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Aims: The role of depression in subsequent infertility, miscarriage and stillbirth remains unclear. This study aimed to examine the association of a history of depression with these adverse outcomes using a longitudinal cohort study of women across their reproductive life span., Methods: This study used data from participants in the Australian Longitudinal Study on Women's Health who were born in 1973-1978. Participants ( N = 8707) were followed up every 3 years from 2000 (aged 22-27) to 2018 (aged 40-45). Information on a diagnosis of depression was collected from each survey, and antidepressant medication use was identified through pharmaceutical prescription data. Histories of infertility, miscarriage, and stillbirth were self-reported at each survey. Time-lagged log-binomial models with generalized estimating equations were used to assess the association of a history of depression up to and including in a given survey with the risk of fertility issues in the next survey., Results: Women with a history of depression (excluding postnatal depression) were at higher risk of infertility [risk ratio (RR) = 1.34, 95% confidence interval (CI): 1.21-1.48], miscarriage (RR = 1.22, 95%CI: 1.10-1.34) and recurrent miscarriages (≥2; RR = 1.39, 95%CI: 1.17-1.64), compared to women without a history of depression. There were too few stillbirths to provide clear evidence of an association. Antidepressant medication use did not affect the observed associations. Estimated RRs of depression with infertility and miscarriage increased with age., Conclusions: A history of depression was associated with higher risk of subsequent infertility, miscarriage and recurrent miscarriages.

Objective: Thrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey., Methods: This retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed., Results: RPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0-3.0] vs. 4.0 [3.0-5.0]), parity (1.0 [1.0-2.0] vs. 1.0 [0-1.0]), live birth (1.0 [1.0-2.0] vs. 1.0 [0-1.0]), anembryonic pregnancy (0 [0-0] vs. 0 [0-0]), miscarriage (0 [0-1.0] vs. 3.0 [2.0-3.0]), and stillbirth (0 [0-0] vs. 0 [0-0]) numbers differed significantly between the groups (p < 0.05). While no significant differences were determined in MTHFR A1298C, Factor V Leiden, factor II prothrombin G20210A, or homocysteine levels (p > 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027) ., Conclusion: The homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results., (© 2024. The Author(s).)

Background: Previous studies provided inconsistent associations between diabetes mellitus (DM) and miscarriage, recurrent miscarriage (RM). Therefore, this study aims to evaluate the association between DM and miscarriage, specifically RM, through a meta-analysis approach., Methods: We searched for articles published before July 2023 in PubMed and Web of Science databases. STATA 12.0 software was used to compute all the results collected from included studies., Results: DM was associated with a higher risk of miscarriage, RM (miscarriage: odds ratio [OR]/relative risk [RR] = 1.23, 95% confidence interval [CI] 1.13 to 1.34; RM: OR/RR = 1.73, 95% CI 1.55 to 1.94). T1DM was associated with a higher risk of miscarriage (OR/RR = 1.16, 95% CI 1.07 to 1.26). Similarly, T2DM showed a higher risk of miscarriage (OR/RR = 1.44, 95% CI 1.23 to 1.68). Miscarriage, RM were associated with a higher risk of DM (miscarriage: OR/RR = 1.14, 95% CI 1.08 to 1.19; RM: OR/RR = 1.14, 95% CI 1.08 to 1.20). Furthermore, miscarriage was found to be associated with a higher risk of T2DM (OR/RR = 1.08, 95% CI 1.05 to 1.11)., Conclusion: In conclusion, our meta-analysis findings indicate a significant association between DM and miscarriages as well as RM. As a result, women with a history of miscarriage should consider regular monitoring of their metabolic health as a potential benefit. Nevertheless, it is important to note that further research is needed to validate the results of our study and shed light on the biological mechanisms underlying these associations., (© 2024 Japan Society of Obstetrics and Gynecology.)

Introduction: The prevalence of gluten-related disorders, mainly celiac disease (CD) and non-celiac gluten sensitivity (NCGS), varies between 0.6% and 13% in the general population. There is controversial evidence regarding the association of both CD and NCGS with extra-digestive manifestations, including recurrent reproductive failure (RRF), which may have clinical implications., Objective: To study the prevalence of HLA susceptibility alleles for CD/NCGS in a cohort of female patients with RRF from a single reference center and to evaluate the effect of a gluten-free diet on reproductive success., Material and Methods: A retrospective study was conducted on 173 patients with RRF, consecutively attended at the Reproductive Immunology Unit of San Carlos University Clinical Hospital in Madrid. We collected and analyzed the clinical, analytical, and immunological profiles of RRF patients who presented HLA alleles associated with CD and NCGS (HLA DQ2.2, DQ2.5, DQ8, and DQ7.5)., Results: We observed a significantly higher prevalence of HLA alleles associated with CD and NCGS in our RRF cohort compared to the prevalence in the general population (69% vs. 35%-40%, p<0.0001). Only 2.3% of patients met the criteria for a CD diagnosis. In our RRF cohort, HLA-genetic susceptibility for CD/NCGS (HLA-risk group) was associated with a significantly higher rate of hypothyroidism compared to patients without these alleles (HLA-negative group) (48.7% vs. 26.92%, p=0.03). Patients with HLA-genetic susceptibility for CD/NCGS and thyroid disease had a significantly higher success rate in the subsequent pregnancy after management (55% vs. 30%, p=0.002). Two factors were found to be significant in this group: a gluten-free diet (p=0.019) and the use of levothyroxine (p=0.042)., Conclusions: In our cohort of RRF patients, we observed a significantly higher prevalence of HLA susceptibility genes for CD/NCGS compared to the general population, also associated with a higher incidence of thyroid alterations. A gluten-free diet and the use of levothyroxine in cases of thyroid pathology had significant beneficial effects on pregnancy outcomes. We suggest that HLA typing for CD/NCGS and a gluten-free diet, in the presence of risk alleles, can improve pregnancy outcomes in RRF patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de la Fuente-Munoz, Fernández-Arquero, Subbhi-Issa, Guevara-Hoyer, Suárez, Laborda, Sánchez, Ochoa-Grullón, Guzmán-Fulgencio, Villegas, Mansilla, Pérez, Cornudella, Gastañaga-Holguera, Urrutia, García and Sánchez-Ramón.)

