自然流产（spontaneous abortion，SA）是妇产科最常见的妊娠并发症之一。育龄期女性发生1次SA的风险为10%左右［1］。复发性流产（recurrent spontaneous abortion，RSA）的发生率为1%～5%［2］，RSA的复发风险随着流产次数的增加而上升。曾有3次以上连续自然流产史的患者再次妊娠后胚胎丢失率为40%～80%［3］。如果不及时干预，不仅会给患者及其家庭带来严重的经济负担，而且还将对患者的身心健康造成极大的影响。浏览更多请关注本刊微信公众号及当期杂志。

Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.Copyright © 2021 Elsevier Ltd. All rights reserved.

Many human conceptions are genetically abnormal and end in miscarriage, which is the commonest complication of pregnancy. Recurrent miscarriage, the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive. It is associated with psychological morbidity, and has often proven to be frustrating for both patient and clinician. A third of women attending specialist clinics are clinically depressed, and one in five have levels of anxiety that are similar to those in psychiatric outpatient populations. Many conventional beliefs about the cause and treatment of women with recurrent miscarriage have not withstood scrutiny, but progress has been made. Research has emphasised the importance of recurrent miscarriage in the range of reproductive failure linking subfertility and late pregnancy complications and has allowed us to reject practice based on anecdotal evidence in favour of evidence-based management.

Approximately one-fourth of pregnant women will experience bleeding in the first trimester. The differential diagnosis includes threatened abortion, early pregnancy loss, and ectopic pregnancy. Pain and heavy bleeding are associated with an increased risk of early pregnancy loss. Treatment of threatened abortion is expectant management. Bed rest does not improve outcomes, and there is insufficient evidence supporting the use of progestins. Trends in quantitative ß subunit of human chorionic gonadotropin (ß-hCG) levels provide useful information when distinguishing normal from abnormal early pregnancy. The discriminatory level (1,500 to 3,000 mIU per mL) is the ß-hCG level above which an intrauterine pregnancy should be visible on transvaginal ultrasonography. Failure to detect an intrauterine pregnancy, combined with ß-hCG levels higher than the discriminatory level, should raise concern for early pregnancy loss or ectopic pregnancy. Ultrasound findings diagnostic of early pregnancy loss include a mean gestational sac diameter of 25 mm or greater with no embryo and no fetal cardiac activity when the crown-rump length is 7 mm or more. Treatment options for early pregnancy loss include expectant management, medical management with mifepristone and misoprostol, or uterine aspiration. The incidence of ectopic pregnancy is 1% to 2% in the United States and accounts for 6% of all maternal deaths. Established criteria should be used to determine treatment options for ectopic pregnancy, including expectant management, medical management with methotrexate, or surgical intervention.

        早期妊娠稽留流产（missed early miscarriage）是指妊娠≤12周，胚胎或胎儿已死亡并滞留在子宫腔内，未能及时自然排出。流产发生时，虽然胚胎已经停止发育，但是胎盘滋养层细胞可以继续释放绒毛膜促性腺激素等激素，胚胎及组织物未排出，孕妇有或无流血、腹痛等临床症状，妇科检查时宫颈口未开。早期妊娠稽留流产常常在超声检查时被发现。浏览更多请关注本刊微信公众号及当期杂志。

To determine whether the frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss (REPL).Observational cohort study using prospectively collected data.Academic RPL program.A total of 372 women with REPL, defined as ≥2 pregnancy losses<10 weeks, and at least one ultrasound-documented miscarriage with chromosome results.Body mass index (BMI) was measured at the initial consultation and at each subsequent pregnancy. Conventional cytogenetic analysis and, when indicated, microsatellite analysis and/or comparative genomic hybridization was performed.Frequency of euploid miscarriage in obese (BMI≥30 kg/m2) and nonobese (BMI<30 kg/m2) subjects, before and subsequent to REPL evaluation.There were 578 miscarriages with chromosome results. Of the subjects, 18% were obese at the time of miscarriage. The mean maternal age at miscarriage was similar between the obese and nonobese groups. Due to the high rate of maternal cell contamination in the prior miscarriages, only subsequent miscarriages with chromosome results were included in the primary analysis. Of the 117 subsequent miscarriages, the frequency of an euploid miscarriage among obese women was 58% compared with 37% of nonobese women (relative risk=1.63; 95% confidence interval 1.08-2.47).Obese women with REPL have an increased frequency of euploid miscarriage, which is a known risk factor for subsequent miscarriage.Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extra-embryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extra-embryonic mesoderm rather than chorionic villi. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.

