Immune thrombocytopenic purpura (ITP) affects 1–3 out of every 10 000 pregnancies, posing significant risks to both mothers and newborns. The condition often requires careful management to prevent severe hemorrhagic events. PubMed, Embase, Scopus, and Web of Science searched for relevant literature until June 2024. A meta-analysis was performed to evaluate the effect of ITP on maternal and fetal outcomes. The results showed that antepartum hemorrhage occurred in 0.17 (95% CI = 0.12–0.25) of patients and postpartum hemorrhage occurred in 0.11 (95% CI = 0.07–0.16) of pregnant women with ITP. About 0.63 (95% CI = 0.50–0.74) of pregnant women needed treatment for ITP. The cesarean section (CS) rate was 0.48 (95% CI = 0.34–0.61), and the occurrence of preterm labor was 0.14 (95% CI = 0.07–0.24). A total of 0.32 of neonates had thrombocytopenia (95% CI = 0.18–0.52). The difference between the platelet count of those diagnosed with ITP before pregnancy and those diagnosed after pregnancy was significant (MD = –31.50, 95% CI = 51.29–11.72, p < 0.01). This meta-analysis highlights the significant impact of ITP on pregnancy, estimating risks of bleeding, CS, gestational diabetes, preterm labor, and neonatal thrombocytopenia. These findings underscore the need for vigilant monitoring and tailored management of pregnant women with ITP.
免疫性血小板减少性紫癜（ITP）每 10 000 名孕妇中就有 1-3 人患病，对母亲和新生儿都有很大风险。这种疾病通常需要精心治疗，以防止严重出血事件的发生。PubMed、Embase、Scopus和Web of Science检索了截至2024年6月的相关文献。我们进行了一项荟萃分析，以评估 ITP 对产妇和胎儿预后的影响。结果显示，在ITP孕妇中，0.17（95% CI = 0.12-0.25）的患者会发生产前出血，0.11（95% CI = 0.07-0.16）的患者会发生产后出血。约有 0.63（95% CI = 0.50-0.74）名孕妇需要治疗 ITP。剖宫产率为 0.48（95% CI = 0.34-0.61），早产率为 0.14（95% CI = 0.07-0.24）。共有 0.32 名新生儿患有血小板减少症（95% CI = 0.18-0.52）。孕前诊断为 ITP 的新生儿和孕后诊断为 ITP 的新生儿的血小板计数差异显著（MD = -31.50，95% CI = 51.29-11.72，p＜0.05）。
{"title":"Immune Thrombocytopenic Purpura and Maternal and Neonatal Outcomes During Pregnancy: A Systematic Review and Meta-Analysis","authors":"Hong Zhang, Lixia Shi, Hui Shang, Huili Yang","doi":"10.1111/aji.70008","DOIUrl":"10.1111/aji.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune thrombocytopenic purpura (ITP) affects 1–3 out of every 10 000 pregnancies, posing significant risks to both mothers and newborns. The condition often requires careful management to prevent severe hemorrhagic events. PubMed, Embase, Scopus, and Web of Science searched for relevant literature until June 2024. A meta-analysis was performed to evaluate the effect of ITP on maternal and fetal outcomes. The results showed that antepartum hemorrhage occurred in 0.17 (95% CI = 0.12–0.25) of patients and postpartum hemorrhage occurred in 0.11 (95% CI = 0.07–0.16) of pregnant women with ITP. About 0.63 (95% CI = 0.50–0.74) of pregnant women needed treatment for ITP. The cesarean section (CS) rate was 0.48 (95% CI = 0.34–0.61), and the occurrence of preterm labor was 0.14 (95% CI = 0.07–0.24). A total of 0.32 of neonates had thrombocytopenia (95% CI = 0.18–0.52). The difference between the platelet count of those diagnosed with ITP before pregnancy and those diagnosed after pregnancy was significant (MD = –31.50, 95% CI = 51.29–11.72, <i>p</i> < 0.01). This meta-analysis highlights the significant impact of ITP on pregnancy, estimating risks of bleeding, CS, gestational diabetes, preterm labor, and neonatal thrombocytopenia. These findings underscore the need for vigilant monitoring and tailored management of pregnant women with ITP.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keren Zloto, Shani Steinberg, Shir Lev, Rakefet Yoeli-Ullman, Stanley Niznik, Nancy Agmon-Levin, Keren Ofir
Objective
In recent years antiphospholipid syndrome (APS) as well as antiphospholipid antibodies (aPL) prevalence has demonstrated an upward trend in women during reproductive age. There is a lack of data concerning its effects on women with grand multiparity (GMP) (parity ≥5). Hence, this study aimed to assess pregnancy outcomes among GMP aPL/APS patients.
