Predicting risk of subsequent pregnancy loss among women with recurrent pregnancy loss: An immunological factor-based multivariable model.

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.

Impact of recurrent pregnancy loss on depression, anxiety and fertility related stress in Omani women: A cross sectional survey.

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.

La grossesse est un état de bonheur et d'espoir non seulement pour une femme mais aussi pour sa famille ainsi que pour ses proches. Cependant, cette phase de bonheur s'effondre pour certains couples qui ne parviennent pas à mener à bien leur grossesse et finissent par perdre un bébé au début de la grossesse. Les fausses couches récurrentes (RPL) sont répandues chez les femmes omanaises et l'impact psychosocial de la RPL est lourd sur ces jeunes femmes, dévastant leur qualité de vie globale. Les chercheurs ont mené une enquête transversale auprès de 184 femmes omanaises ayant des antécédents de fausses couches récurrentes dans un hôpital universitaire de soins tertiaires pionnier. Collecte de données effectuée à l'aide d'un questionnaire autodéclaré pour évaluer la dépression, l'anxiété et le stress associé au RPL des femmes ayant des antécédents de RPL. L'âge moyen des femmes atteintes de RPL était de 34,05 ans et 81 % ont signalé 2 à 3 fausses couches. Les participants ont signalé des scores moyens plus élevés de dépression (9,94), d'anxiété (10,32) et de stress lié à la fertilité (30,28). Les femmes ayant subi plusieurs fausses couches (plus de 3) ont signalé un niveau d'anxiété plus élevé qui était significatif à (p<0.05%). Les résultats de l'étude actuelle ont également indiqué que les femmes atteintes de RPL connaissent des niveaux plus élevés de dépression, d'anxiété et de stress lié à la fertilité.

Preconception anti-annexin A5 antibodies are associated with subsequent live birth in women with recurrent miscarriage: A retrospective study from China.

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.

Adverse outcomes in subsequent pregnancies in women with history of recurrent spontaneous abortion: A meta-analysis.

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.

Future risk of metabolic syndrome after recurrent pregnancy loss: a cohort study using UK Biobank.

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.

Diagnostic workup of endocrine dysfunction in recurrent pregnancy loss: a cross-sectional study in Northeast China.

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.

Series of overviews on miscarriage and recurrent miscarriage.

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.

Superfertility and subfertility in patients with recurrent pregnancy loss: A comparative analysis of clinical characteristics and etiology based on differences in fertile ability.

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 ß2GPI 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.

We know all too well the significant psychological impact of miscarriage and recurrent miscarriage: so where is the support?

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.

The prevalence of sporadic and recurrent pregnancy loss.

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.

Obesity and recurrent miscarriage: The interconnections between adipose tissue and the immune system.

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.

Chronic endometritis: screening, treatment, and pregnancy outcomes in an academic fertility center.

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.

Chromosomal abnormalities in recurrent pregnancy loss and its association with clinical characteristics.

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.

The association of gut microbiome with recurrent pregnancy loss: A comprehensive review.

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.

'An extra level of kind of torment': Views and experiences of recurrent miscarriage care during the initial phases of COVID-19 in Ireland-A qualitative interview study.

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.

The Clinical Significance of Embryonic Chromosomal Errors in Recurrent Pregnancy Loss: an Analysis of 1107 Miscarriages.

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.

Platelet distribution width and the risk of unexplained recurrent pregnancy loss: a meta-analysis.

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; I2 =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; I2 = 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.

Adverse obstetric and perinatal outcomes of patients with history of recurrent miscarriage: a retrospective cohort study.

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.

Anti-Müllerian hormone and live birth in unexplained recurrent pregnancy loss.

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.

Cervicovaginal microbiome in patients with recurrent pregnancy loss.

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.