Recurrent pregnancy loss (RPL) affects 1-2 % of all couples trying to conceive and is a challenging heterogeneous condition. This study aimed to evaluate the prevalence and impact of various risk factors in patients suffering from RPL. We performed a prospective cohort study including patients at the tertiary RPL Unit in the Capital Region of Denmark between 1st January 2000 and 1st January 2023. The main outcome of the study was the first pregnancy after referral and whether the pregnancy was ongoing at least to the 22nd gestational week. A total of 2555 patients were included in the study, out of whom 1892 patients achieved a pregnancy after referral to the RPL Unit. This resulted in 1103 live births (58.3 %) and 718 pregnancy losses (37.9 %). Maternal age, BMI, smoking status and the number of prior pregnancy losses were negatively correlated with the likelihood of achieving pregnancy. Furthermore, maternal age, prior pregnancy losses, antiphospholipid syndrome (APS) and uterine malformations were associated with reduced birth rates. Patients with secondary RPL had a higher birth rate compared to those with primary RPL, and patients with APS treated with low-molecular-weight heparin (LMWH) demonstrated a significantly increased birth rate compared to untreated APS patients. These findings suggest that certain risk factors significantly impact the likelihood of achieving pregnancy and live birth following RPL, which can be used in patient guidance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL)., Methods: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model., Results: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I 2  = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I 2  = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I 2  = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region., Conclusions: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Question: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?, Summary Answer: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages., What Is Known Already: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL., Study Design, Size, Duration: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals., Participants/materials, Setting, Methods: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth., Main Results and the Role of Chance: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01)., Limitations, Reasons for Caution: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered., Wider Implications of the Findings: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system., Study Funding/competing Interest(s): The research received no specific funding, and the authors declare no competing interests., Trial Registration Number: clinicaltrial.gov NCT05557201., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: It is widely recognized that depression is highly prevalent among women experiencing recurrent spontaneous abortion (RSA), exerting detrimental effects on both the individual and the family., Objective: To assess the depression risk and associated factors among women with RSA., Data Sources: Our search strategy encompassed PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), and WANFANG. The research was conducted in May 2022. We included both randomized and nonrandomized studies that reported the prevalence of depression among women with RSA., Data Extraction and Synthesis: Two independent evaluators reviewed the titles and abstracts, assessed the full-text papers, extracted data from the included studies, and evaluated their quality using the Newcastle-Ottawa Scale (NOS). We performed random-effects meta-analyses to pool the data. Odds ratios (ORs) and standardized mean differences (SMDs) were combined based on effect sizes for binary and continuous outcomes., Main Outcomes: To conduct a meta-analysis to understand the risk of depression in women with RSA who were not treated with psychiatric medications, as well as an analysis of potential factors for depressive symptoms., Results: Out of the initially identified 527 papers, a total of 20 studies (N = 13087) that fulfilled the inclusion criteria were selected. Compared to healthy controls, patients with RSA had a significantly higher risk of depression (OR: 4.26, 95 % confidence interval [CI]: 2.44-7.41; SMD: 0.89, 95 % CI: 0.51-1.26). The occurrence of depression among RSA patients was found to be significantly associated with several factors including the severity of depressive symptoms (OR: 3.82, 95 % CI: 2.22-6.59), number of spontaneous miscarriages (SMD: 0.59, 95 % CI: 0.01-1.18), history of therapeutic termination of pregnancy (SMD: 0.20, 95 % CI: 0.09-0.32), history of live birth (SMD: -0.32, 95 % CI: -0.49--0.15), and duration of marriage (SMD: 0.15, 95 % CI: 0.02-0.27)., Conclusions: In clinical practice, it is crucial to provide appropriate psychological interventions for women undergoing RSA. These individuals face a significantly heightened risk of depression, which exhibits strong correlations with various demographic factors such as the severity of depressive symptoms, history of both spontaneous miscarriages and therapeutic termination of pregnancy, number of live births, and duration of marriage. Consequently, women who are suffering RSA deserves more assistance and emotional support., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The endometrium holds a crucial role in reproduction by supporting blastocyst adhesion, cytotrophoblast invasion and fetal development. Among the various uterine disorders, endometritis, particularly chronic endometritis (CE), has gained attention due to its association with adverse reproductive outcomes (recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and infertility). The association between CE and adverse reproductive outcomes stresses the necessity for comprehensive diagnostic and therapeutic strategies to optimize fertility outcomes and support individuals in their journey towards parenthood., Aim: To explore the relationship between CE and reproductive disorders., Methods: Following PRISMA guidelines, a systematic review and meta-analysis using published data from 1990 to 2024 were carried out., Results: A population of 1,038 women was included. Regarding CE-infertility association, a positive correlation was found, with 19.46% CE rate in infertile women compared to 7.7% in controls (OR: 2.96, 95% CI 1.53-5.72, p 0.001). No significant association was observed between RIF and CE (OR: 1.10, 95% CI 0.26-4.61, p 0.90), CE rates in both groups were relatively comparable, with 6.35% in women with RIF and 5.8% in controls. On the opposite, a strong association between CE and RPL was found, reporting a CE rate of 37.6% in RPL cases compared to 16.4% in controls (OR: 3.59, 95% CI 2.46-5.24, p < 0.00001)., Conclusions: CE appears to be associated to infertility and RPL, while no significant association was noted in cases of RIF., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42024541879., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ticconi, Inversetti, Marraffa, Campagnolo, Arthur, Zambella and Di Simone.)

Smoking during pregnancy is associated with negative reproductive outcome. Less is known about the impact of smoking or previous smoking in women with recurrent pregnancy loss (RPL) which this study aimed to investigate. We included all women <42 years (n=2829) referred to a RPL unit at Copenhagen University Hospital between January 2000 and December 2021 in the cohort with follow-up until June 2022. Patients were categorized as 'smokers at time of referral', 'never-smokers' or 'former smokers'. The main outcomes were pregnancy history prior to referral, prospective pregnancy rate, live birth rate, rates of ectopic pregnancy, and stillbirth. At referral, smokers (n=373) were on average 2.0 years younger (P<0.001) and had experienced significantly more pregnancy losses (P<0.001), and stillbirths (P=0.01) compared to never-smokers (n=2100). Former smokers had a higher risk of stillbirth prior to referral compared to never-smokers but no differences in pregnancy rate or other outcomes. Prospective pregnancy rates were lower for smokers compared with never-smokers (71.8% vs. 77.5%, P=0.02). Live birth rate was 58.0% for the 243 women who smoked at referral compared to 61.4% for the 1488 never-smokers (P=0.32). Stillbirth and ectopic pregnancies were significantly more common for smokers (2.8% vs. 0.4%, P=0.01; 6.0% vs. 2.0%, P<0.008). Women with RPL who smoked at referral were referred younger with a higher number of previous pregnancy losses and stillbirths compared with never-smokers. Fewer smokers achieved a pregnancy after referral but those who did had a similar live birth rate compared to never-smokers, although stillbirths and ectopic pregnancies were more common., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Question: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)?, Summary Answer: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%., What Is Known Already: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL., Study Design, Size, Duration: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023., Participants/materials, Setting, Methods: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria., Main Results and the Role of Chance: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%)., Limitations, Reasons for Caution: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems., Wider Implications of the Findings: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies., Study Funding/competing Interest(s): No specific funding was used. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor obstetrical outcomes and a risk of recurrence as high as 100 %. This meta-analysis examined CIUE prevalence, recurrence, association with autoimmune disorders, reproductive outcomes, pregnancy complications, and the benefits of medical treatments. A systematic review, following PRISMA guidelines, involved a thorough search across multiple databases including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Evidence Based Medical Reviews, and Scopus. Out of 590 initially identified studies, 19 studies were included for both qualitative synthesis and meta-analysis after full-text review. Risk of bias was assessed using appropriate tools: The Risk Of Bias In Non-randomized Studies of Interventions tool was applied to twelve studies, while the Joanna Briggs Institute case series critical appraisal tool was used for seven studies. Our findings confirm that CIUE is a rare condition (0.7 %). CIUE is associated with decreased live birth rates (53 %), increased recurrent pregnancy loss (23 %), fetal loss beyond 22 weeks gestation (25 %), a higher prevalence of autoimmune diseases (14 %), and a recurrence rate of 30 % in subsequent pregnancies. Moreover, individuals with CIUE had higher rates of pregnancy complications, including gestational hypertension (19 %), intrauterine growth restriction (45 %), and preterm births (43 %). No significant improvement in live birth rate was observed among treated CIUE patients; however, caution is warranted when interpreting these findings due to the limited sample size. Future research in CIUE is crucial given its rarity and complexity., Competing Interests: Declaration of Competing Interest Dr. Mohamed A. Bedaiwy: Research grants from Canadian Institutes of Health Research (CIHR) and Ferring Pharmaceutical. He is on the advisory board for AbbVie, Pfizer, and Baxter. Other authors do not have any declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Emerging evidence has shown the association between female reproductive histories (e.g., menarche age, parity, premature and early menopause) and the risk of dementia. However, little attention has been given to infertility and pregnancy loss. To examine the associations of infertility, recurrent miscarriages, and stillbirth with the risk of dementia, this study used data from four cohorts in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. Women with data on at least one of the reproductive exposures of interest, dementia, and all covariates were included. Histories of infertility, miscarriage, and stillbirth were self-reported. Dementia (including Alzheimer's disease) was identified through surveys, aged care, pharmaceutical, hospital, and death registry data. Cause-specific Cox regression models were used to estimate the hazard ratios of dementia, accounting for well-established risk factors of dementia, study variability, and within-study correlation. Overall, 291,055 women were included at a median (interquartile range) age of 55.0 (47.0-62.0) at baseline. During the median (interquartile range) follow-up period of 13.0 (12.0-14.0) years, 3334 (1.2%) women developed dementia. Compared to women without stillbirth, a history of recurrent stillbirths (≥ 2) was associated with 64% higher risk of dementia (adjusted hazard ratio = 1.64, 95% confidence interval: 1.46-1.85). Compared to women without miscarriage, women with recurrent miscarriages (≥ 3) were at 22% higher risk of dementia (adjusted hazard ratio = 1.22, 95% confidence interval: 1.19-1.25). These findings suggest that recurrent stillbirths is a risk factor for dementia and may need to be considered in risk assessment of dementia in women., (© 2024. The Author(s).)

