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Objectives To evaluate the agreement between multiplanar and Virtual Organ Computer-aided AnaLysis (VOCAL™) techniques for the measurement of total fetal thigh volume and to assess the repeatability and reproducibility of measurements performed using these methods; to derive birth weight-predicting models for both methods and to compare their accuracies. Methods This was a cross-sectional study of 150 singleton pregnancies at 30-42 weeks of gestation in which ultrasound volumes of the fetal thigh were obtained within 48 hours of delivery and measured using multiplanar and VOCAL techniques. Bland-Altman analyses were performed to determine the agreement between the two methods, and to evaluate intraobserver and interobserver variability in a subset of 40 patients. Birth weight-predicting models were derived using total fetal thigh volumes obtained using the VOCAL (ThiV) and multiplanar (ThiM) methods as independent variables. The accuracies of these formulas were compared. Results The mean percentage difference between measurements performed using the VOCAL technique and the multiplanar technique was −0.04 and the 95% limits of agreement were −8.17 and 8.09. The mean percentage difference and 95% limits of agreement between paired measurements in the assessment of intraobserver and interobserver variability were −1.10 (−7.67 to 5.47) and 0.61 (−7.68 to 8.91) for the VOCAL technique and 1.03 (−6.35 to 8.41) and −0.68 (−11.42 to 10.06) for the multiplanar method, respectively. The best-fit formulas for predicting birth weight (BW) were: BW = 1025.383 + 12.775× ThiV; and BW = 1033.286 + 12.733× ThiM. There was no significant difference between the accuracies of these formulas. Conclusions There is good agreement between the VOCAL and multiplanar techniques for assessment of total fetal thigh volume. Measurements performed using both methods are repeatable and reproducible. For prediction of birth weight, the formulas generated in this study can be used interchangeably. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sindrome de Down (SD) é uma alteração genética e metabólica complexa atribuída à presença de três cópias do cromossomo 21. O cromossomo extra em 93% dos casos é de origem materna e é resultante de uma segregação anormal durante a meiose (não-disjunção). Com exceção da idade materna avançada, fatores de risco para a não-disjunção meiótica não estão bem estabelecidos. Um estudo preliminar sugeriu que o metabolismo anormal do folato e a mutação 677 (C->T) no gene da metilenotetrahidrofolato redutase (MTHFR) podem ser fatores de risco maternos para a SD. A freqüência das mutações MTHFR 677 (C->T) e 1.298 (A->C) foram avaliadas em 36 mães de crianças com SD e em 200 indivíduos-controle. Os resultados demonstraram que as mutações 677 (C->T) e 1.298 (A->C) são mais prevalentes entre mães de crianças com SD do que nos controles. A heterozigose das duas mutações foi a combinação mais freqüente. O resultado desse estudo inicial sugere que mutações no gene da MTHFR seriam um fator de risco para a SD.

Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Immunotherapies have been a treatment proposed for recurrent miscarriages (RMs). The use of immunotherapies remains not recommended in the management of couples with RM. This overview of systematic reviews and meta-analysis (SRs-MAs) aims to identify and evaluate the quality of SRs-MAs that studied the effectiveness of immunotherapies in the treatment of RM patients. SRs-MAs were searched in PubMed/Medline, Embase, and Web of Science. SRs-MAs were analyzed using AMSTAR-2, PRISMA 2020, Risk of Bias in Systematic (ROBIS), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools to evaluate the methodological quality, reporting quality, risk of bias, and evidence quality of included SRs-MAs, respectively. This review included 20 SRs-MAs that evaluated the following immunotherapies: intravenous immunoglobulin (13 publications), lymphocyte immunotherapy (6 publications), corticosteroids (3 publications), and lipid emulsion (1 publication). SRs-MAs were rated as high methodological, moderate, and critically low quality in 14 (70 %), 1 (5 %), and 5 (25 %) SRs-MAs and high reporting, moderate, and low quality in 13 (65 %), 4 (20 %), and 3 (5 %) SRs-MAs, respectively. The overall risk of bias revealed a low risk of bias for three-quarters of the SRs-MAs. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis resulted in 23 outcomes, of which 4, 3, 5, and 11 results were of high, moderate, low, and very low quality, respectively. An improvement has been observed over the past few years in the quality of systematic reviews (SR)-MAs that have investigated the efficacy of intravenous immunoglobulin, lymphocyte immunotherapy, lipid emulsion therapy, and corticosteroids as a therapy for RM., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dysregulated natural killer (NK) cells have been associated with recurrent miscarriages (RM). Studies have suggested that high peripheral blood NK cell cytotoxicities (pNKCs) are associated with an increased risk of RM. The aim of this systematic review (SR) and meta-analysis (MAs) is to investigate the