Study Design
We retrospectively assembled the births of GMP women with aPL/APS, between 2017 and 2022 in the Sheba Medical Center. We compared their deliveries with those of two control groups: (1) the “aPL/APS-controls”—of pregnant women with aPL/APS and parity <5. (2) The “GMP-controls”- parity ≥5 without aPL/APS. We examined demographics, aPL characteristics, pregnancy, and neonatal outcomes between the groups.
Results
In total, 42 deliveries in the study group were compared to 461 deliveries in the “aPL/APS-controls” group and 84 deliveries of the “GMP-controls.” Most parameters were similar across groups. However, the study group had a higher rate of obstetric APS diagnosis (64.64% vs. 83.33%, p < 0.01) and showed significant differences such as older maternal age, higher BMI, more polyhydramnios cases, and larger babies compared to controls (33.91 vs. 36.19, p = 0.05; 23.2 vs. 28.89, p = 0.02; 3.68 vs. 11.9, p = 0.01; and 2.17 vs. 14.28, p < 0.01, respectively).
Conclusions
Our findings reveal that perinatal outcomes in aPL/APS GMP women are comparable and not inferior to those in aPL/APS women with <5 pregnancies or in comparison to the general GMP population. The minor differences observed may all be related to GMP women's older age and higher BMI.
{"title":"Pregnancy Outcomes in Grand Multiparity Women With Antiphospholipid Antibodies","authors":"Keren Zloto, Shani Steinberg, Shir Lev, Rakefet Yoeli-Ullman, Stanley Niznik, Nancy Agmon-Levin, Keren Ofir","doi":"10.1111/aji.70013","DOIUrl":"10.1111/aji.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In recent years antiphospholipid syndrome (APS) as well as antiphospholipid antibodies (aPL) prevalence has demonstrated an upward trend in women during reproductive age. There is a lack of data concerning its effects on women with grand multiparity (GMP) (parity ≥5). Hence, this study aimed to assess pregnancy outcomes among GMP aPL/APS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design</h3>\u0000 \u0000 <p>We retrospectively assembled the births of GMP women with aPL/APS, between 2017 and 2022 in the Sheba Medical Center. We compared their deliveries with those of two control groups: (1) the “aPL/APS-controls”—of pregnant women with aPL/APS and parity <5. (2) The “GMP-controls”- parity ≥5 without aPL/APS. We examined demographics, aPL characteristics, pregnancy, and neonatal outcomes between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 42 deliveries in the study group were compared to 461 deliveries in the “aPL/APS-controls” group and 84 deliveries of the “GMP-controls.” Most parameters were similar across groups. However, the study group had a higher rate of obstetric APS diagnosis (64.64% vs. 83.33%, <i>p</i> < 0.01) and showed significant differences such as older maternal age, higher BMI, more polyhydramnios cases, and larger babies compared to controls (33.91 vs. 36.19, <i>p</i> = 0.05; 23.2 vs. 28.89, <i>p</i> = 0.02; 3.68 vs. 11.9, <i>p</i> = 0.01; and 2.17 vs. 14.28, <i>p</i> < 0.01, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings reveal that perinatal outcomes in aPL/APS GMP women are comparable and not inferior to those in aPL/APS women with <5 pregnancies or in comparison to the general GMP population. The minor differences observed may all be related to GMP women's older age and higher BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fouzia Zahid Ali Khan, Saifuddin Ahmed, Anna Maya Powell
There are sparse data on the role of the vaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association with spontaneous preterm birth (sPTB). We conducted a scoping review to assess associations between vaginal microbiota and sPTB among PWLWH. Three studies were included, representing a total of 180 PWLWH out of 652 total pregnancies. All studies used modern DNA sequencing methods (16S rRNA amplification, metagenomics, or metatranscriptomics). PWLWH had higher VMB richness and diversity compared to HIV-uninfected pregnant women and higher sPTB rates in two of three studies. A higher proportion of sPTB among PWLWH was observed in those with Lactobacillus-deficient, anaerobe-dominant vaginal microbiota. In two of three studies, higher concentrations of vaginal inflammation markers were associated with increased VMB richness and diversity. HIV status was independently associated with sPTB. It is unclear if increased vaginal microbial diversity among PWLWH or increased vaginal inflammation contributes more to PTB, but HIV does appear to alter the VMB in pregnant individuals and may also affect PTB rates in microbiome-independent pathways. Given the limited number of studies, heterogeneity in sample size, sample collection methods, and inconsistent results it is difficult to causally link HIV, VMB, inflammatory cytokines, and sPTB.