Aneuploidy in the conceptus or fetus, occurs in 5-10% of all pregnancies and is a common reproductive problem in humans. Most aneuploid conceptuses die in utero, resulting in early pregnancy loss. Causes of recurrent miscarriage may include abnormal chromosomes in either partner, particularly translocations, antiphospholipid antibodies and uterine anomalies. Chromosomal aberrations in parents are a major pre-disposing factor and causative of abortion if carried over to the embryo. The transmission rate in the embryo can be speculated to be about 50%. Embryo morphology, developmental rates, and maternal age are correlated with chromosomal abnormalities. Translocation in either partner is one of the most important causes of recurrent miscarriage and the prognosis of subsequent pregnancy in couples with abnormal embryonic karyotype is poorer than that in couples with normal chromosome karyotypes. As for parents whose karyotypes are normal, the frequency of normal embryonic karyotypes significantly increases with the number of previous abortions and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage. Recently, many kinds of genetic polymorphisms have also been found to be associated with recurrent miscarriages. In contrast, preimplantation genetic diagnosis for aneuploidy screening is sometimes performed in patients with unexplained recurrent miscarriages. We review genetic factors as a cause of miscarriage.

While chromosomal abnormalities are often the cause of missed abortions, other defects could be involved, which might be screened for by transcervical embryoscopy.A total of 272 patients with missed abortion underwent transcervical embryoscopy prior to dilatation and curettage, together with cytogenetic analysis of chorionic villi, using either standard G-banding cytogenetic techniques or comparative genomic hybridization in combination with flow cytometry analysis.Visualization of the embryo or early fetus (12 cases) was successful in 233 patients, and karyotyping in 221. Among 233 examined cases, 33 had normal external features, 71 were classified as growth-disorganized and 129 had either isolated or multiple defects, including holoprosencephaly, anencephaly, encephalocele, spina bifida, microcephaly, facial dysplasia, limb reduction defect, cleft hand, syndactyly, pseudosyndactly, polydactyly, various forms of cleft lip and an amniotic adhesion. Of the 165 cases with an abnormal karyotype, there were 46 grossly disorganized embryos, 98 multiple defects, six single defects and 15 morphologically normal cases. Of the 56 cases with a normal karyotype, there were 20 grossly disorganized embryos, 16 multiple defects, four single defects and 16 morphologically normal cases.A total of 75% of the cases with missed abortion had an abnormal karyotype, 18% had a morphological defect with a normal karyotype, while no embryonic or chromosomal abnormality could be diagnosed in 7% of the cases. Correlation of morphological and cytogenetic findings in spontaneous abortion specimens could provide valuable information for genetic counselling and prenatal care in future pregnancies in couples with a history of repeated pregnancy loss.

Chromosome abnormalities account for half of the recorded miscarriages. Data from cytogenetic analysis of the products of conception (POC) in miscarriages are reviewed in the paper. Genetic analysis of POC allows patients to be given prognostic information. Molecular genetic techniques can overcome the pitfalls of conventional karyotyping, such as culture failure and trace submicroscopic abnormalities. We compare the pros and cons when these technologies are applied to the analysis of POC after miscarriage. Guidance is also provided for future clinical applications. The objective of the review is to help clinicians understand the limitations and to optimise the usefulness of genetic analysis of POC.

Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persistent antiphospholipid antibodies (aPL). Although researchers have made progress in characterizing different clinical phenotypes of aPL-positive people, the current approach to clinical management is still mostly based on a 'one size fits all' strategy, which is derived from the results of a limited number of prospective, controlled studies. With the 2023 publication of the ACR-EULAR APS classification criteria, it is now possible to rethink APS, to lay the groundwork for subphenotyping through novel pathophysiology-informed approaches, and to set a future APS research agenda guided by unmet needs in clinical management.© 2024. Springer Nature Limited.

Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease.Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin antibodies and anti-beta 2-glycoprotein 1 antibodies. APS can present with a variety of clinical phenotypes, including thrombosis in the veins, arteries and microvasculature as well as obstetrical complications. The pathophysiological hallmark is thrombosis, but other factors such as complement activation might be important. Prevention of thrombotic manifestations associated with APS includes lifestyle changes and, in individuals at high risk, low-dose aspirin. Prevention and treatment of thrombotic events are dependent mainly on the use of vitamin K antagonists. Immunosuppression and anticomplement therapy have been used anecdotally but have not been adequately tested. Pregnancy morbidity includes unexplained recurrent early miscarriage, fetal death and late obstetrical manifestation such as pre-eclampsia, premature birth or fetal growth restriction associated with placental insufficiency. Current treatment to prevent obstetrical morbidity is based on low-dose aspirin and/or low-molecular- weight heparin and has improved pregnancy outcomes to achieve successful live birth in > 70% of pregnancies. Although hydroxychloroquine and pravastatin might further improve pregnancy outcomes, prospective clinical trials are required to confirm these findings.

To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard.The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%.These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Antiphospholipid syndrome (APS) is an autoimmune condition that is associated with thrombosis and morbidity in pregnancy. The exact mechanisms by which these associations occur appear to be heterogeneous and are not yet well understood. The aim of this study was to identify and analyze publications in recent years to better understand the diagnosis and its contribution to monitoring APS among women with recurrent miscarriage (RM). This systematic review and meta-analysis was conducted using the PubMed and Web of Knowledge databases, with articles published between 2010 and 2014, according to the PRISMA statement. Of the 85 identified studies, nine were selected. Most of the studies reported an association between recurrent miscarriage and specific antiphospholipid antibodies, as anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2-glycoprotein I antibodies (aβ2GPI) and antiphosphatidylserine (aPS), which showed a relationship with RM. The main result of the meta-analysis revealed association between antiphospholipid antibodies (aPLs) and/or APS compared to the patients with RM (OR: 0.279; 95% CI: 0.212-0.366) and APS cases compared to the patients with RM (OR: 0.083; 95% CI: 0.036-0.189). High heterogeneity among these studies (I=100.0%, p <0.001) was observed. In addition, there was no significant publication bias across studies according to Begg's test (p=0.230), although Egger's test (p=0.037) suggests significant publication bias. The funnel plot was slightly asymmetrical. Systematic review and meta-analysis demonstrated a positive association between antiphospholipid antibodies and/or antiphospholipid syndrome in patients with recurrent miscarriage.Copyright © 2017 Elsevier B.V. All rights reserved.

Antiphospholipid syndrome (APS) is a rare heterogenous autoimmune disorder with severe life-threatening complications shown during pregnancy. In this analysis, we aimed to systematically compare the pregnancy outcomes (both maternal and fetal) in patients with APS.

New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.

To compare the clinical characteristics and pregnancy outcomes between patients with primary obstetric antiphospholipid syndrome (OAPS) and those with primary non‐criteria obstetric antiphospholipid syndrome (NC‐OAPS), and to identify the risk factors of adverse pregnancy outcomes in both groups.

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.© 2020 International Society on Thrombosis and Haemostasis.

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85–19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07–25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77–24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine.

Assessment of the prevalence of anti‐phosphatidylserine‐prothrombin antibodies (aPS/PT) with OAPS and SN‐OAPS in Chinese patients.

To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects.The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Studies have investigated the relationship between antinuclear antibodies (ANA) and recurrent miscarriage (RM). The objective of this paper is to evaluate the presence of ANA as a risk factor for spontaneous abortion in patients with RM. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta‐Analysis, the authors performed systematic review and meta‐analysis by searching the databases of PubMed/Medline and SCOPUS. Review Manager, Version 5.3 performed the statistical analysis. Binary variables were analyzed by odds ratio (ORs) and 95% confidence interval (CI). The subgroup analysis compared the effect of different ANA titers. The authors analyzed the ANA patterns of immunofluorescence staining. Seven case‐control studies were selected. The frequency of positive ANA was statistically higher in the RM group (20.6%, 288/1400) as compared to the control group (6.7%, 72/1080). The meta‐analysis of the positive ANA showed a statistical difference between the two groups (OR 3.30, 95% CI 1.41‐7.73; I2 = 87%, P = .006). Studies have revealed different frequencies of ANA patterns of immunofluorescence. This meta‐analysis suggested that positive ANA might increase the risk of RM. However, it was not possible to conclude which ANA pattern of immunofluorescence staining is more frequent in the RM group.