Objective: To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities., Methods: We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding., Results: Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations., Conclusion: The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies., Competing Interests: Conflicts to interest: none to declare.

Objective: This study aimed to identify predictors associated with thyroid function and thromboelastograph (TEG) examination parameters and establish a nomogram for predicting the risk of subsequent pregnancy loss in recurrent pregnancy loss (RPL)., Methods: In this retrospective study, we analyzed the medical records of 575 RPL patients treated at Lanzhou University Second Hospital, China, between September 2020 and December 2022, as a training cohort. We also included 272 RPL patients from Ruian People's Hospital between January 2020 and July 2022 as external validation cohort. Predictors included pre-pregnancy thyroid function and TEG examination parameters. The study outcome was pregnancy loss before 24 weeks of gestation. Variable selection was performed using least absolute shrinkage and selection operator regression and stepwise regression analyses, and the prediction model was developed using multivariable logistic regression. The study evaluated the model's performance using the area under the curve (AUC), calibration curve, and decision curve analysis. Additionally, dynamic and static nomograms were constructed to provide a visual representation of the models., Results: The predictors used to develop the model were body mass index, previous pregnancy losses, triiodothyronine, free thyroxine, thyroid stimulating hormone, lysis at 30 minutes, and estimated percent lysis which were determined by the multivariable logistic regression with the minimum Akaike information criterion of 605.1. The model demonstrated good discrimination with an AUC of 0.767 (95%CI 0.725-0.808), and the Hosmer-Lemeshow test indicated good fitness of the predicting variables with a P value of 0.491. Identically, external validation confirmed that the model exhibited good performance with an AUC of 0.738. Moreover, the clinical decision curve showed a positive net benefit in the prediction model. Meanwhile, the web version we created was easy to use. The risk stratification indicated that high-risk patients with a risk score >147.9 had a higher chance of pregnancy loss (OR=6.05, 95%CI 4.09-8.97)., Conclusions: This nomogram well-predicted the risk of future pregnancy loss in RPL and can be used by clinicians to identify high-risk patients and provide a reference for pregnancy management of RPL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mu, Huo, Wang, Hu and Wang.)

Study Question: Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)?, Summary Answer: Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth)., What Is Known Already: There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition., Study Design, Size, Duration: We conducted a population-based retrospective cohort study of 184 241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198 319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates., Participants/materials, Setting, Methods: Among individuals with at least two recorded live births between 2000 and 2018, 12 321 patients with RPL and 171 920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach., Main Results and the Role of Chance: The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL., Limitations, Reasons for Caution: This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses., Wider Implications of the Findings: The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child., Study Funding/competing Interest(s): This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest., Trial Registration Number: NCT04360564., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Problem: A comprehensive analysis was conducted to explore the scientific output on immune-related recurrent pregnancy loss (RPL) and its key aspects. Despite the lack of clear explanations for most RPL cases, immune factors were found to play a significant role., Method of Study: The study utilized a bibliometric approach, searching the Web of Science Core Collection database for relevant literature published between 2004 and 2023., Results: The collected dataset consisted of 2228 articles and reviews, revealing a consistent increase in publications and citations over the past two decades. The analysis identified the United States and China as the most productive countries in terms of RPL research. Among the institutions, Fudan University in China emerged as the top contributor, followed by Shanghai Jiaotong University. Kwak-kim J was the most prolific author, while Christiansen Ob had the highest number of co-citations. The top 25 co-cited references on diagnosis, treatment, and mechanisms formed the foundation of knowledge in this field. By examining keyword co-occurrence and co-citations, the study found that antiphospholipid syndrome and natural killer cells were the primary areas of focus in immune-related RPL research. Additionally, three emerging hotspots were identified: chronic endometritis, inflammation, and decidual macrophages. These aspects demonstrated increasing interest and research activity within the field of immune-related RPL., Conclusions: Overall, this comprehensive bibliometric analysis provided valuable insights into the patterns, frontiers, and focal points of global scientific output related to immune-related RPL., (© 2024 Japan Society of Obstetrics and Gynecology.)