{"title":"Vaginal Microbiome and the Risk of Preterm Birth in Women Living With HIV: A Scoping Review","authors":"Fouzia Zahid Ali Khan, Saifuddin Ahmed, Anna Maya Powell","doi":"10.1111/aji.70011","DOIUrl":"10.1111/aji.70011","url":null,"abstract":"<div>\u0000 \u0000 <p>There are sparse data on the role of the vaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association with spontaneous preterm birth (sPTB). We conducted a scoping review to assess associations between vaginal microbiota and sPTB among PWLWH. Three studies were included, representing a total of 180 PWLWH out of 652 total pregnancies. All studies used modern DNA sequencing methods (16S rRNA amplification, metagenomics, or metatranscriptomics). PWLWH had higher VMB richness and diversity compared to HIV-uninfected pregnant women and higher sPTB rates in two of three studies. A higher proportion of sPTB among PWLWH was observed in those with Lactobacillus-deficient, anaerobe-dominant vaginal microbiota. In two of three studies, higher concentrations of vaginal inflammation markers were associated with increased VMB richness and diversity. HIV status was independently associated with sPTB. It is unclear if increased vaginal microbial diversity among PWLWH or increased vaginal inflammation contributes more to PTB, but HIV does appear to alter the VMB in pregnant individuals and may also affect PTB rates in microbiome-independent pathways. Given the limited number of studies, heterogeneity in sample size, sample collection methods, and inconsistent results it is difficult to causally link HIV, VMB, inflammatory cytokines, and sPTB.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emiko Yamane, Yukihiro Azuma, Mei Matsumoto, Eri Sato, Yoshiaki Ota, Tasuku Harada, Fuminori Taniguchi
Problem
What is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?
Method of Study
Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including interleukin (IL)-6, IL-8, cyclooxygenase (COX)-2, transient receptor potential vanilloid (TRPV)1, ESR1, and ESR2, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.
Results
SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not NESCs. SR also reduced IL-6, IL-8, COX-2, TRPV1, ESR1, and ESR2 mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only TRPV1 mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.
Conclusions
SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.
{"title":"SR-16234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain-Related Factor Expression by Inhibition of the Nuclear Factor-kappa B Pathway in Endometriotic Stromal Cells","authors":"Emiko Yamane, Yukihiro Azuma, Mei Matsumoto, Eri Sato, Yoshiaki Ota, Tasuku Harada, Fuminori Taniguchi","doi":"10.1111/aji.70010","DOIUrl":"10.1111/aji.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>What is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including <i>interleukin</i> (<i>IL</i>)<i>-6</i>, <i>IL-8</i>, <i>cyclooxygenase</i> (<i>COX</i>)<i>-2</i>, <i>transient receptor potential vanilloid</i> (<i>TRPV</i>)<i>1</i>, <i>ESR1</i>, and <i>ESR2</i>, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not NESCs. SR also reduced <i>IL-6</i>, <i>IL-8</i>, <i>COX-2</i>, <i>TRPV1</i>, <i>ESR1</i>, and <i>ESR2</i> mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only <i>TRPV1</i> mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To gain insight into the endometrial pathophysiology of unexplained repeated implantation failure (RIF), we examined the characteristics of genital tract microbiota and explored the correlation between the microbiota and endometrial receptivity.
Methods
Vaginal secretion (VS) and endometrial biopsy (EB) samples were collected from patients with RIF (RIF group, n = 32) and those with infertility who had achieved pregnancy during their initial embryo transfer cycle (control group, n = 18). 16S ribosomal RNA sequencing and quantitative PCR were performed to characterize the microbiota of the two groups. Spearman's correlation analysis was performed to determine the relationship between endometrial receptivity markers and endometrial microbiota.
Results
Endometrial microbiota exhibited distinct characteristics from vaginal microbiota, with a higher alpha-diversity. Alpha-diversity of the endometrial microbiota was higher in the RIF group than in the control group. Compared with the control group, the RIF group had a significant decrease in endometrial Lactobacillus abundance and an increase in Gardnerella and Acinetobacter abundances. The expression levels of endometrial receptivity markers, including homeobox A11, integrin αvβ3, leukemia inhibitor factor, matrix metalloproteinase-9, and vascular endothelial growth factor, were lower in the RIF group than in the control group. Moreover, the expression levels of these markers were correlated with endometrial Lactobacillus, Gardnerella, and Acinetobacter abundances.