Antinuclear antibodies (ANAs) are valuable laboratory markers to screen for and support the diagnosis of various rheumatic diseases (known as ANA-associated rheumatic diseases). The importance of ANA testing has been reinforced by the inclusion of ANA positivity as an entry criterion in the 2019 systemic lupus erythematosus classification criteria. In addition, specific ANAs (such as antibodies to Sm, double-stranded DNA (dsDNA), SSA/Ro60, U1RNP, topoisomerase I, centromere protein B (CENPB), RNA polymerase III and Jo1) are included in classification criteria for other rheumatic diseases. A number of techniques are available for detecting antibodies to a selection of clinically relevant antigens (such as indirect immunofluorescence and solid phase assays). In this Review, we discuss the advantages and limitations of these techniques, as well as the clinical relevance of the differences between the techniques, to provide guidance in understanding and interpreting ANA test results. Such understanding not only necessitates insight into the sensitivity and specificity of each assay, but also into the importance of the disease context and antibody level. We also highlight the value of titre-specific information (such as likelihood ratios).

The relationship between anti-SSA/RO antibodies and pregnancy has been reported previously, and we aim to visualize the rates of maternal and infant outcomes with anti-SSA/RO.

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Reproductive failures include infertility and recurrent pregnancy loss (RPL). Although the relative importance of immunological factors in human reproduction remains unclear, there may be immune‐mediated reproductive failures in a portion of unexplained infertility and RPL. As a cause of immunological factor, anti‐sperm antibodies (ASA) are produced both in men and women. There have been reported several antigens in the surface of sperm that are especially foreign to women. The presence of ASA, especially sperm‐immobilizing antibodies, in the sera of infertile women has been shown to inhibit sperm migration in the female genital tract. Therefore, the effectiveness of the treatments for infertile women with sperm‐immobilizing antibodies by timed intercourse or intra‐uterine insemination is limited. Such antibodies can also exert inhibitory effects on various stages of sperm‐egg interaction and subsequent embryo development in vitro. It is suggested that ASA testing for infertile women should be performed before proceeding IVF. The manipulation of gametes and embryos from patients having sperm‐immobilizing antibodies should be carefully carried out especially to avoid contaminating patient's serum and follicular fluid in the culture medium in order to overcome the immunological causes of female infertility by ASA, and satisfactory results under suitable conditions for gametes and embryos have been obtained. The relationship between ASA and RPL was controversially reported. Increased miscarriage rates in women with ASA were demonstrated by some authors. In contrast, lack of association between ASA and RPL was reported. In this manuscript, we are focusing the roles of ASA in women with reproductive failures.

Pregnancy stimulates an elaborate assortment of dynamic changes, allowing intimate approximation of genetically discordant maternal and fetal tissues. Although the cellular and molecular details about how this works remain largely undefined, important clues arise from evaluating how a prior pregnancy influences the outcome of a future pregnancy. The risk of complications is consistently increased when complications occurred in a prior pregnancy. Reciprocally, a prior successful pregnancy protects against complications in a future pregnancy. Here, we summarize immunological perturbations associated with fetal loss, with particular focus on how both harmful and protective adaptations may persist in mothers. Immunological aberrancy as a root cause of pregnancy complications is also considered, given their shared overlapping risk factors and the sustained requirement for averting maternal-fetal conflict throughout pregnancy. Understanding pregnancy-induced immunological changes may expose not only new therapeutic strategies for improving pregnancy outcomes but also new facets of how immune tolerance works that may be applicable to other physiological and pathological contexts.

