Idiopathic Recurrent Miscarriage Research Articles

Attenuated Total Reflectance–Fourier Transform Infrared (ATR-FTIR) Spectroscopy Combined With Deep Learning for Classification of Idiopathic Recurrent Spontaneous Miscarriage (IRSM)

Idiopathic recurrent spontaneous miscarriage (IRSM) is characterized by the repeated losses of two or more clinically detected pregnancies before 24 week of gestation with the cause remaining unknown. We aim to ascertain whether attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy with deep learning (DL) can accurately distinguish IRSM from controls. Endometrial tissue (internal lining of the uterine cavity) was collected from 20 women with IRSM and 20 controls during window of implantation. ATR-FTIR spectroscopy was used to acquire spectra (400–4000 cm−1) from three random locations across each specimen and averaged. Multivariate analysis was used to assess group differentiation. Furthermore, DL classifiers were implemented to predict IRSM. Hierarchical cluster analysis (HCA) demonstrated distinct clustering of the two groups. The principal component analysis (PCA) loading plot indicated contributions from amide I, II and III bands, symmetric methyl (CH3) bending of proteins, lipids, nucleic acids, asymmetric stretching of CH2 due to lipids, collagen, and glucose in discriminating between IRSM and controls. Supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) exhibited optimized discrimination between the groups. Convolutional neural network (CNN) and variational autoencoder-artificial neural network (VAE-ANN) classifiers exhibited good performance and showed classification accuracy of 94% and 94% and F1 scores (mean of recall and precision) of 95% and 93%, respectively. The optimal area under the receiver operating characteristic curve (AUC) value of both CNN and VAE-ANN was 0.94. ATR-FTIR spectroscopy combined with DL approach is promising for understanding complex disease pathophysiology and enabling early prediction.

Особенности микробиоты кишечника у женщин с идиопатическим привычным выкидышем

Currently, researchers show considerable interest in the link between gut microbiota and idiopathic recurrent miscarriage (IRM). This study aimed to analyze taxonomic changes of gut microbiota and assess its relationship with plasma levels of cortisol, melatonin, TNFa and IL17 in women with IRM. We invited 55 women with IRM and 60 women with normal pregnancy, studied their gut microbiota, and registered serum concentrations of cortisol, melatonin, TNFa and IL17. Women with IRM had changed gut microbiota: significantly decreased — diversity (Chao1 p = 0.014), significantly decreased abundance of Bifidobacterium (p < 0.001), Lachnospira (p = 0.032), Roseburia (p = 0.003), Coprococcus (p = 0.012), and significantly increased abundance of Ruminococcus (p < 0.001) and Klebsiella (p = 0.002). We have shown a statistically significant relationship between cortisol level and abundance of Lachnospira (r = –0.51; p = 0.002), melatonin level and abundance of Coprococcus (r = –0.49; p = 0.012), and identified connections between TNF and IL17 concentrations and Chao1 index (r = –0.51; p = 0.002, r = –0.54; p = 0.001, respectively), TNF concentration and abundance of Ruminococcus (r = 0.51; p = 0.002), IL17 concentration and abundance of Bifidobacterium (r = –0.52; p = 0.001). Modulation of gut microbiota may have preventive and therapeutic effects in women with IRM.

Genes of Inflammation and Placental Function GWAS Associated with Idiopathic Recurrent Miscarriage in the Kazakh Population.