Conclusion
RIF is characterized by endometrial microbiota dysbiosis and poor endometrial receptivity. Moreover, abnormal endometrial microbiota is associated with impaired endometrial receptivity, which may be a potential cause of unexplained RIF.
{"title":"Altered Endometrial Microbiota Profile Is Associated With Poor Endometrial Receptivity of Repeated Implantation Failure","authors":"Rongxue Zhang, Miaomiao Wang, Jixiang Zhong, Huiying Xue","doi":"10.1111/aji.70005","DOIUrl":"10.1111/aji.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To gain insight into the endometrial pathophysiology of unexplained repeated implantation failure (RIF), we examined the characteristics of genital tract microbiota and explored the correlation between the microbiota and endometrial receptivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Vaginal secretion (VS) and endometrial biopsy (EB) samples were collected from patients with RIF (RIF group, <i>n</i> = 32) and those with infertility who had achieved pregnancy during their initial embryo transfer cycle (control group, <i>n</i> = 18). 16S ribosomal RNA sequencing and quantitative PCR were performed to characterize the microbiota of the two groups. Spearman's correlation analysis was performed to determine the relationship between endometrial receptivity markers and endometrial microbiota.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Endometrial microbiota exhibited distinct characteristics from vaginal microbiota, with a higher alpha-diversity. Alpha-diversity of the endometrial microbiota was higher in the RIF group than in the control group. Compared with the control group, the RIF group had a significant decrease in endometrial <i>Lactobacillus</i> abundance and an increase in <i>Gardnerella</i> and <i>Acinetobacter</i> abundances. The expression levels of endometrial receptivity markers, including homeobox A11, integrin αvβ3, leukemia inhibitor factor, matrix metalloproteinase-9, and vascular endothelial growth factor, were lower in the RIF group than in the control group. Moreover, the expression levels of these markers were correlated with endometrial <i>Lactobacillus, Gardnerella</i>, and <i>Acinetobacter</i> abundances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RIF is characterized by endometrial microbiota dysbiosis and poor endometrial receptivity. Moreover, abnormal endometrial microbiota is associated with impaired endometrial receptivity, which may be a potential cause of unexplained RIF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal–fetal complications in patients with low-titer aPLs.</p> </section> <section> <h3> Methods</h3> <p>The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (<i>n</i> = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (<i>n</i> = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal–fetal complications were subsequently compared.</p> </section> <section> <h3> Results</h3> <p>The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (<i>p</i> < 0.05) and a higher ANA positivity rate (<i>p</i> < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (<i>p</i> < 0.05). Post treatment, the live bi
{"title":"Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies","authors":"Yuxin Chen, Wenchao Xu, Shuang Huang, Juanli Li, Ting Li, Jian Chen, Yu Lu, Jianyu Zhang","doi":"10.1111/aji.13940","DOIUrl":"10.1111/aji.13940","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal–fetal complications in patients with low-titer aPLs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (<i>n</i> = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (<i>n</i> = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal–fetal complications were subsequently compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (<i>p</i> < 0.05) and a higher ANA positivity rate (<i>p</i> < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (<i>p</i> < 0.05). Post treatment, the live bi","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13940","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development.
Methods
Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)-mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein–protein interactions (PPIs) of the modification-related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k-means.
Results
We identified modification-related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4-cell stage to the 8-cell stage might be the demarcation period for modification-related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent.
Conclusions
The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine-tuned regulatory effects during embryonic development.
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Marisa R. Imbroane, Felicia LeMoine, Kelly S. Gibson
Problem
Research has suggested a link between recurrent pregnancy loss (RPL) and cell-mediated immunity dysregulation. We aimed to determine if a history of RPL is associated with diagnosis of a cell-mediated autoimmune condition (AIC).
Method of Study
A retrospective cohort study was conducted using the TriNetX research network. The RPL group had ≥3 spontaneous or missed abortions. Controls had at least one pregnancy but no diagnosis of RPL. Propensity score matching was used for age, race, and ethnicity. Z-test and relative risk analysis investigated the relationship between RPL and subsequent AIC diagnoses.
Results
One hundred twenty-eight thousand three hundred seventy-six patients were included in each cohort. RPL was associated with an increased risk for an AIC composite (RR 1.60, 95% CI [1.51, 1.69]), Crohn's disease, Graves’ disease, Hashimoto's thyroiditis, multiple sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and ulcerative colitis, but not psoriatic arthritis.
Conclusions
Using a large research database of patients with RPL, we were able to demonstrate that an antecedent diagnosis of RPL is associated with increased risk of subsequent diagnosis of an AIC, often between 1 and 10 years after RPL.