Objective: The primary purpose of this study was to examine whether pregnant women with a history of recurrent pregnancy loss (RPL) are more likely to experience moderate-to-severe depression, anxiety, or stress symptoms than pregnant women without a history of RPL. The secondary purpose was to determine whether women with prior RPL experienced more unfavorable pregnancy outcomes if they had depression, anxiety, or stress., Methods: A prospective case-control study was conducted that included 47 pregnant women with a history of RPL and 94 pregnant women without prior RPL. Participants 20 weeks of gestation or earlier were included. Both groups completed the Depression, Anxiety, and Stress Scale (DASS-21), and were followed up until delivery to determine the pregnancy outcomes. Multivariate logistic regression was used to compare adverse pregnancy outcomes., Result: Among the 47 women with prior RPL, 10 had primary RPL (two or more miscarriages without a successful pregnancy) and 37 secondary RPL (two or more miscarriages with a history of successful pregnancy). RPL was significantly associated with moderate-to-severe levels of depression ( P < .001), anxiety ( P < .001), and stress ( P < .001). Among the RPL group, high stress level was significantly associated with repeat miscarriage (adjusted odds ratio (AOR) = 5.28, 95%CI = 1.25-100.0, P = .03) and preterm labor (AOR = 6.07, 95%CI = 1.61-100.0, P = .04). Depression and anxiety were not associated with adverse pregnancy outcomes., Conclusion: Pregnant women with a history of RPL had considerably higher rates of moderate-to-severe depression, anxiety, and stress. Repeat miscarriage and preterm labor were considerably higher among pregnant women with RPL who were experiencing high stress levels at baseline., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients., Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed., Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects., Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Problem: To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM)., Methods: Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat., Results: For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837)., Conclusions: Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3., (© 2024 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Problem: Studies on subsequent pregnancy loss prediction models specific for recurrent pregnancy loss (RPL) patients are very limited. This study aims to develop a risk predictive model based on the immunological parameters for the subsequent pregnancy loss risk in northwest Chinese RPL patients., Method of Study: Totally of 357 RPL patients recruited from Lanzhou University Second Hospital were included in this retrospective study. Univariate analysis was performed on RPL patients with outcomes of live birth or pregnancy loss. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables among baseline and clinical characteristics and to develop a pregnancy loss risk prediction model with all 357 RPL patients. The area under the curve (AUC), calibration curve and decision curve analyses were used to evaluate the performance of the prediction model; moreover, 10-fold cross-validation was used for internal validation., Results: Ten factors of maternal age, age of menarche, previous pregnancy loss, IL-10, complement 4, IgA, antiprothrombin antibody IgG/IgM, rheumatoid factor IgA, and lupus anticoagulant (LA) 1/LA2 ratio were finally selected as variables for the prediction model of pregnancy loss risk. The AUC value and Hosmer-Lemeshow test p-value of the model were .707 and .599, respectively, indicating a satisfactory discrimination and calibration performance. Moreover, the clinical decision curve suggested this prediction model have a good positive net benefit., Conclusions: This is the first prediction model for the risk of subsequent pregnancy loss in northwest Chinese women with RPL, providing a user-friendly tool to clinicians for the early prediction and timely management of RPL patients., (© 2024 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Objective: This study aimed to investigate the association between a history of recurrent spontaneous abortion (RSA) and adverse outcomes in women with spontaneous conception., Methods: A search strategy from the inception to March 3, 2023 was run in PubMed, Embase, Cochrane Library, and Web of Science databases. The odds ratio (OR), and the 95% confidence interval (CI) or point estimation were used as the evaluation indexes. Each outcome measure tested was assessed for heterogeneity using the Cochran Q test. Sensitivity analyses were performed to test the credibility of the meta-analysis results., Results: Fifteen studies involving 1 475 389 pregnant women were included. A history of RSA was associated with gestational diabetes (OR: 2.21, 95% CI: 1.70-2.87, p < 0.001), preeclampsia (OR: 2.06, 95% CI: 1.49-2.86, p < 0.001), placenta previa (OR: 1.82, 95% CI: 1.09-3.02, p = 0.021), placental abruption (OR: 1.67, 95% CI: 1.36-2.06, p < 0.001), miscarriage (OR: 6.37, 95% CI: 3.83-10.57, p < 0.001), preterm birth (OR: 1.80, 95% CI: 1.36-2.37, p < 0.001), cesarean section (OR: 1.47, 95% CI: (1.13-1.91, p = 0.004), perinatal death (OR: 2.24, 95% CI: 1.39-3.60, p = 0.001), and neonatal intensive care unit admission (OR: 1.39, 95% CI: 1.01-1.92, p = 0.047). However, the associations of a history of RSA with gestational hypertension, small for gestational age, fetal anomalies, fetal growth restriction, and postpartum hemorrhage were not observed., Conclusion: This meta-analysis indicates a history of RSA was associated with increased risks of several adverse outcomes in pregnant women with spontaneous conception., (© 2023 Japan Society of Obstetrics and Gynecology.)

Pregnancy is a state of happiness and hope not only for a woman but for her family as well as near and dear ones. However, this phase of happiness comes shattering down for some couple who are not able to successfully complete pregnancy and end up losing a baby in the early stages of pregnancy. Recurrent pregnancy loss (RPL) is prevalent among Omani women and the psychosocial impact of RPL is heavy upon these young women devastating their overall quality of life. Researchers conducted a cross sectional survey among 184 Omani women who had a history of recurrent pregnancy loss in a pioneering teaching tertiary care hospital. Data collection done from using a self-reported questionnaire to assess the depression, anxiety and RPL associated stress of women with history of RPL The mean age of women with RPL was 34.05 and 81% reported 2-3 pregnancy loss. Participants reported higher mean scores of depression (9.94), Anxiety (10.32) and fertility related stress (30.28). Women with multiple pregnancy losses (above 3) reported higher level of anxiety which was significant at (p<0.05%) The findings from current study also indicated that women with RPL experience higher levels of depression, anxiety, and fertility related stress., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Background: The etiology of recurrent spontaneous abortion (RSA) remains elusive despite specific investigations affirming the association between RSA and thyroid autoimmunity (TAI). This study explores the immunological and metabolic profiles of RSA patients exhibiting positive thyroid antibodies and their connection with the rates of first-trimester miscarriage and live births. The aim is to provide further guidance for clinical interventions., Methods: A retrospective analysis included 478 women with RSA. Thyroid profile, thyroid peroxidase antibodies, and anti-thyroglobulin antibodies were measured in all participants. The clinical characteristics and pregnancy outcomes of RSA women were compared between thyroid autoimmunity (TAI)-positive and TAI-negative patients. Significant factors associated with adverse pregnancy outcomes and risk prediction models were explored in TAI-positive patients. Correlation analysis was used to identify specific metabolic or immune biomarkers associated with thyroid autoantibodies., Results: The prevalence of TAI was 18.6%. Compared with women without TAI, the thyroid-stimulating hormone (TSH) concentration of TAI-positive RSA was significantly higher (2.80 ± 2.98 vs 1.89 ± 1.17, p=0.006). After 28 weeks, the live birth rate of the TAI-positive group was lower than that of the TAI-negative group, with statistical significance (p<0.05). The immune biomarkers that differed between RSA women with live births and those with first-trimester miscarriages were complement C4 and interleukin-6, respectively, in TAI-negative and TAI-positive women. Then, a risk prediction model for first-trimester miscarriage was constructed for TAI-positive women with an AUC of 0.81. Finally, some factors related to thyroid peroxidase antibody (TPO-Ab) levels were explored, and it was found that TPO-Ab levels were positively correlated with free thyroxine and negatively correlated with 25 hydroxyvitamin D, interleukin-4, and fasting blood glucose in RSA patients., Conclusion: TAI-positive RSA patients have higher first-trimester miscarriage rates and a lower live birth rate, which may be related to metabolic immune shifts in TAI-positive RSA patients., Competing Interests: Author HY is employed by the company Dian Diagnostics Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Box 1Final optimal prediction model to facilitate individual predictions.The equation representing the prediction model for assessing the risk of first-trimester miscarriage in women with TAI was derived from a logistic regression model incorporating factors determined through random forest ranking: percent risk=exp(Y)/(1+exp(Y))*100Where Y = (-6.65) + (0.16 * age in years) - (0.48 * interleukin 6 in pg/ml) - (0.03 * total bilirubin in umol/L) + (1.27* total triiodothyronine in mIU/L) + (0.43 * interferon-γ in pg/ml) + (0.31 * number of previous miscarriages) -(0.01* complement C1q in g/l)., (Copyright © 2024 Zhang, Song, Yuan and Cai.)

Background: Inherited thrombophilia, mainly the Factor V Leiden (FVL) and Prothrombin mutation (PTM) are the most risk factors for venous thrombosis especially during pregnancy and was strongly associated with recurrent pregnancy loss (RPL), a devastating reproductive problem that affects more than 1% of couples who are trying to conceive. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations., Objectives: In this study we evaluated the presence inherited thrombophilia amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling., Methods: DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of mutation., Results: FVL and PTM were detected in 5.7 % and 2.9% respectively; in women with a particular history of early fetal loss and thrombotic events., Conclusion: This study emphasizes the importance of testing for FVL and FIIM in women with RPL; mainly in the context of thrombotic events. Multi-center collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of inherited thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 Frikha R et al.)