The loss of two or more pregnancies is considered recurrent miscarriage (RM). One of the causes of this pathology is the occurrence of mutations both in pleiotropic and pathway-specific regulators and in structural genes. The simplest type of such mutations is single nucleotide polymorphisms. The aim of the study is to study the relationship between gene polymorphisms of anti- and pro-inflammatory cytokines - interferon-gamma (T874A), interleukin (IL1B) (C3954T), IL6 (G572C) and IL10 (G1082A); placental function, apoptosis and angiogenesis - apolipoprotein C-III (APOC3) (G5163C), kinase insert domain receptor (A1719T, G1192A), P53 (Arg72Pro) and signal transducer and activator of transcription 3 (STAT3) (C1697G) with the development of idiopathic RM (iRM) in the Kazakh population. This was a case-control study. Molecular genetic studies were performed by TaqMan using a single site-specific amplification and real-time genotyping method in 302 women with iRM and 300 with normal reproduction. DNA isolation from the biomaterial was carried out using kits containing binding magnetic particles. Both samples were analysed for alleles and genotypes for the studied polymorphisms. For statistical data processing, Pearson's criterion, confidence interval (CI) and probability value were taken into account. It was found that the carriage of unfavourable genotypes (G/C, C/C) for the G5163C polymorphism of the APOC3 gene increases the risk of developing iRM by three times (odds ratio = 3.0; 95% CI = 2.24-4.07). Other studied polymorphisms in the genes of ILs, interferon, P53 proapoptotic protein, kinase domain receptor and STAT3 transcription activator were not associated with RM. Significant associations of APOC3 gene genotypes with the development of iRM in the Kazakh population indicate the involvement of the placental system, which is realised by vascularisation defects and defective embryo implantation and leads to early pregnancy termination.

Association of Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.

The clustered homeobox gene family known as the Hox family plays a fundamental role in the morphogenesis of the vertebrate's embryo. A long noncoding RNA (lncRNA), known as HOTTIP (HOXA transcript at the distal tip), has been functionally characterized and contributed to the pathogenesis of various conditions. The current case-control study was undertaken to examine the gene frequencies and shared alleles of the HOTTIP gene in Iranian participants with or without idiopathic recurrent spontaneous abortion (RSA). Both ARMS-PCR reaction and RFLP-PCR techniques were employed to detect three HOTTIP polymorphisms (rs2023843C/T, rs78248039A/T, and rs1859168C/A) in a DNA sample of 161 women with RSA and 177 healthy women. We found that the TT genotype of the HOTTIP rs2023843 C/T polymorphism was associated with a lower risk for idiopathic RSA. In contrast, the TT genotype of the HOTTIP rs78248039 A/T polymorphism was correlated with an enhanced risk of RSA. The presence of the A-allele for HOTTIP rs1859168 C/A polymorphism was associated with an increased risk for idiopathic RSA. Haplotype analysis showed that the T/T/A, C/T/A, T/T/C, and T/A/A haplotypes of rs2023843/rs78248039/rs1859168 enhanced RSA susceptibility. Computational analysis predicted that this lncRNA might act as a potential sponge for some microRNAs; therefore, affecting the expression of genes being targeted by them. In addition, both rs2023843 and rs1859168 variants could alter the local secondary structure of HOTTIP. Our results showed that HOTTIP rs2023843C/T, rs78248039A/T, and rs1859168C/A polymorphisms may confer genetic susceptibility to idiopathic RSA in an Iranian population.

The sequence variation of mitochondrial tRNA tyrosine and cysteine among Iranian women with idiopathic recurrent miscarriage: A case-control study.

Recurrent miscarriage is one of the most prevalent reproductive diseases. This phenomenon has several reasons, including maternal, hormonal, immunological, and parental genetic factors. Idiopathic recurrent miscarriage (IRM), with no distinctive etiology, involves about half of the recurrent miscarriage cases. Some mutations in mitochondrial DNA can lead to miscarriage. Mitochondrial tRNA (mt-tRNA) mutations cause nearly half of the mitochondrial disorders. To identify mt- tRNA gene mutations in Iranian women with IRM. In this case-control study, 100 Iranian women with IRM and 100 women as control without any history of miscarriage were investigated by polymerase chain reaction-single strand conformation polymorphism technique followed by gene sequencing. Bioinformatics analysis were done using human mitochondrial genome database, molecular evolutionary genetics analysis, mammalian mitochondrial-tRNA, etc. Results showed 4 mt-tRNA mutations including 1 cysteine mt-tRNA mutation (5824CT) and 3 tyrosine mt-tRNA mutations (5868TA, 5849CT, and 5836TC) in our cases. Amongst the 4 mutations found, one was novel that is still not reported. Our bioinformatics analysis revealed that these mutations can be pathogenic. They occurred in tRNA-conserved regions and their secondary structure was changed, which can result in mitochondrial dysfunction. Mutations of these genes may help in the assessment of IRM. Further study of all 22 mt-tRNAs possible mutations is recommended to describe their etiologic role in IRM.