To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect.Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, prepregnancy blood samples from 31 RSA women and 10 controls were obtained.We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment.Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.

\n\n\nThe clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no ‘gold standard’ test to define deficiency.

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before the 20th week of gestation with the same partner. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were reported to have an effect on embryonic development and pregnancy success. To clarify the effects of MTHFR polymorphisms on the risk of RPL in the Chinese population, a meta-analysis was performed.Related studies were identified from Medline, Embase, Web of Science, and Chinese Databases up to March 7th, 2015. We extracted the number of both C677T and A1298C genotypes in the cases and controls. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to estimate the associations. Data analysis was performed using Stata 13.1.Sixteen articles involving 1420 RPL cases and 1408 controls were included in this meta-analysis. MTHFR C677T polymorphism was significantly associated with RPL risk under dominant (TT + CT vs. CC; OR 2.10, 95 % CI 1.76-2.50), recessive (TT vs. CC + CT; OR 2.36, 95 % CI 1.92-2.90), heterozygote (CT vs. CC; OR 1.77, 95 % CI 1.32-2.37), homozygote (TT vs. CC; OR 3.55, 95 % CI 2.76-4.56), and additive (T vs. C; OR 1.83, 95 % CI 1.64-2.05) model. Sensitivity analyses excluding studies that deviated from HWE did not change the direction of effect. For the A1298C mutation, no significant association was found. The Egger's regression asymmetry test showed no significant publication bias.Identification of MTHFR C677T mutation would have some implication for primary prevention of RPL and screening of high-risk individuals in China. Large well-designed researches are needed to fully describe the associations.

To determine the diagnostic importance of platelet aggregation studies, we evaluated the clinical utility of these assays by a retrospective review of 188 adult patients initially studied for bleeding abnormalities with platelet aggregation tests at a tertiary care hospital from 1984 to 1987. The primary indications for requesting the tests in our patient population were for the evaluation of a positive bleeding history or abnormal bleeding time (68%), hypercoagulability (17%), thrombocytosis (9%), or a family history of a bleeding disorder (6%). There was a statistically higher incidence of platelet aggregation test abnormalities in patients with highly abnormal bleeding times (40%), in patients with thrombocytosis from myeloproliferative disorders (65%), and in patients with a family history of a bleeding disorder (58%), compared to the other groups studied (16-29%). Of the 64 platelet aggregation tests performed that were abnormal, the following abnormalities were identified: 19 aspirin-like defects (poor response to arachidonate and decreased second wave responses to weak agonists), which were presumably drug-induced, ten myeloproliferative-type disorder defects (abnormal response to epinephrine predominantly) in patients known to have myeloproliferative disease, 34 abnormal patterns not characterized as aspirin or myeloproliferative disorder related, four of which ultimately led to a diagnosis of storage pool disease, and one spontaneous aggregation defect. Our results suggest that platelet aggregation tests rarely lead to the diagnosis of a specific, previously undiagnosed platelet function disorder. Specific recommendations are given for efficient utilization of platelet aggregation tests.

Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. Deep venous thrombosis and pulmonary embolism are the most common manifestations, but thrombosis in unusual locations also occurs. The current evidence suggests that the mutation has at most a modest effect on recurrence risk after initial treatment of a first venous thromboembolism. Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. The clinical expression of Factor V Leiden is influenced by the number of Factor V Leiden alleles, coexisting genetic and acquired thrombophilic disorders, and circumstantial risk factors. Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein. The first acute thrombosis is treated according to standard guidelines. Decisions regarding the optimal duration of anticoagulation are based on an individualized assessment of the risks for venous thromboembolism recurrence and anticoagulant-related bleeding. In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic Factor V Leiden heterozygotes, although prophylactic anticoagulation may be considered in high-risk clinical settings. In the absence of evidence that early diagnosis reduces morbidity or mortality, decisions regarding testing at-risk family members should be made on an individual basis.

Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)?

The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery.Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used 'optimal' and 'suboptimal' tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations.We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5-8.5] in the unselected population, 8.0% (95% CI, 5.3-12) in infertile women, 13.3% (95% CI, 8.9-20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3-32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1-7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations.Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.