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Madeleine M. Jordan, Emmanuel Amabebe, Kamil Khanipov, Brandie DePaoli Taylor
Limited studies have investigated the role of the microbiota in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, which often results in preterm birth. We evaluated 23 studies that explored the relationship between gut, vaginal, oral, or placental microbiotas and HDP. Scopus, ProQuest Health Research Premium Collection, ProQuest Nursing & Allied Health Database, EBSCO, and Ovid were searched for relevant literature. Majority (18) of studies focused on the gut microbiota, and far fewer examined the oral cavity (3), vagina (3), and placenta (1). One study examined the gut, oral, and vaginal microbiotas. The consensus highlights a potential role for microbiota dysbiosis in preeclampsia and HDP. Especially in the third trimester, preeclampsia is associated with gut dysbiosis—deficient in beneficial species of Akkermansia, Bifidobacterium, and Coprococcus but enriched with pathogenic Campylobacterota and Candidatus Saccharibacteria, with low community α-diversity. Similarly, the preeclamptic vaginal and oral microbiotas are enriched with bacterial vaginosis and periodontal disease-associated species, respectively. The trend is also observed in the placenta, which is colonized by gastrointestinal, respiratory tract, and periodontitis-related pathogens. Consequently, a chronic proinflammatory state that adversely impacts placentation is implicated. These observations however require more mechanistic studies to establish the timing of the preceding immune dysfunction and any causality.
关于微生物群在妊娠高血压疾病（HDP）中的作用，尤其是经常导致早产的先兆子痫中的作用的研究很有限。我们评估了 23 项探讨肠道、阴道、口腔或胎盘微生物群与 HDP 之间关系的研究。我们检索了 Scopus、ProQuest Health Research Premium Collection、ProQuest Nursing & Allied Health Database、EBSCO 和 Ovid，以查找相关文献。大多数研究（18 项）侧重于肠道微生物群，而研究口腔（3 项）、阴道（3 项）和胎盘（1 项）的研究则少得多。有一项研究考察了肠道、口腔和阴道微生物群。共识强调了微生物群失调在子痫前期和 HDP 中的潜在作用。特别是在妊娠三个月时，子痫前期与肠道菌群失调有关--缺乏有益的 Akkermansia、双歧杆菌和 Coprococcus，但富含致病的弯曲杆菌和酵母菌，群落 α-多样性较低。同样，先兆子痫患者的阴道和口腔微生物群分别富含细菌性阴道病和牙周病相关物种。在胎盘中也观察到了这种趋势，胎盘中定植有胃肠道、呼吸道和牙周炎相关病原体。因此，慢性促炎状态会对胎盘产生不利影响。然而，这些观察结果需要更多的机理研究，以确定之前免疫功能紊乱的时间和任何因果关系。
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Amy Schumer, Elizabeth A. Bonney, Ethan Harby, Devdoot Majumdar
Problem
Vaccination in pregnancy guards against infection. Maternal antibodies, however, can inhibit antibody production in neonates. We sought to determine the effects of maternal vaccination on neonatal immune response to a SARS-CoV-2 mRNA vaccine.
Method of Study
We hypothesized that mRNA-lipid nanoparticles (LNP) vaccination allows for a de novo neonatal antibody response even in the presence of vertically transmitted maternal antibodies. Female mice were vaccinated with SARS-CoV-2 spike receptor binding domain (RBD) mRNA-LNPs. Mice were then bred, and 21-day-old pups were inoculated with the same mRNA-LNPs. Spike-specific IgG ELISAs were performed using mouse serum. A SARS-CoV-2 spike protein peptide library to perform peptide ELISAs characterized high affinity binding domains within the spike protein. Results were analyzed with one-way ANOVAs with Tukey's multiple comparisons tests.
Results
Compared to pups of unvaccinated dams, there were high levels of spike-specific IgG detected in the pups of vaccinated dams at 3 weeks of life (p < 0.0001). After neonatal vaccination, pups of unvaccinated dams had higher spike-specific serum IgG than pups of vaccinated dams at 12 weeks of life (p < 0.001). Antibody specificity to peptide moieties within spike RBD were similar when comparing a vaccinated dam to her pup at Week 3 of life, with different binding affinities observed in the pups by Week 15 of life.
Conclusions
Pre-existing maternal antibodies may partially blunt the initial neonatal antibody response to mRNA-LNPs vaccination. This vaccine strategy, however, does not prohibit the subsequent development of a broad range of RBD antibody specificities that may be protective.
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