Editorial Expression of Concern: Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study.

Editorial Expression of Concern: Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study.

Impact of heavy metal pollution on idiopathic recurrent spontaneous abortion

Impact of heavy metal pollution on idiopathic recurrent spontaneous abortion

Progestagens in high-risk pregnancy. What we know today

Miscarriage remains an important global problem: 23 million miscarriages are registered annually in the world, i.e. 44 pregnancy losses every minute, and the total risk of miscarriage is 15.3% of all pregnancies. Effective methods of pregnancy preservation (in case of idiopathic miscarriage and threatened miscarriage) include lifestyle modification and progestagen therapy. Progesterone is the main hormone necessary to maintain pregnancy.The effectiveness of progestogens among medical methods that increase the chances of pregnancy preservation has been proven by numerous studies. Effectiveness and safety of various types of progestogens during pregnancy have been studied. As a result, progesterone and dydrogesterone became the only progestogens approved for use in obstetrics – micronized progesterone and dydrogesterone reduce the frequency of miscarriage in women with clinical diagnoses of threatened miscarriage and idiopathic recurrent miscarriage. In addition, the progestogens safety has been carefully studied in modern randomized studies, prospective trials and meta-analyses and the same safety profile of dydrogesterone and micronized progesterone for pregnant women and the fetus has been proven.Studies have shown that oral dydrogesterone has relatively low antagonistic activity at glucocorticoid and mineralocorticoid receptors compared to progesterone and therefore well tolerated. Oral dydrogesterone due to the peculiarities of structure has improved bioavailability compared to progesterone, which allows a woman to avoid the inconvenience and discomfort associated with the intravaginal or intramuscular use of progesterone. In addition, dydrogesterone has a 1.5 times higher affinity for progesterone receptors compared to micronized progesterone and a pronounced anti-inflammatory and immunomodulation effect, which provides certain clinical advantages for patients after recurrent pregnancy losses.Thus, progestogens are indicated for all patients with recurrent pregnancy losses from the moment of receiving a positive pregnancy test, as they reduce the risk of miscarriage. It is important that the use of progestagen drugs during the first and second trimester of pregnancy is not associated with side effects

Role of the HLA-G regulatory region polymorphisms in idiopathic recurrent spontaneous abortions (RSA).

HLA-G polymorphisms have a functional impact on its expression and may cause a breakdown of maternal tolerance towards the semi-allogenic fetus, resulting in recurrent spontaneous abortions (RSA). This study reports on the association of HLA-G regulatory region polymorphisms with idiopathic RSA. Seventy-five couples with ≥2 spontaneous abortions were recruited in comparison to 75 healthy couples who had normal pregnancies. About 5mL of blood samples were collected from all the participants, and DNA was extracted. Screening of HLA-G 5'-upstream regulatory region (5'-URR) was done by direct sequencing in 50 each of RSA and healthy couples, respectively. The 14bp deletion/insertion polymorphism in the 3'-untranslated region (3'-UTR) was genotyped in 75 each of RSA and healthy couples, respectively, by PCR amplification of HLA-G exon 8. MedCalc, GraphPad Prism, Haploview, PLINK, and multifactor dimensionality reduction were used to analyze the data. HLA-G screening revealed the presence of -762C/T, -725C/G, -716T/G, -689A/G, -486C/A, and -477C/G single nucleotide polymorphisms (SNPs) in the 5'-URR. At positions -762 and -477, the frequency of CC homozygotes was significantly higher in controls compared to the patients. The 14bp deletion/insertion polymorphism in the 3'-UTR showed an association with RSA with the heterozygous genotype being significantly higher in RSA compared to controls. The study indicates a protective role of the CC genotypes of the two HLA-G 5'-URR polymorphisms, -762C/T and -477C/G, against RSA. It also suggests that women with the 14bp deletion/insertion genotype have a significantly higher risk of RSA.