To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction.Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed.A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively).Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

To systematically review studies reporting the risk of spontaneous abortion among pregnant women of typical reproductive potential with and without uterine leiomyomas.We searched PubMed, EMBASE, Web of Science, and ClinicalTrials.gov for publications from January 1970 to December 2016.We excluded studies that did not use imaging to uniformly document leiomyoma status of all participants, did not have a comparison group without leiomyomas, or primarily included women seeking care for recurrent miscarriage, infertility care, or assisted reproductive technologies.Two authors independently reviewed eligibility, extracted data, and assigned overall quality ratings based on predetermined criteria. Of 1,469 articles identified, nine were eligible. Five enrolled general obstetric populations and four included women undergoing amniocentesis. In five studies in general obstetric populations that included 21,829 pregnancies (1,394 women with leiomyomas and 20,435 without), only one adjusted for potential confounders. This meta-analysis revealed no increase in risk of spontaneous abortion among those with leiomyomas compared with those without (11.5% compared with 8.0%; risk ratio 1.16, 95% CI 0.80-1.52). When bias from confounding was estimated for nonadjusted studies, the aggregate calculated risk ratio was 0.83 (95% CI 0.68-0.98).Leiomyoma presence was not associated with increased risk of spontaneous abortion in an analysis of more than 20,000 pregnant women. Failure of prior studies to adjust for confounders may have led to the common clinical belief that leiomyomas are a risk factor for spontaneous abortion.

Hysteroscopic adhesiolysis anatomically restores the uterine cavity in cases of Asherman's syndrome (AS); however, the extent of endometrial fibrosis could determine the pregnancy outcome.To determine whether endometrial thickness could influence pregnancy outcome of hysteroscopic adhesiolysis in women with a history of AS.This was a retrospective cohort study that included 41 women who attended Women's Specialized Hospital, King Fahad Medical City from December 2008 to December 2015, presented with a history of infertility or recurrent pregnancy loss, and were diagnosed with intrauterine adhesions and treated by hysteroscopic adhesiolysis. To analyze the causative factors of AS, history of curettage, miscarriage, postpartum hemorrhage, hysteroscopy, endometritis, and any uterine surgery were recorded. Patients were followed up for 2 years to account for pregnancy. Patients were divided into two groups based on measurement of endometrial thickness in the midsagittal plane at mid-cycle of a menstrual period. Group A consisted of 26 patients with endometrial thickness ≤5 mm, and group B included 15 patients with endometrial thickness >5 mm. The main outcome measures included endometrial thickness and pregnancy outcome.Group A had significantly (<0.001) lower pregnancy rates compared with group B (38.4% versus 80%, respectively). Five of 10 pregnancies (50%) from group A miscarried, compared with 1 of 12 (8.3%) pregnancies in group B. This was statistically significant (<0.001).Pregnancy rates were observed to be higher when the endometrium was >5 mm in thickness among patients with AS and miscarriage rates may be reduced in this group.