difference in pNKC between nonpregnant and pregnant women with RM and controls and determine whether pNKC is reduced by immunotherapy. We searched the PubMed/Medline, Embase, and Web of Science databases. The MAs were conducted to compare pNKCs between women with and without RM before and during pregnancy as well as pre- and post-immunotherapy. Risk of bias in nonrandomized studies was assessed by the Newcastle-Ottawa Scale. Statistical analysis was performed using the Review Manager software. A total of 19 studies were included in the SR and 14 studies in the MAs. The MAs revealed higher pNKCs among nonpregnant women with RM compared to controls (MD, 7.99 95 %CI 6.40-9.58; p < 0.00001). pNKCs were also higher in pregnant women with RM than in pregnant controls (MD, 8.21 95 %CI 6.08-10.34; p < 0.00001). Women with RM showed significantly decreased pNKCs after the immunotherapy compared to before (MD, -8.20 95 %CI -10.20 - -6.19; p < 0, 00001). Additionally, there is an association between high pNKCs and the risk of pregnancy loss in women with RM. However, included studies showed substantial heterogeneities regarding the inclusion criteria of patients, techniques measuring pNKC, and types of immunotherapies. More studies are needed to evaluate the clinical efficiency of pNKCs in managing RM., Competing Interests: Declaration of Competing Interest The authors have no relevant interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid ® 20%)., Methods: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma., Results: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET., Conclusion: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the first half of pregnancy and pregnancy loss is still unknown. Infections by other coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), appear to increase the risk of miscarriage. The purpose of this study is to assess whether SARS-CoV-2 infection increases the risk of miscarriage. Firstly, a narrative review of the literature on animal and human studies was performed to analyze the immunopathological mechanisms of SARS-CoV-2 infection during preconception and early pregnancy, by which it may increase the risk of miscarriage. Secondly, a systematic review/meta-analysis of studies was conducted to assess the prevalence of miscarriage in COVID-19 patients diagnosed during pregnancy. Meta-analysis of proportions was used to combine data, and pooled proportions were reported. Seventeen case series and observational studies and 10 prevalence meta-analyses were selected for the review. The estimate of the overall miscarriage rate in pregnant women with COVID-19 was 15.3 % (95 % CI 10.94-20.59) and 23.1 (95 % CI 13.17-34.95) using fixed and random effect models, respectively. Based on the data in the current literature, the miscarriage rate (<22 weeks gestation) in women with SARS-CoV-2 infection is in the range of normal population. Well-designed studies are urgently needed to determine whether SARS-CoV-2 infection increases the risk of miscarriage during periconception and early pregnancy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Problem: Lymphocyte immunotherapy (LIT) emerged in the early 1980s as a new therapeutic proposal for couples with a history of recurrent miscarriages (RM). However, in the early 2000s, the effectiveness of LIT was questioned. Recently, meta-analyses have observed the effectiveness and safety of LIT in treating couples with RM. Some studies evaluated the use of LIT in recurrent implantation failure (RIF) in in vitro fertilization cycles., Methods: This systematic and narrative review evaluated the data available in the literature regarding the efficacy and safety of the use of LIT. Searches in PubMed/Medline, Embase, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "recurrent implantation failure"., Results: This review describes the historical aspects of LIT and discusses its protocols, mechanisms of action, side effects, complications, and current evidence of the effectiveness in cases of reproductive failure. It also discusses the use of LIT during the COVID-19 pandemic and new immunological therapies., Conclusion: In the vast majority of studies, the use of LIT for RM couples has shown an improvement in pregnancy outcomes. The most of the current studies that support the evidence are quasi-experimental, with few randomized, double-blind studies (Level of evidence III). However, the current evidence are not convincing for the use of LIT in RIF patients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Altered immune and/or inflammatory response plays an important role in cases of recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). Exacerbation of the maternal immune response through increased NK cell activity and inflammatory cytokines can cause embryo rejection leading to abortion or embryo implantation failure. Immunosuppressors or immunomodulators can help or prevent this condition. Currently, lipid emulsion therapy (LET) has emerged as a treatment for RPL and RIF in women with abnormal NK cell activity, by decreasing the exacerbated immune response of the maternal uterus and providing a more receptive environment for the embryo. However, the mechanisms