P-504 Pregnancy outcome of intravenous immunoglobulin in women with recurrent pregnancy loss

Abstract Study question Does intravenous immunoglobulin(IVIG) increase live births in recurrent miscarriage(RM) women with cellular immune abnormality such as high NK cell level and cytotoxicity and TNF-α/IL-10 ratio? Summary answer IVIG treatment increased the live birth rate of RM women with abnormal cellular immunity. What is known already Various causes of RM have been identified but even with a detailed evaluation, almost half of the cases have unidentified etiologies. Immune imbalance is one of the proposed potential etiologies of these idiopathic RM. To regulate abnormal cellular immunity, treatment such as IVIG is proposed to improve pregnancy outcomes. However, the use of IVIG in RM is still controversial. In addition, one of the widely used indicators of immune imbalance in pregnancy is the NK cell level, but there is a disagreement in setting the cut-off value. The percentage varies from 12 to 18%. Study design, size, duration RM was defined as women with two or more spontaneous abortions and in total, 987 RM women visited Department of Obstetrics and Gynaecology, Konyang University Hospital(KYUH) from January 2007 to December 2020. Only those with a full evaluation and known treatment outcome were included. A total 204 idiopathic RM and 209 RM women with known aetiology were enrolled. Participants/materials, setting, methods We investigated the pregnancy outcome by sorting the patients into seven subgroups depending on abnormal cellular immunity including NK cell level, NK cell cytotoxicity and TNF-α/IL-10 ratio. Then, to verify the cut-off value(16.1%) of NK cell level which we set in our previous study, patients were classified into three groups according to their NK cell level: 1) <12%(low), 2) 12-16%(moderate), 3) >16%(high). Main results and the role of chance Among all RM women with at least one abnormal cellular immunity were treated with IVIG and the overall live birth rate (LBR) was 80.2%. The group which did not have IVIG treatment showed an overall LBR of 78.0%. Within the 7 groups with abnormal cellular immunity, the group with both high NK cell toxicity and TNF-α/IL-10 ratio showed the highest LBR, 100% of LBR and the group with both high NK cell level and TNF-α/IL-10 ratio showed the lowest treatment outcome, 71.4%. To verify the adequacy of our cut-off value, after excluding those with high NK cell cytotoxicity and TNF-α/IL-10 ratio, 152 patients were classified into low, moderate, and high level of NK cells. LBR were 81.0%, 72.5%, and 76.9%. Limitations, reasons for caution The study was designed retrospectively, resulting in numerous follow-up losses. It is a single-centered study that may not be enough to generalize the diagnosis method and treatments from these findings. Moreover, IVIG is an expensive drug that may lead to certain patient preferences. Wider implications of the findings The study may provide evidence in selecting RM patients with immune abnormalities to be treated with IVIG and raise their pregnancy outcomes. We can also apply these results to the reproductive failure group. A detailed evaluation and an evidence-based treatment are important. Trial registration number not applicable

Uterine Natural Killer Cells in the Context of Implantation: Immunohistochemical Analysis of Endometrial Samples from Women with Habitual Abortion and Recurrent Implantation Failure