Objective: To evaluate the risk of metabolic syndrome (MS) after recurrent pregnancy loss (RPL) using UK Biobank data. A history of pregnancy loss is associated with the development of cardiovascular diseases in the future. However, the association between RPL and subsequent MS is poorly understood. Therefore, we aimed to check the risk of MS after RPL., Design: The study population was divided into 2 groups according to reproductive history: women with a history of RPL and women without a history of RPL. Recurrent pregnancy loss was defined as 2 or more spontaneous miscarriages, and MS was defined as at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, high-blood pressure, and hyperglycemia., Setting: UK Biobank resource., Patients: The UK Biobank is a prospective cohort study that enrolled individuals aged between 40 and 69 years whose medical and reproductive histories were retrieved at enrollment. In this cohort, only women with a history of at least one pregnancy were selected., Interventions: Recurrent pregnancy loss., Main Outcome Measures: The primary outcome was the prevalence of MS. The secondary outcomes were 5 diagnostic components of MS., Results: We analyzed 228,674 women, including 15,702 with a history of RPL and 212,972 without a history of RPL. Women with a history of RPL have a higher prevalence of MS between the ages of 40 and 60 years (33.0% vs. 31.5%). After adjusting for covariates (age, race, number of live births, early menopause, smoking, alcohol consumption, and physical activity), the increased risk of MS after RPL remained significant (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.15). Furthermore, in the analysis of the 5 diagnostic components of MS, a history of RPL significantly increased the risk of abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hyperglycemia., Conclusion: Middle-aged women with a history of RPL have an increased risk of MS., Competing Interests: Declaration of interests J.H.B. has nothing to disclose. Y.M.J. has nothing to disclose. J.L. has nothing to disclose. M.S. has nothing to disclose. C.W.P. has nothing to disclose. J.S.P. has nothing to disclose. J.K.J. has nothing to disclose. D.K. has nothing to disclose. S.K.K. has nothing to disclose. S.M.L. has nothing to disclose., (Copyright © 2023. Published by Elsevier Inc.)

This manuscript reports on the prevalence of early pregnancy loss. The impact of improved pregnancy diagnosis and influence of increased age and body mass index at first birth are discussed., Competing Interests: Declaration of interests H.G.G. has nothing to disclose. D.B.M. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Miscarriage and recurrent miscarriage affect a significant proportion of every population with research consistently showing it results in profound and often prolonged psychological impacts. Despite the serious psychological impacts, support for miscarriage remains grossly inadequate. There are many ways to ameliorate the impact of these losses, which are not difficult, expensive, or time consuming. At a basic level, people want and need acknowledgment and validation of their grief and loss and greater information provision at the time of loss. A clear discrepancy also exists between the bereavement care offered by health care providers and the care wanted and needed by those affected, that must be addressed as a matter of urgency. At a health care system level, the collection of national miscarriage data must begin, to allow for a true understanding of the socioeconomic cost of miscarriage and the burden of early pregnancy loss on individuals, families, and our social systems. Furthermore, to direct research funding appropriately, establishing national research funding priorities for miscarriage support, as they have in the United Kingdom, is vital in assisting researchers and other key stakeholders to effectively target research in areas that are likely to have the greatest public health benefit. Consumers, health practitioners, and policymakers could achieve a lot for many with just a little commitment to change., Competing Interests: Declaration of interests J.E.B. has nothing to disclose. M.T.-S has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Miscarriage is a relatively common occurrence with many knowns and unknowns and a profound psychological impact on individuals and couples. The editors felt it was time to publish a series of overviews for Views and Reviews on both sporadic miscarriage and recurrent miscarriage. The series starts with the prevalence of miscarriage and recurrent miscarriage and subsequently describes the psychological impact, what we know of the genetics, whether uterine natural killer cells may play a role, the association with infections, and potential interventions., Competing Interests: Declaration of interests M.v.W. has nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recurrent miscarriage affects 1-2% of the population, and the literature has focussed on causes, treatment, and live birth rate., Aim: This study aimed to assess the reproductive outcomes for patients who attended a specialist recurrent miscarriage clinic for investigation and treatment., Methods: Prospective analysis of all patients who attended a recurrent miscarriage clinic from January 2014 to January 2021., Results: Of the 488 patients who attended a specialist clinic, 318 had a further pregnancy with 299 included in this study. The median age was 37 years, with 55.6% having a previous live birth. The subsequent live birth rate was 75.3%, 22.0% had a further pregnancy loss, 1.7% had an ongoing pregnancy, and 1% attended another institution after the second trimester. The rate of preeclampsia was 2.2%, pregnancy-induced hypertension was 2.2%, fetal growth restriction was 5.3%, preterm birth ≤ 34 weeks was 1.8%, and preterm birth > 34 weeks < 37 weeks was 6.6%., Conclusion: Patients who attend a dedicated recurrent miscarriage clinic for investigation and treatment have a high live birth rate in a subsequent pregnancy. A subsequent pregnancy following recurrent pregnancy loss does not appear to be associated with an increased risk of adverse pregnancy outcomes., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Purpose: To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among patients in an academic fertility clinic., Methods: In this retrospective cohort study, data from patients who underwent endometrial sampling (ES) for CE evaluation at a single academic institution from 2014 to 2020 were collected and analyzed. Rates of CE were compared by indication for ES including recurrent pregnancy loss (RPL), implantation failure (IF), and recent first-trimester pregnancy loss. Treatment and pregnancy outcomes were also evaluated., Results: Six hundred fifty-three individuals underwent ES to evaluate for CE. The overall prevalence of CE was 28.5%; when stratified by indication, the prevalence of CE was 66.2% for recent first-trimester loss, 27.9% for RPL, and 13.1% for IF (p < .001). Of those with CE, 91.9% received antibiotics, most commonly doxycycline (76.0%). CE clearance was not significantly different when doxycycline was compared to all other regimens (71.3% vs. 58.8%, p = .17), and 68.5% of patients cleared CE after one course of antibiotics. Following two antibiotic courses, CE was cleared in 88.3% of patients. Live birth rates (LBRs) were higher for those with cleared CE compared to patients with untreated CE (34.1% vs. 5.6%, p = .014) and similar for those with cleared CE versus those without CE (34.1% vs. 29.3%, p = .297)., Conclusion: CE is common among patients with infertility, particularly those with a recent first-trimester loss. Treatment and clearance of CE were associated with higher LBRs; however, persistent CE was common despite treatment with antibiotics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The objective of this study was to characterize the relationship between embryonic chromosomal errors in the products of conception (POC) and maternal age, gestational age (GA) of pregnancy loss, and findings on routine recurrent pregnancy loss (RPL) workup. This is a retrospective cohort study of women with a history of ≥ 2 pregnancy losses and who underwent cytogenetic testing on the POC of a subsequent pregnancy loss at an academic tertiary RPL referral center. The association between the odds of embryonic chromosomal errors in POC and maternal age, GA of pregnancy loss, as well as RPL work up findings was investigated. A total of 1107 miscarriages were analyzed from 741 women. There was an overall linear relationship between embryonic chromosomal errors and maternal age, with a nearly twofold increase in the odds of chromosomal error with every 5-year increase in maternal age (P < 0.0001). The association between chromosomal errors and GA was also linear (P = 0.0001), with most losses having no chromosomal errors after 13 weeks' gestation. Women with ≥ 1 positive findings on routine RPL diagnostic workup had lower odds of embryonic chromosomal errors compared to those with a normal workup [OR 0.57 (95% CI = 0.41-0.80)]. Notably, the estimated prevalence of chromosomal error remained high (> 60%) in women ≥ 35 years old irrespective of findings on routine evaluation. While embryonic chromosomal errors were associated with advanced maternal age, early GA of loss, and a negative routine RPL evaluation, the prevalence of chromosomal errors remained high in all subpopulations. These findings suggest that primary cytogenetic testing on POCs should be offered at the time of second and subsequent pregnancy losses in all RPL patients., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: To evaluate the prevalence of abnormal endocrine dysfunction for recurrent pregnancy loss (RPL) amongst patients with two versus three or more pregnancy losses., Methods: This cross-sectional study retrospectively collected pre-pregnancy data of 537 women diagnosed with RPL in Shengjing Hospital of China Medical University from 2017 to 2022, including the baseline data of patients and the test results of endocrine factors. Several endocrine dysfunction included in this study were: thyroid dysfunction, obesity, hyperprolactinemia, polycystic ovary syndrome and blood glucose abnormality. Furthermore, vitamin D level were collected to study its relationship with endocrine dysfunction. Finally, we subdivided the patients according to the number of previous pregnancy loss and compared the prevalence of endocrine dysfunction between subgroups., Results: Among 537 RPL patients, 278 (51.8%) patients had abnormal endocrine test results. The highest incidence of endocrine dysfunction was thyroid dysfunction (24.39%, 131/537), followed by hyperprolactinemia (17.34%, 85/490), obesity (10.8%, 58/537), polycystic ovary syndrome (10.50%, 56/533), and abnormal blood glucose (5.29%, 27/510). Only 2.47%(13/527) of patients have vitamin D level that reach the standard. After subdividing the population according to the number of pregnancy loss, we did not find that the incidence of endocrine dysfunction (P=0.813), thyroid dysfunction (P=0.905), hyperprolactinemia (P=0.265), polycystic ovary syndrome (P=0.638), blood glucose abnormality (P=0.616) and vitamin D deficiency (P=0.908) were different among patients with two versus three or more pregnancy losses. However, obesity (P=0.003) was found more frequently observed in patients with more times of pregnancy loss., Conclusion: The prevalence of endocrine dysfunction in RPL population is high. There is no difference in the prevalence of endocrine dysfunction, except for obesity, among patients with two or more pregnancy losses, which may suggest investigations of endocrine dysfunction when patients have two pregnancy losses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Du, Zhou, Li, Shen, Liu, Liu and Qiao.)