by which the intralipid acts to reduce NK cell activity are still unclear. In this review, we focus on the studies that conducted LET to treat patients with RPL and RIF with abnormal NK cell activity. We find that although some authors recommend LET as an effective intervention, more studies are necessary to confirm its effectiveness in restoring NK cell activity to normal levels and to comprehend the underlying mechanisms of the lipids action in ameliorating the maternal environment and improving the pregnancy rate., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Coronavirus disease 2019 (COVID-19) pandemic has spread rapidly across the world. The vast majority of patients with COVID-19 manifest mild to moderate symptoms but may progress to severe cases or even mortalities. Young adults of reproductive age are the most affected population by SARS-CoV-2 infection. However, there is no consensus yet if pregnancy contributes to the severity of COVID-19. Initial studies of pregnant women have found that COVID-19 significantly increases the risk of preterm birth, intrauterine growth restriction, and low birth weight, which have been associated with non-communicable diseases in offspring. Besides, maternal viral infections with or without vertical transmission have been allied with neurological and behavioral disorders of the offspring. In this review, obstetrical outcomes of women with COVID-19 and possible risks for their offspring are discussed by reviewing maternal immune responses to COVID-19 based on the current evidence. Structural and systemic follow-up of offspring who are exposed to SARS-CoV-2 in-utero is suggested., (Copyright © 2020 Elsevier B.V. All rights reserved.)

COVID-19 pandemic is affecting various areas of health care, including human reproduction. Many women with reproductive failures, during the peri-implantation period and pregnancy, are on the immunotherapy using immune modulators and immunosuppressant due to underlying autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. Many questions have been raised for women with immunotherapy during the COVID-19 pandemic, including infection susceptibility, how to manage women with an increased risk of and active COVID-19 infection. SARS-CoV-2 is a novel virus, and not enough information exists. Yet, we aim to review the data from previous coronavirus outbreaks and current COVID-19 and provide interim guidelines for immunotherapy in women with reproductive failures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: "recurrent implantation failure," "intrauterine infusion," "Platelet-Rich Plasma (PRP)," "Peripheral Blood Mononuclear Cells (PBMC)," "Granulocyte Colony-Stimulating Factor (G-CSF)," and "Human Chorionic Gonadotropin (hCG)." The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G-CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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; I 2  = 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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the difference between chromosomal abnormalities between the gender of couples affected by Recurrent miscarriage (RM) and if there is an association between previous obstetric history and chromosomal abnormalities of the parents. Methods: Multicenter, retrospective, observational study from seven different RM clinics between 2006 and 2016. We enrolled 707 couples (1014 participants) with a history of RM. We compared the frequency of chromosomal abnormalities between groups of couples with primary and secondary RM and separated between women and their partners. Furthermore, we compared the prevalence of chromosomal abnormalities between groups based on the number of previous spontaneous abortions. Results: The overall prevalence of all cytogenetic abnormalities was 5.59% ( n  = 1414, women and their partners). Excluding cases of polymorphism and inversion of chromosome 9, which are considered variants of normality, the prevalence in all individuals was 2.26% ( n  = 32/1414). The comparative analysis of cases of chromosomal abnormalities among couples with primary and secondary RM based on the number of previous miscarriages (PM) revealed a similar frequency between groups. The statistical analysis of the total cases (primary PM + secondary PM) in these three groups were as follows: (a) couple, 2 pm versus 3 pm vs. ≥4 PM, p  = .514; (b) women, 2 pm versus 3 pm vs. ≥4 PM, p  = .347; and (3) partner, 2 pm versus 3 pm vs. ≥4 PM, p  = .959. Chromosomal abnormalities were significantly more prevalent among women than among their partners (6.9 versus 4.2%; p  = .027). Moreover, the distribution of leading chromosomal abnormalities among women was different compared with their partners. Among women, we observed these abnormalities in the following frequency order: mosaicism (38.8%), polymorphism (32.6%), translocation (16.3%), and inversion (12.3%). Among their partners, these abnormalities were polymorphism (73.3%), inversion (13.3%), mosaicism (6.7%), and translocation (6.7%). Conclusion: The number of PM and the history of full-term pregnancy does not correlate with an increase or decrease in the prevalence of cytogenetic abnormalities in couples with RM.

