misoprostol; however, different doses and routes of administration have been proposed. The aim of this study was to summarize published data on the effectiveness, adverse effects, and acceptability of the various combinations of mifepristone and misoprostol in medical abortion protocols in the first trimester of pregnancy. This was a comprehensive review, synthesizing the findings of the literature on the current use of mifepristone and misoprostol for first-trimester abortion. The combination of mifepristone and misoprostol seems to be more effective than misoprostol alone. Regarding the dosages and routes, mifepristone is administered orally, and the optimal dose is 200 mg. The route of administration of misoprostol varies; the sublingual and buccal routes are more effective; however, the vaginal route (800 μg) is associated with fewer adverse effects. Finally, the acceptability rates did not differ significantly. Different schemes for first-trimester medical abortion have been described so far. Future research needs to focus on identifying the method that offers the best trade-off between efficacy and safety in first-trimester medical abortion. Obstetricians and gynecologists, family physicians After participating in this activity, the learner should be better able to discuss available combinations of mifepristone and misoprostol for first-trimester medical abortion; describe the recommended doses of misoprostol for first-trimester medical abortion; and assess the adverse effects caused by misoprostol when administered by different routes.
{"title":"Combination of Mifepristone and Misoprostol for First-Trimester Medical Abortion: A Comprehensive Review of the Literature","authors":"Vera Kelesidou, I. Tsakiridis, Andriana Virgiliou, T. Dagklis, A. Mamopoulos, A. Athanasiadis, I. Kalogiannidis","doi":"10.1097/ogx.0000000000001222","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001222","url":null,"abstract":"\u0000 \u0000 \u0000 Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and misoprostol; however, different doses and routes of administration have been proposed.\u0000 \u0000 \u0000 \u0000 The aim of this study was to summarize published data on the effectiveness, adverse effects, and acceptability of the various combinations of mifepristone and misoprostol in medical abortion protocols in the first trimester of pregnancy.\u0000 \u0000 \u0000 \u0000 This was a comprehensive review, synthesizing the findings of the literature on the current use of mifepristone and misoprostol for first-trimester abortion.\u0000 \u0000 \u0000 \u0000 The combination of mifepristone and misoprostol seems to be more effective than misoprostol alone. Regarding the dosages and routes, mifepristone is administered orally, and the optimal dose is 200 mg. The route of administration of misoprostol varies; the sublingual and buccal routes are more effective; however, the vaginal route (800 μg) is associated with fewer adverse effects. Finally, the acceptability rates did not differ significantly.\u0000 \u0000 \u0000 \u0000 Different schemes for first-trimester medical abortion have been described so far. Future research needs to focus on identifying the method that offers the best trade-off between efficacy and safety in first-trimester medical abortion.\u0000 \u0000 \u0000 \u0000 Obstetricians and gynecologists, family physicians\u0000 \u0000 \u0000 \u0000 After participating in this activity, the learner should be better able to discuss available combinations of mifepristone and misoprostol for first-trimester medical abortion; describe the recommended doses of misoprostol for first-trimester medical abortion; and assess the adverse effects caused by misoprostol when administered by different routes.\u0000","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"120 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139639422","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 : 2024-01-01DOI: 10.1097/ogx.0000000000001225
Linda M. Zambrano Guevara, Caledonia Buckheit, J. Kuller, Beverly Gray, Sarah K. Dotters-Katz
Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric practice. However, techniques around labor and induction management vary widely. Evidence-based practice regarding induction and labor management can reduce birth complications such as infection and hemorrhage and decrease rates of cesarean delivery. To review existing evidence on IOL and labor management strategies with respect to preparing for induction, cervical ripening, induction and augmentation, and second stage of labor techniques. Review of recent original research, review articles, and guidelines on IOL using PubMed (2000–2022). Preinduction, pelvic floor training and perineal massage reduce postpartum urinary incontinence and perineal trauma, respectively. Timely membrane sweeping (38 weeks) can promote spontaneous labor and prevent postterm inductions. Outpatient Foley bulb placement in low-risk nulliparous patients with planned IOL reduces time to delivery. Inpatient Foley bulb use beyond 6 to 12 hours shows no benefit. When synthetic prostaglandins are indicated, vaginal misoprostol should be preferred. For nulliparous patients and those with obesity, oxytocin should be titrated using a high-dose protocol. Once cervical dilation is complete, pushing should begin immediately. Warm compresses and perineal massage decrease risk of perineal trauma. Several strategies exist to assist in successful IOL and promote vaginal delivery. Evidence-based strategies should be used to improve outcomes and decrease risk of complications and cesarean delivery. Recommendations should be shared across interdisciplinary team members, creating a model that promotes safe patient care. Obstetricians and gynecologists, family physicians Discuss the current evidence and best practices regarding prelabor interventions to improve delivery outcomes; describe evidence-based methods of cervical ripening; outline data-driven practices to progress induction; and explain methods to improve birth outcomes and reduce risks in the second stage of labor.
{"title":"Evidence Based Management of Labor","authors":"Linda M. Zambrano Guevara, Caledonia Buckheit, J. Kuller, Beverly Gray, Sarah K. Dotters-Katz","doi":"10.1097/ogx.0000000000001225","DOIUrl":"https://doi.org/10.1097/ogx.0000000000001225","url":null,"abstract":"\u0000 \u0000 \u0000 Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric practice. However, techniques around labor and induction management vary widely. Evidence-based practice regarding induction and labor management can reduce birth complications such as infection and hemorrhage and decrease rates of cesarean delivery.\u0000 \u0000 \u0000 \u0000 To review existing evidence on IOL and labor management strategies with respect to preparing for induction, cervical ripening, induction and augmentation, and second stage of labor techniques.\u0000 \u0000 \u0000 \u0000 Review of recent original research, review articles, and guidelines on IOL using PubMed (2000–2022).\u0000 \u0000 \u0000 \u0000 Preinduction, pelvic floor training and perineal massage reduce postpartum urinary incontinence and perineal trauma, respectively. Timely membrane sweeping (38 weeks) can promote spontaneous labor and prevent postterm inductions. Outpatient Foley bulb placement in low-risk nulliparous patients with planned IOL reduces time to delivery. Inpatient Foley bulb use beyond 6 to 12 hours shows no benefit. When synthetic prostaglandins are indicated, vaginal misoprostol should be preferred. For nulliparous patients and those with obesity, oxytocin should be titrated using a high-dose protocol. Once cervical dilation is complete, pushing should begin immediately. Warm compresses and perineal massage decrease risk of perineal trauma.\u0000 \u0000 \u0000 \u0000 Several strategies exist to assist in successful IOL and promote vaginal delivery. Evidence-based strategies should be used to improve outcomes and decrease risk of complications and cesarean delivery. Recommendations should be shared across interdisciplinary team members, creating a model that promotes safe patient care.\u0000 \u0000 \u0000 \u0000 Obstetricians and gynecologists, family physicians\u0000 \u0000 \u0000 \u0000 Discuss the current evidence and best practices regarding prelabor interventions to improve delivery outcomes; describe evidence-based methods of cervical ripening; outline data-driven practices to progress induction; and explain methods to improve birth outcomes and reduce risks in the second stage of labor.\u0000","PeriodicalId":509854,"journal":{"name":"Obstetrical & Gynecological Survey","volume":"11 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139633214","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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