Currently, obesity is considered a global public health problem. It is the main risk factor for noncommunicable diseases and reproductive complications, such as recurrent miscarriage (RM). RM affects approximately 1% of couples of reproductive age, and recent studies suggest that its prevalence is increasing. Immunological abnormalities may be responsible for a significant number of cases of unexplained RM. Obesity is recognized as a chronic low-grade inflammatory condition. The accumulation of fat in obese adipose tissue promotes changes in the local and systemic immune response. Adipokines, exosomes, micro-RNAs, lipids, and other factors released or secreted by adipose tissue are responsible for the interconnection between obesity and the immune system. Obesity-induced dysregulation of the innate and acquired immune response is also involved in the immunopathology of pregnancy loss in patients with unexplained RM. Therefore, understanding the communication pathways between maternal adipose tissue and the immune response in women living with obesity and RM is an important objective. Thus, diagnostic tools and new immunomodulatory therapies may be proposed for the management of patients with concurrent obesity and RM., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed to elucidate the etiologies of and risk factors for recurrent pregnancy loss (RPL) according to fertile ability, focusing on the differences between superfertile and subfertile patients. This retrospective observational study included 828 women with RPL between July 2017 and February 2020. Patients were divided into three groups based on time to pregnancy (TTP): superfertile (SUP) (TTP ≤3 months for all previous pregnancies), subfertile (SUB) (previous TTP ≥12 months and use of assisted reproductive technology [ART]), and Normal (N) (TTP >3 or <12 months without ART). All patients were assessed for uterine anatomy, antiphospholipid antibodies (APAs), thyroid function, and thrombophilia. Of the 828 patients, 22%, 44%, and 34% were assigned to the SUP, SUB, and N groups, respectively. The mean ages were 33.9, 38.2, and 35.9 years in the SUP, SUB, and N groups, respectively, revealing a significant difference (P < 0.001). The anti-CL β2GPI antibody positivity rate was significantly higher in the SUP group (4.6%) than in the N group (0.8%; P = 0.016). The prevalence of APA positivity was lowest in the N group. Overall, the clinical characteristics and etiologies of RPL associated with superfertility and subfertility were strikingly similar, with comparable positivity rates after adjusting for maternal age. Further investigation including chromosomal analysis of products of conception is needed to elucidate the clinical impact of differences in fertility on patients with RPL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To examine the associations between a history of recurrent miscarriage (RM) and adverse obstetric and perinatal outcomes in the subsequent pregnancy that progressed beyond 24 weeks., Design: Retrospective cohort study., Setting: A large tertiary maternity hospital., Patient(s): All women who booked for antenatal care and delivery between January 2014 and August 2021 were recorded. The study was limited to women with a singleton pregnancy, and to avoid intraperson correlation, we selected the first record of delivery from each mother in the study, leaving 108,792 deliveries for analysis. Obstetric and perinatal outcomes were compared among 1994 women (1.83%) with a history of ≥2 miscarriages (RM), 11,477 women (10.55%) with a history of 1 miscarriage, and 95,321 women (87.62%) with no history of miscarriage, respectively., Intervention(s): Women with a history of ≥2 miscarriages or RM., Main Outcome Measure(s): Obstetric complications included gestational diabetes mellitus, preeclampsia (subclassified as preterm and term preeclampsia), placenta previa, placenta accreta, and fetal distress. Perinatal outcomes included emergency cesarean section, elective cesarean section, induction, postpartum hemorrhage, preterm birth, stillbirth, Apgar score <7 at 5 minutes, neonatal asphyxia, neonatal sex, congenital; malformation, low birth weight, and neonatal death., Result(s): After adjusting for relevant confounders, there was an increased risk of adverse obstetric and perinatal outcomes in a subsequent pregnancy for women with a history of RM, specifically for placental dysfunction disorders: preterm preeclampsia (risk ratio [RR] = 1.58; 95% confidence interval [CI], 1.03-2.32), preterm birth (RR = 1.34; 95% CI, 1.15-1.54)], and abnormal placentation, that is placenta previa (RR = 1.78; 95% CI, 1.36-2.28), and placenta accreta (RR = 4.19; 95% CI, 2.75-6.13)., Conclusion(s): Significant associations existed between a history of RM and the occurrence of adverse obstetric and perinatal outcomes including placental dysfunction disorders and abnormal placentation. These findings may contribute to the early detection and appropriate intervention for placenta-associated diseases in women with a history of RM, with the goal of avoiding or reducing the associated detrimental effects., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Maternity services underwent much change during the COVID-19 pandemic. Research on the impact on miscarriage care and experiences during this time is sparse. Within a national evaluation of recurrent miscarriage care, we qualitatively explored stakeholder views and experiences of recurrent miscarriage services in Ireland. This study describes the impact of the COVID-19 pandemic on those experiences and perceptions of care., Methods: People with professional and lived experience of recurrent miscarriage and service engagement were actively involved in this qualitative study from idea generation to analysis and reporting. We recruited women and men with two or more consecutive first-trimester miscarriages, and people involved in the management/delivery of recurrent miscarriage services and supports. We used purposive sampling to ensure that perspectives across disciplinary or lived experience, geographical, and health service administrative areas, were included. We conducted semi-structured interviews, virtually all due to COVID-19 restrictions, between June 2020 and February 2021. These were audio-recorded, and data were transcribed, and subsequently analyzed using reflexive thematic analysis., Results: We interviewed 42 service providers and 13 women and 7 men with experience of recurrent miscarriage. We actively generated two central themes during data analysis. The first-'Disconnected'-describes how many women navigated miscarriage diagnosis and management and care in subsequent pregnancies alone; many felt that this resulted in increased trauma. At the same time, men struggled with not being present to support their partners and described feeling disconnected. The second theme highlighted 'The perceived dispensability of recurrent miscarriage services and supports'. Some service providers felt that service reduction and redeployment demonstrated a lack of value in the service. Virtual clinics facilitated access to services, but a preference for in-person care was highlighted., Conclusion: Our analysis provides rich insights into the significant impacts that the COVID-19 pandemic has had on the way recurrent miscarriage care is provided and experienced, with important implications for early pregnancy, miscarriage and recurrent miscarriage care. Services have undergone significant changes and, while these may be temporary, how services should be delivered in the future requires consideration, particularly given the deficits in care and care experiences highlighted prepandemic., Patient or Public Contribution: Members of the multidisciplinary RE:CURRENT Project Research Advisory Group (including four parent advocates, two of whom are co-authors on this article) were actively involved throughout the study, including the generation of topic guides and the refining of themes., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The steady-state gut microbiome not only promotes the metabolism and absorption of nutrients that are difficult to digest by the host itself, but also participates in systemic metabolism. Once the dynamic balance is disturbed, the gut microbiome may lead to a variety of diseases. Recurrent pregnancy loss (RPL) affects 1-2% of women of reproductive age, and its prevalence has increased in recent years. According to the literature review, the gut microbiome is a new potential driver of the pathophysiology of recurrent abortion, and the gut microbiome has emerged as a new candidate for clinical prevention and treatment of RPL. However, few studies have concentrated on the direct correlation between RPL and the gut microbiome, and the mechanisms by which the gut microbiome influences recurrent miscarriage need further investigation. In this review, the effects of the gut microbiome on RPL were discussed and found to be associated with inflammatory response, the disruption of insulin signaling pathway and the formation of insulin resistance, maintenance of immunological tolerance at the maternal-fetal interface due to the interference with the immune imbalance of Treg/Th17 cells, and obesity.