Introduction Pregnant women with polycystic ovarian syndrome (PCOS) have high risk of pregnancy loss. Pathophysiological mechanisms appear to be associated with obesity, hormonal factors, or blood clotting disorders. Our aim is to perform a systematic review and meta-analysis on the relationship between coagulation disorders and risk of recurrent miscarriage (RM) in patients with PCOS and to identify coagulation biomarkers for this condition. Material and Methods PubMed and MEDLINE databases were searched for publications in English language. The search terms used included "RM", "polycystic ovary syndrome", "coagulation disorders", and "thrombophilia". Odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage in different RM groups (with and without PCOS). Results A total of 575 publications including the search terms were identified. Six studies were included for qualitative analysis, and five were included for quantitative analysis (meta-analysis). We found no association between RM and inherited thrombophilias in patients with PCOS: (1) Factor V Leiden (OR, 0.74; 95% CI, 0.38 - 1.45; p = 0.38); (2) C677T methylenetetrahydrofolate reductase polymorphism (MTHFR) (OR, 1.01; 95% CI, 0.64 - 1.59; p = 0.97); and (3) A1297C MTHFR polymorphism (OR, 1.08; 95% CI, 0.62 - 1.89; p = 0.77). Other potential biomarkers were identified, with emphasis on plasminogen activator inhibitor type 1. Conclusion Data available in the current literature revealed that there was no association between RM and inherited thrombophilias in patients with PCOS. RM patients with PCOS have a high risk of thromboembolic events.

Objective: This study aims to elucidate which types of recurrent miscarriage (RM) patients experienced a livebirth after paternal lymphocyte immunotherapy (LIT) and to evaluate the perinatal outcome., Study Design: Retrospective analysis of a multicenter, observational study which enrolled 1096 couples with a history of two or more spontaneous miscarriages without any intercalated delivery. We conducted an intention-to-treat analysis of couples with RM treated with or without LIT regarding to gestational and perinatal outcomes. We compared groups by using the Student's t -test or Kruskal-Wallis test, Fisher's exac t -test and χ 2 test when appropriate., Results: The success of gestation was significantly higher in the LIT group (60.1% vs. 33.1%; p  <  0.001). A sub-analysis of four different immune disorder groups revealed a significantly higher success in the LIT group in all immune categories, except in patients who had autoantibodies positive. We observed no significant differences in perinatal outcomes such as gestational age at birth, preterm and extreme preterm birth, and birth weight in successful pregnancy in both groups. The success rate was significantly higher when LIT was administrated before and during pregnancy and only during pregnancy compared to only before pregnancy ( p  <  0.01)., Conclusions: Careful laboratory test phenotyping of RM patients may identify subgroups most likely to benefit and exclude those with little likelihood of benefit, and LIT during a pregnancy may significantly improve success rates.

Screening of fetomaternal hemorrhage (FMH) is essential in management of fetomaternal antigen incompatibilities of blood. The objective in this study was to evaluate the ability of automatic blood analyzer (ABA) to screen FMH, also comparing this method with flow cytometry (FCM). The contents of fetal red blood cells and fetal hemoglobin were evaluated by FCM and ABA, respectively, using both blood samples of male adults laced with umbilical cord blood diluted at 1/10, 1/100, 1/1,000, and 1/10,000, or blood from puerperal women collected within 48 hours following delivery. FCM had better performance (area under curve, AUC = 0.8723) than ABA (AUC = 0.6569) in detecting fetal blood laced with blood from male adults. At a critical level of 0.5%, ABA indicated that 27.5% of puerperal women would have FMH while FCM did not detect FMH. Our results showed that ABA overestimates FMH and disagrees with FCM on indicating puerperal women with FMH. ABA is inadequate for being used to screen for or to measure FMH.

The aim of this study is to perform a systematic review and meta-analysis on the relationship between excess weight and risk of recurrent pregnancy loss (RPL) and to highlight the common immunological mechanisms of these two conditions. The PubMed and MEDLINE databases were searched for publications in English available as of November 2017. The search terms used were 'recurrent pregnancy loss', 'body mass index' (BMI), 'overweight' and 'obesity'. For calculation of the odds ratio (OR) and 95% confidence intervals (CI) for miscarriage in different BMI groups, RevMan software was used (Review Manager, Version 5.3.5 for Windows; The Cochrane Collaboration). In total, 100 publications including the search terms were identified. Six studies were included for qualitative analysis, and two studies were included for quantitative analysis (meta-analysis). The association between excess weight and RPL was significant (OR, 1.34; 95% CI, 1.05-1.70; P = 0.02). The isolated analyses of the groups of obese and overweight women revealed an association only between obesity and RPL (OR, 1.75; 95% CI, 1.24-2.47; P = 0.001). The data available in the current literature revealed that obese women with a history of RPL have a high risk of future pregnancy losses, a risk which was not found among overweight women., (© 2018 Japan Society of Obstetrics and Gynecology.)