To evaluate differences in Doppler parameters and pregnancy outcomes, if any, and to determine the predictive accuracy of such indices, as well as the effects of low-dose aspirin (LDA) in unexplained recurrent pregnancy loss (URPL).An observational study was conducted at Ren Ji Hospital, Shanghai, China, from May 2015 to December 2016. The endometrial thickness, and the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) values of endometrial and uterine artery blood flow were collected. Receiver operating characteristic (ROC) curve analysis was used to analyze data from URPL patients (three or more first-trimester spontaneous abortions with unknown etiology) and patients with normal fertility. A second ultrasonography examination was performed in URPL patients who had received daily LDA for 2 months.There were 190 URPL patients and 35 control patients. Endometrial thickness was significantly thinner in URPL patients than control patients (P=0.005). The PI, RI, and S/D values for endometrial blood flow and the mean PI, RI, and S/D values for uterine arteries were significantly higher in URPL patients (P<0.001). The predictive accuracy of the indices mentioned above were 0.660, 0.802, 0.852, 0.837, 0.784, 0.929, and 0.929, respectively. Following LDA supplementation, URPL patients showed a significant reduction in resistance to endometrial and uterine artery blood flow (P<0.001).URPL patients had impaired uterine perfusion. Doppler parameters are valuable in predicting women at high risk of URPL. LDA could be effective in improving endometrial receptivity.© 2020 International Federation of Gynecology and Obstetrics.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is associated with recurrent miscarriage. Despite the many studies that have investigated the prevalence of PCOS in recurrent miscarriage, the extent to which PCOS contributes remains highly uncertain. The majority of these studies have used the polycystic ovary morphology alone to define PCOS and the results are extremely variable due to a variety of diagnostic and selection criteria used. Only a very small number of studies have investigated the prevalence of hyperandrogenaemia in recurrent miscarriage. Most crucially, to the authors' knowledge, there is not yet a single publication which has investigated the true prevalence of the complete syndrome of PCOS in recurrent miscarriage using the Rotterdam criteria. Hence there is an urgent need to reappraise the prevalence of PCOS in recurrent miscarriage using the Rotterdam criteria. The possible mechanisms by which PCOS could cause recurrent miscarriage are considered: hyperandrogenaemia, obesity and hyperinsulinaemia are the most likely candidates, although further work is clearly needed. This paper also reviews the possible treatment options for women diagnosed with recurrent miscarriage associated with PCOS. There is some evidence to suggest that weight loss, ovarian drilling and metformin could help to reduce the rate of miscarriage.

To determine the incidence of an abnormal glucose tolerance test in patients with recurrent spontaneous abortion and whether metformin would safely reduce the rate of first trimester spontaneous abortions in patients without polycystic ovary syndrome (PCOS) as well as with PCOS and an abnormal glucose tolerance test.Prospective control clinical trial.Shiraz University-affiliated hospital.Patients with a history of recurrent spontaneous abortion and women with a history of normal full term pregnancy.The incidence of abnormal carbohydrate metabolism was determined. Metformin and placebo were given to women with an abnormal glucose tolerance test and who had recurrent spontaneous abortions.Continuation of pregnancy beyond the first trimester in all groups and presence or absence of teratogenicity in the delivered baby after metformin therapy.Twenty-nine of the patients in the group with recurrent spontaneous abortion were found to have an abnormal glucose tolerance test result compared with just four (5.4%) patients in the normal pregnancy group. The abortion rate was significantly reduced after metformin therapy in patients without PCOS in comparison to the placebo group (15% vs. 55%).This study indicates an important link between an abnormal glucose tolerance test and a history of recurrent abortion. It was also found that metformin therapy improves the chances of a successful pregnancy in patients with an abnormal glucose tolerance test.

The role of prolactin in early pregnancy is controversial. The aim of this study was to evaluate the relationship between serum prolactin concentration and the risk of miscarriage in women with unexplained recurrent miscarriage (RM). A series of 174 women with unexplained RM, who had serum prolactin concentrations measured from January 2000 to September 2009 at the Recurrent Miscarriage Clinic in Royal Hallamshire Hospital in Sheffield, were included in this study. Among the 174 patients with unexplained RM, 40 patients did not conceive during the study period, 9 were lost to follow-up and 125 patients conceived again. Patients who did not conceive were significantly older than those who conceived (p < 0.05, OR: 1.08, 95% CI: 1.03-1.13). Among those who conceived again, the pregnancy outcome data were available for analysis in 109 patients. Those who miscarried were older (p < 0.05, OR: 1.1, 95% CI: 1.01-1.22) and had significantly lower serum prolactin concentrations (p < 0.05, adjusted OR: 0.99, 95% CI: 0.97-0.99) after adjustment has been made for age, than those who had a live birth. Lower basal serum prolactin concentrations were associated with an increased risk of miscarriage in a subsequent pregnancy in women with unexplained RM.