Objective: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics., Method: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher's exact test and logistic regression., Results: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41-2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79-4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84-2.94; 3 times: OR, 1.59; 95% CI, 1.23-2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15-1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87-8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00-12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics., Conclusion: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Changes of platelet distribution width (PDW) have been observed in women with unexplained recurrent pregnancy loss (URPL). However, relevant previous studies showed inconsistent results. We performed a meta-analysis to comprehensively evaluate the association between PDW and URPL., Methods: Observational studies reporting the difference of PDW between women with and without URPL were retrieved by searching PubMed, Embase, Web of Science, Wanfang, and CNKI. A random-effect model was used to pool the results by incorporating potential heterogeneity., Results: Eleven case-control studies with 1847 women with URPL and 2475 healthy women were included. Age was matched for all studies between cases and controls. Pooled results showed women with URPL had significantly increased level of PDW (mean difference [MD]: 1.54%, 95% CI: 1.04 to 2.03, p < 0.05; I 2 =77%). Subgroup analysis showed consistent result for URPL defined as ≥ 2 (MD: 1.45%, p = 0.003) and ≥ 3 (MD: 1.61%, p < 0.001) failed clinical pregnancies, and in studies compared to women with normal pregnancy (MD: 2.02%, p < 0.001) and non-pregnant healthy women (MD: 1.34%, p < 0.001). Results of the meta-analysis also showed that increment of PDW was associated with higher odds of URPL (per 1 unit, odds ratio: 1.26, 95% CI: 1.17 to 1.35, p < 0.001; I 2 = 0%)., Conclusions: Women with URPL had significantly increased levels of PDW compared to healthy women without URPL, which suggest that higher PDW may predict the risk of URPL., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research Question: Is anti-Müllerian hormone (AMH) associated with live birth rate (LBR) in women with unexplained recurrent pregnancy loss (RPL)?, Design: Cohort study of women with unexplained RPL attending the RPL Unit, Copenhagen University Hospital, Denmark, between 2015 and 2021. AMH concentration was assessed upon referral, and LBR in the next pregnancy. RPL was defined as three or more consecutive pregnancy losses. Regression analyses were adjusted for age, number of previous losses, body mass index, smoking, treatment with assisted reproductive technology (ART) and RPL treatments., Results: A total of 629 women were included; 507 (80.6%) became pregnant after referral. Pregnancy rates were similar for women with low and high AMH compared to women with medium AMH (81.9, 80.3 and 79.7%, respectively) (low AMH: adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.84-2.47, P = 0.18; high AMH: aOR 0.98, 95% CI 0.59-1.64, P = 0.95). AMH concentrations were not associated with live birth. LBR was 59.5% in women with low AMH, 66.1% with medium AMH and 65.1% with high AMH (low AMH: aOR 0.68, 95% CI 0.41-1.11, P = 0.12, high AMH: aOR 0.96, 95% CI 0.59-1.56, P = 0.87). Live birth was lower in ART pregnancies (aOR 0.57, 95% CI 0.33-0.97, P = 0.04) and with higher numbers of previous losses (aOR 0.81, 95% CI 0.68-0.95, P = 0.01)., Conclusion: In women with unexplained RPL, AMH was not associated with the chances of live birth in the next pregnancy. Screening for AMH in all women with RPL is not supported by current evidence. The chance of live birth among women with unexplained RPL achieving pregnancy by ART was low and needs to be confirmed and explored in future studies., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients demonstrated that an increase in Ureaplasma species in the endometrium raised the risk of miscarriage with an euploid karyotype. While endometrial sampling is invasive, cervicovaginal sampling is not. We compared vaginal and cervical microbiomes with a 16 S ribosomal RNA sequence between 88 patients with unexplained RPL and 17 healthy women with no history of miscarriage. We prospectively assessed risk factors for maternal colonization at a subsequent miscarriage without an aneuploid karyotype in patients. Cervicovaginal bacteria were dominated by Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae and Bifidobacterium breve in Japanese population. The proportions of Delftia and unknown bacteria in the cervix were significantly higher in patients with RPL than in controls. Streptococcus, Microbacterium, Delftia, Anaerobacillus and Chloroplast in the cervix were significantly higher in patients with a history of chorioamnionitis compared to the controls. The abundance of Cutibacterium and Anaerobacillus in the cervix was significantly higher in patients who had subsequently miscarried compared to those who gave birth. The miscarriage rate in patients with higher proportions of both Cutibacterium and Anaerobacillus (66.7%, 2/3) was significantly greater than that of patients who lacked these bacteria (9.2%, 6/65, adjusted odds ratio 16.90, 95% confidence interval 1.27-225.47, p = 0.032). The presence of certain bacteria could be a predictor of subsequent miscarriage without an aneuploid karyotype. The cervicovaginal microbiome might be useful for investigating a possible cause of RPL., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Serum Anti-Müllerian Hormone (AMH) levels have been shown to be lower among women who have experienced recurrent pregnancy loss (RPL) compared with the general population. However, it is unclear whether it can predict livebirth. This study aims to determine whether AMH can predict the likelihood of a livebirth in women with RPL., Study Design: Prospective analysis of a consecutive cohort of women undergoing investigation for RPL in a tertiary referral centre over a seven year period (August 2014 -December 2021). Analysis was performed using descriptive statistics, chi-square models and logistic regression models adjusting for maternal age and previous livebirth. Exclusion criteria for the regression analysis included abnormal parental karyotype and abnormal pelvic ultrasound scan. Pregnancy outcome was defined as livebirth or further pregnancy loss., Results: There were 488 women who underwent investigation of RPL during the study period. Of these, 65.2% (n = 318) conceived following attendance at the clinic. The majority of these women (69.4%, n = 221) proceeded to have a livebirth. There were no differences in median AMH levels between the livebirth group and the further pregnancy loss group (11 pmol/L vs 9 pmol/L respectively (p = 0.083). AMH did not affect clinical pregnancy rates (p = 0.77, 95% CI = 0.99 [0.98, 1.01]) or pregnancy outcome (p = 0.30, 95% CI = 1.01 [0.99, 1.04]). Abnormal pelvic ultrasonography (p = 0.04) and an abnormal parental karyotype (p = 0.04) were associated with an increased likelihood of a subsequent pregnancy loss., Conclusion: Although AMH levels may have some utility in counselling of some couples with RPL, these contemporaneous data indicate that low AMH does not negatively influence subsequent pregnancy outcome in women with recurrent pregnancy loss., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To test the hypothesis claiming an association between human papilloma virus (HPV) sperm infection and idiopathic recurrent pregnancy loss (RPL)., Design: Multicenter retrospective case-control study., Setting: Three university hospitals., Patient(s): Cases included men belonging to couples affected by first trimester idiopathic RPL. Controls included men belonging to couples with proven fertility and no history of pregnancy loss; RPL was defined as the previous loss of 2 or more pregnancies. Couples