Problem: To evaluate the predictors of successful pregnancies in women with a history of recurrent miscarriages (RMs) having undergone lymphocyte immunotherapy (LIT)., Method of Study: Retrospective, multicenter, observational study which involved 702 pregnant women with history of RM treated with LIT. Comparative analysis of women with a history of RM having undergone LIT and experienced treatment success vs those having experienced treatment failure along with the analysis of the association between the number of prior miscarriages and the efficacy of LIT., Results: A total of 421 women were able to carry the pregnancy to term, with treatment success rate of 60%. The multivariate analysis showed that age, the association between autoantibodies and thrombophilia, and the number of previous miscarriages were factors associated with LIT failure. Secondary RMs alone were not found to be a factor predictive of LIT success or failure; however, secondary RMs among women with a history of 5 or more RM were found to be a predictor of LIT success (OR: 10.24; 95% CI: 1.9-55.8; P = .007)., Conclusion: Age, the number of previous miscarriages, and the association between autoantibodies and thrombophilia are associated with LIT failure. A higher number of previous miscarriages in cases of secondary RM resulted in better LIT outcomes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction  The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective  To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods  This case-control study included 130 infertile women consulting at a private clinic between March 2003 and March 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis  The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results  The frequency of the mutation was of 58.5% for the case group ( n  = 76) and of 49.2% for the fertile controls ( n  = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions  These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when the mutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility., Competing Interests: Conflict of Interests: Authors declare no conflict of interest., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Purpose: Recurrent miscarriage (RM) affects up to 2-3% of couples of reproductive age. There are several causes for this condition, including immunologic. The embryo is considered an allograft, subject to the rejection mechanisms of the maternal immune system. Immunotherapy involving immunization with lymphocytes is considered in cases of idiopathic RM. However, there is still no consensus regarding the efficacy and safety of this therapy., Methods: This systematic review and meta-analysis evaluated the data available in the literature regarding the efficacy and safety of the use of immunotherapy with lymphocytes in couples with history of RM. Searches in PubMed/Medline, SCOPUS, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "meta-analysis." Statistical analyses were performed using Review Manager 5.3 (RevMan), version 5.3., Results: Six published meta-analysis were retrieved; two found no improvements in the rate of live births after the use of immunization with lymphocytes in the treatment of RM, and four found a beneficial effect of the use of immunotherapy with lymphocytes in cases of RM, with significant improvements in the rate of live births., Conclusion: Data available in the literature supports the efficacy and safety of immunotherapy with lymphocytes in cases of RM without an identified cause.

Objective: To assess the perinatal outcomes and risk factors for further pregnancy loss in patients with recurrent miscarriage treated with lymphocyte immunotherapy (LIT)., Methods: We performed a retrospective observational study of women with a history of two or more consecutive miscarriages who underwent LIT. All patients had undergone investigation of the etiology of the pregnancy losses according to a specific protocol. These etiologic factors were compared between those whose pregnancy outcome was successful and those who had a further miscarriage. The comparison between the groups was performed by Kruskal-Wallis, Fisher exact and Chi-square tests. Perinatal outcome data were collected for the successful pregnancies., Results: One-hundred six patients were included. The mean number (±SD) of previous pregnancies, deliveries and miscarriages in all patients were 2.73 ± 0.8, 0.19 ± 0.4 and 2.54 ± 0.6, respectively. A successful pregnancy outcome after lymphocyte therapy occurred in 82 patients (group I), while 24 (22.6%) sustained a further miscarriage (group II). There was no statistical difference in the genetic, anatomic and hormonal causes of miscarriage between the groups (p > 0.05). Antinuclear (ANA) and antithyroglobulin (TgAb) autoantibodies occurred more frequently in group II (p = 0.0010 and p = 0.0024, respectively). Of those with successful pregnancies, 11 women (13.4%) had a preterm delivery. The mean birth weight was 3036.4 ± 498.6 g., Conclusion: In patients with recurrent miscarriage treated with LIT, the presence of ANA and TgAb was a risk factor for further pregnancy loss. Perinatal outcomes in those whose pregnancies continued were favorable.