To study whether diminished ovarian reserve is associated with recurrent miscarriage.Cross-sectional clinical study.Tertiary-care center.Women with history of recurrent miscarriage (RM; n = 71) and sequentially selected age-matched fertile women who were seeking contraception (control; n = 70).Not applicable.Serum levels of FSH, LH, E2, and antimüllerian hormone (AMH); FSH/LH ratio; ovarian volumes; and antral follicle count (AFC).The levels of FSH were 8.6 ± 3.7 U/L in the RM group and 7.1 ± 3.9 U/L in the control group; this difference was statistically significant. The levels of AMH were significantly lower in the RM group than in the control group (2.9 ± 1.7 ng/mL vs. 3.6 ± 1.7 ng/mL). The percentage of women with levels of FSH ≥11 U/L was significantly higher in the RM group than in the control group (18.3% vs. 4.3%). In the RM group, the percentage of women with levels of AMH ≤1 ng/mL was significantly higher than in the control group (19.7% vs. 5.7%).Recurrent miscarriage may be associated with diminished ovarian reserve. Larger prospective randomized controlled trials are warranted to better determine the predictive potential of ovarian reserve markers in recurrent miscarriage.Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The effects of maternal subclinical hypothyroidism on pregnancy outcomes are not clear.

The prevalence of polycystic ovaries (PCO) was established amongst 2199 consecutive women (median age 33 years; range 19-46) with a history of recurrent miscarriage (median 3; 3-14). A diagnosis of PCO was made if the ovarian volume was enlarged (>9 ml), there were >/=10 cysts of 2-8 mm in diameter in one plane and there was increased density of the stroma. In a cohort study, the prospective pregnancy outcome of 486 of the women scanned who were antiphospholipid antibody negative and who received no pharmacological treatment during their next pregnancy was studied. The prevalence of PCO was 40.7% (895/2199). The livebirth rate was similar amongst women with PCO (60.9%; 142/233) compared to that amongst women with normal ovarian morphology (58.5%; 148/253; not significant). Neither an elevated serum luteinizing hormone concentration (>10 IU/l) nor an elevated serum testosterone concentration (>3 nmol/l) was associated with an increased miscarriage rate. Polycystic ovarian morphology is not predictive of pregnancy loss amongst ovulatory women with recurrent miscarriage conceiving spontaneously. The search for a specific endocrine abnormality that can divide women with PCO into those with a good and those with a poorer prognosis for a future successful pregnancy continues.

This review aimed to investigate the association of insulin resistance (IR) in women with recurrent pregnancy loss compared to women with normal pregnancy history.

To investigate the differences in insulin resistance between women with recurrent miscarriage and those with normal pregnancy.Pregnant women with a history of recurrent miscarriage were included in the patient group (n = 97), while those with no history of abnormal pregnancy were included in the control group (n = 52). Both groups consented to undertake an oral glucose tolerance test and insulin-releasing test between the 5th and 13th weeks of pregnancy.(1) Levels of fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, and homeostasis model assessment β function were not statistically significantly different (p < 0.05) between the two groups. (2) The area under the curve of glucose and area under the curve of insulin were higher in the patient group than in the control group. The composite insulin sensitivity index of the patient group was lower than that of the control group. The differences in these three parameters between the groups were statistically significant (p < 0.05).Women with a history of recurrent miscarriage are at an increased risk for insulin resistance during the first trimester of a new pregnancy.Copyright © 2011 S. Karger AG, Basel.

Background: Previous studies have described the association between dysbiosis of the vaginal microbiota (VMB) and related dysbiotic conditions, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), and various adverse pregnancy outcomes. There is limited overview of this association from countries in sub-Saharan Africa (SSA), which bear a disproportionally high burden of both vaginal dysbiotic conditions and adverse pregnancy outcomes. This systematic review assesses the evidence on the association between VMB dysbiosis, BV, and AV, and late adverse pregnancy outcomes in women living in SSA.

Recurrent pregnancy loss (RPL), defined as two or more failed clinical pregnancies, affects 1%–3% of couples trying to conceive. Nowadays up to 50% of cases remain idiopathic. In this context, paternal factors evaluation is still very limited. The aim is to address the topic of the male factor in RPL with a broad approach, analyzing collectively data on sperm DNA fragmentation (SDF) and semen parameters. We systematically searched in Pubmed/MEDLINE and Google Scholar from inception to February 2023. A protocol has been registered on PROSPERO (ID number CRD42022278616). PRISMA guidelines were followed.

Could the risk of subsequent pregnancy loss be predicted based on the risk factors of recurrent pregnancy loss (RPL) patients?