Infertility affects approximately 48 million couples globally. Despite the enormous progress of the methods of reproductive medicine that has been made since the first test-tube baby was born in 1978, the implantation rate of day-3 embryos is only around 15-20 % and 30 % of day-5 embryos. Numerous strategies aim to improve implantation rates and prevent repeated implantation failure, however there is no specific general recommendation leading to satisfying results. One of the many risk factors relevant in this regard is the uterine immunological make-up, mainly the uterine Natural Killer (uNK) cells. They orchestrate the overall immune response during implantation by influencing trophoblast invasion and vascular remodeling and throughout pregnancy, uNK cells are also the main immune cells at the maternal-foetal interface. Previously, uNK count has been correlated with various fertility issues including idiopathic reccurent miscarriage. The present study used endometrial samples collected from 256 patients with recurrent implantation failure (RIF), habitual abortion (HA) and idiopathic sterility. Samples were collected between day 19 and 21 of the menstrual cycle mainly by Pipelle endometrial sampling. The samples were fixed in formalin for 24 hours and further processed for immunohistochemistry using anti-CD56 to visualize this antigen marker of uNK cells. Immunohistochemical counting was performed to assess the low, normal, or elevated count of uNK cells. According to the one-way ANOVA test, the age of our patients did not have any influence on the count of uNK cells. With Spearman correlation analysis, we found statistically significant correlation (p-value 0.05) of -0.133 between prior miscarriage and lower uNK cell count. Using the same analysis we found statistically significant correlation (correlation 0.233 with p-value 0.01) between number of uNK cells and activation status. Patients with higher uNK cells were more frequenty diagnosed with endometriosis (p-value 0.05, correlation 0.130). Patients with an immunological factor of sterility (defined by a clinical immunologist) had a lower chance of gravidity (-0.203 with p-value 0.01). Based on our results, we can confirm that there is a correlation between RIF, HA, idiopathic sterility, endometriosis, and immunological factor of sterility (uNK cell count). The true predictive value with regard to fertility outcomes needs to be addressed in future research.

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/050, May 2022).

Purpose The aim of this guideline is to standardize the diagnosis and therapy of recurrent miscarriage (RM) using evidence from the recent literature. This is done by using consistent definitions, objective evaluations and standardized treatment protocols. Methods When this guideline was compiled, special consideration was given to previous recommendations in prior versions of this guideline and the recommendations of the European Society of Human Reproduction and Embryology, the Royal College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine, and a detailed individual search of the literature about the different topics was carried out. Recommendations Recommendations about the diagnostic and therapeutic procedures offered to couples with RM were developed based on the international literature. Special attention was paid to known risk factors such as chromosomal, anatomical, endocrinological, physiological coagulation, psychological, infectious and immune disorders. Recommendations were also developed for those cases where investigations are unable to find any abnormality (idiopathic RM).

Identification of a Novel Protein Interactions that Elucidates the Mechanism of Hydatidiform Molar Pregnancies in Women with NLRP2 and NLRP7 Mutations

Abstract Mutations in NLRP2 and NLRP7 genes result in genetic maternal imprinting disorders. These genes have been identified to be maternal effect genes regulating early embryo development in idiopathic recurrent miscarriage. Previous research suggests that NLRP2 and NLRP7 regulate DNA methylation and immune signaling through inflammasome formation. However, the exact mechanisms underlying recurrent miscarriages are not known. In this study, we report a novel protein interaction of Human proliferation-associated 2G4 (PA2G4, aka: EBP1) with NLRP2 and NLRP7 through an unbiased yeast 2-hybrid screen of a human HeLa cell cDNA library. Protein interactions were confirmed by co-immunoprecipitation and confocal microscopy. Furthermore, global DNA methylation decreased in cells that overexpressed NLRP2/7 and EBP1. Our results further support the role for NLRP2/7 in regulating DNA methylation as a mechanism for recurrent miscarriages. Since EBP1 is implicated in apoptosis, cell proliferation, and differentiation, our discovery significantly advances our understanding of NLR biology and helps to explain the cellular pathways involved in idiopathic recurrent miscarriages. Supported by grants from Beta Beta Beta Biological Honor Society

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study.

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0.029) and allelic C vs. T (OR = 0.028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2.81 for rs2961920) and codominant GG vs. AA (OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta-analysis.