were defined as "fertile" if they achieved a full-term pregnancy within the year before enrollment in the study. All participants conceived without assistance., Main Outcome Measure(s): The association between HPV DNA sperm infection, as identified using polymerase chain reaction, and RPL., Results: The HPV DNA sperm infection was detected in 23 of 117 cases (20%; 95% confidence interval [CI]: 13%, 28%) and in 3 of 84 controls (4%; 95% CI; 1%, 10%) (P<.001). A comparison across baseline characteristics and multiple regression analysis did not identify any potentially confounding factors. Multivariate regression models showed a significant association between HPV DNA sperm infection and RPL (adjusted odds ratio, 7.44; 95% CI: 2.08, 26.58; P=.002 [Model 1]; adjusted odds ratio, 8.96; 95% CI: 2.41, 33.44; P=.001 [Model 2])., Conclusions: The prevalence of HPV sperm infection was significantly higher in couples affected by RPL than in their fertile counterparts. Notably, the semen sample was infected by HPV in approximately 1 out of 5 patients., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Chronic deciduitis (CD) is defined as the presence of lymphocytes or plasma cells in decidual tissue. CD suggests the presence of chronic endometritis (CE) which is associated with recurrent pregnancy loss (RPL). In this study, we examined the role CD plays in RPL patients with aneuploid and euploid miscarriage. The frequency of CD in 49 RPL patients (22 euploid and 27 aneuploid miscarriages) and 17 control women was assessed and the subsequent live birth rate (LBR) in the presence and absence of CD were compared. When only one CD138-positive endometrial stromal plasma cell (ESPC) was found per high-power field (HPF), we diagnosed small-positive CD (Grade 1). When a cluster of two or more CD138-positive ESPCs was found per HPF, we diagnosed it as CD Grade 2. The prevalence of Grade 1 was 18.2% (4/22) in patients with euploid miscarriage, 37.0% (10/27) in patients with aneuploid miscarriage and 23.5% (4/17) in control women. The prevalence of Grade 2 was 45.5% (10/22) in patients with euploid miscarriage, 55.6% (15/27) in patients with aneuploid miscarriage and 23.5% (4/17) in control women. There was a significant difference in the prevalence of CD (p = 0.015). The LBR of patients with CD was similar to that of patients without CD. CD was associated with RPL, especially in patients with aneuploid miscarriage. However, since there was no difference in the LBR of patients with or without CD in the next pregnancy, it was unclear whether CD was a contributing cause of RPL., Competing Interests: Conflicts of interest None of the authors have a conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This systematic review and meta-analysis were designed to identify possible correlations between isolated serum antinuclear antibody (ANA) and (i) infertility in the context of in-vitro fertilization (IVF), (ii) idiopathic recurrent pregnancy losses (RPL), and (iii) second/ third trimester pregnancy complications. We performed a systematic review and meta-analysis of the literature in PubMed Library database from inception to March 2022 following PRISMA guidelines. Our pooled results showed a lower pregnancy rate among ANA-positive women undergoing IVF/ICSI compared to ANA-negative women undergoing the same procedures (279/908 versus 1136/2347, random effect, odds ratio -OR- 0.50, 95% confidence interval -CI- 0.38-0.67, p 0.00001, I 2 = 58%). We also reported a higher miscarriage rate among ANA-positive compared to ANA-negative women (48/223 versus 109/999, random effect, OR: 3.25 95% CI: 1.57-6.76, p = 0.002, I 2 = 61%) and a lower implantation rate (320/1489 versus 1437/4205, random effect, OR: 0.51, 95% CI: 0.36-0.72, p = 0.0001, I 2 = 78%). Regarding RPL, pooled results demonstrated a higher prevalence of ANA-positivity in RPL women compared to controls (698/2947 versus 240/3145, random effect, OR: 3.22, 95% CI: 2.12-4.88, p 0.00001, I 2 77%), either using > 2 or > 3 pregnancy losses threshold for defining RPL. Heterogeneity of reporting outcome did not allow a quantitative analysis and led to no clear demonstration of an effect of serum ANA on the incidence of stillbirth, preeclampsia and hypertensive disorders. In conclusion, the unfavorable effect of serum ANA was observed in women following IVF. Similarly, ANA were associated with the risk of RPL, while data were unconclusive in terms of late pregnancy complications., Competing Interests: Conflict of Interest All the authors have no financial and non-financial competing interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Septate uterus is the most common structural uterine anomaly, which is related to the adverse pregnancy outcomes in women of childbearing age. This article provides a retrospective review of hysteroscopic uterine septum resection performed in our hospital during recent years, focusing on the patients with recurrent miscarriage and primary infertility, and also to identify which patients are more likely to benefit from the surgery., Methods: This is a single-center retrospective study. Cases of women who underwent hysteroscopic septum resection at West China Second Hospital of Sichuan University from January 2014 to December 2019, retrieved through the medical record system, were divided into three groups: Group A was the recurrent miscarriage group, Group B had a history of pregnancy with spontaneous abortion once at most, and Group C was the primary infertility group. Each patient was followed up by telephone about further pregnancy, miscarriage and live birth for at least 1 year., Results: A total of 176 surgical patients were included in this study. Group A, B, and C include 42, 74, and 60 cases, respectively. The postoperative pregnancy rates of the three groups were 71.4, 82.4, and 75.0%; live births rates were 50.0, 74.3, and 71.7%; and spontaneous abortion rates were 21.4, 17.6, and 13.3%. 62 patients had a complete uterine septum and 114 had a partial uterine septum. For patients with complete septate uterus, the preoperative pregnancy rate was 54.84% and the pregnancy rate increased to 85.48% after surgery; and yet the preoperative and postoperative pregnancy rates in patients with partial septate uterus were close (from 71.9 to 72.8%)., Conclusions: After uterine septum resection, the pregnancy rate and spontaneous abortion rate in RSA patients were not significantly different from the other two groups, but the live birth rate was still significantly lower. Patients with complete uterine septum may benefit more from surgery. The surgical indications should be carefully and strictly evaluated., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We conducted a retrospective cohort study with the aim of investigating the relationship between subchorionic hematoma (SCH) and pregnancy outcomes in women with recurrent pregnancy loss (RPL). We reviewed all RPL patients who came to the Fourth Hospital of Shijiazhuang from January 2019 to June 2021. Two groups were divided according to the presence or absence of SCH. Live birth rate was considered as the primary outcome. Secondary outcomes included adverse pregnancy outcomes and complications. Univariable and multivariable analyses were conducted. Of 274 RPL women included in the final analysis, 49 (17.9%) had SCH. The occurrence of thrombophilia was significantly higher in SCH group than that in non-SCH group (38.8% vs 24.4%, P=0.041). There were no significant differences between the two groups in live birth rate, adverse pregnancy outcomes and pregnancy complications. Among women with SCH, live birth rate or SCH duration was not associated with continued use of low-dose aspirin (LDA) after the diagnosis of SCH. Our findings suggest that SCH does not reduce live birth rate in RPL women or increase the risk of adverse pregnancy outcomes or pregnancy complications. Continued use of LDA after the detection of a hematoma is unlikely to affect SCH duration or the live birth rate.