Reports said immunotherapy is effective for the treatment of idiopathic recurrent miscarriage (RM). Immunotherapy is invasive, and lymphocyte therapy carries some risk of infection. Oral immunosuppressants have the advantages of simple administration and convenience; however, there is no statistical analysis of whether they can improve pregnancy outcomes in patients with idiopathic RM. Six databases were searched for studies on oral immunosuppressants and RM; 374 articles were identified. There were two oral immunosuppressants, cyclosporine A and prednisone; two studies were on cyclosporine A and three studies were on prednisone for RM. In total, 554 RM patients were included in this analysis, including 357 patients who received oral immunosuppressive agents and 197 patients who received basic treatment, placebo, or no treatment. Oral administration of cyclosporine A or prednisolone increases live birth rate (OR=3.6, 95% CI: 2.1-6.15, p<0.00001) and ongoing pregnancy rate (OR=8.82, 95% CI: 2.91-26.75, p=0.0001) in patients with idiopathic RM. Drug use reduced miscarriage rate (OR=0.21, 95% CI: 0.08-0.52, p=0.0007); however, there was significant heterogeneity (I2 =73%) and a moderate-to-severe risk of bias. There was no effect on premature birth rate (OR=2.26, 95% CI: 0.96-5.31, p=0.06). This meta-analysis cannot provide a reference for the duration of medication treatment because the selected studies had inconsistent durations. We did a statistical analysis and found that oral immunosuppressants (including cyclosporine A or prednisolone) can improve pregnancy outcomes in patients with idiopathic RM, increase live birth rate and ongoing pregnancy rate, and reduce miscarriage rate.

Copy number variations as a risk factor for couples with idiopathic recurrent miscarriage: A systematic review

Copy number variations as a risk factor for couples with idiopathic recurrent miscarriage: A systematic review

Genetic Factors of Idiopathic Recurrent Miscarriage in Kazakh Population.

Background:It seems that 50% of the possible causes of recurrent miscarriage do not have any explainable etiology and they require in-depth etiopathogenesis analysis. The purpose of this research was to study polymorphisms relationship of the immune response genes including Val249Ile CX3CR1 (rs3732379), CT60 G/A CTLA4 (rs3087243), and HLA DQA1, DQB1, DRB1 (major histocompatibility complex, class II) with development of idiopathic form of recurrent miscarriage (iRM) in Kazakh population.Methods:TagMan genotyping for 302 patients with iRM and 300 women with normal reproduction was performed. Molecular genetic studies were carried out by the TaqMan method of unified site-specific amplification and real-time genotyping using test systems. Statistical tests and Chi Square were carried out using PLINK, STATA13 software and p<0.05 was considered statistically significant.Results:It has been shown that carriage of unfavorable genotypes (Val/Ile, Val/Val) by the Val249Ile polymorphism of CX3CR1 gene increases the risk of developing iRM by 1.43 times. Search for associations of genes allelic variants of HLA class 2 complex with iRM revealed 501 allele in DQA1 locus, 0301 in DQB1 locus, 10, 12, 15, 16 alleles in DRB1 locus, which increase the risk of developing iRM in Kazakh population.Conclusion:The highly significant associations of immune response genes with development of iRM in Kazakh population indicate the possible involvement of the immune system interaction of mother cells with syncytiotrophoblast, which is realized by vascular defects and defective embryo implantation, causing termination of pregnancy.

Expression of Concern.

International Journal of Gynecology & ObstetricsEarly View EXPRESSION OF CONCERNFree Access Expression of Concern This article corrects the following: Randomized controlled study of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion related to antiphospholipid syndrome Alaa M. Ismail, Ali H. Hamed, Srdjan Saso, Ahmad M. Abu-Elhasan, Mona M. Abu-Elghar, Aymen N. Abdelmeged, Volume 132Issue 2International Journal of Gynecology & Obstetrics pages: 219-223 First Published online: December 2, 2015 First published: 27 November 2021 https://doi.org/10.1002/ijgo.14039AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Ismail AM, Hamed AH, Saso S, Abu-Elhasan AM, Abu-Elghar MM, Abdelmeged AN. Randomized controlled study of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion related to antiphospholipid syndrome. Int J Gynaecol Obstet. 2016 Feb;132(2):219–23. 10.1016/j.ijgo.2015.09.004. This Expression of Concern is for the above article, published online on 2 December 2015 in Wiley Online Library (wileyonlinelibrary.com) and has been published by agreement between the journal Editor-in-Chief, Prof Michael Geary, and John Wiley & Sons Limited. The journal was made aware of concerns regarding the integrity of the data underlying this research and identical observations between this article and two others.1, 2 The authors and Assiut University responded to the concerns raised and Assiut University conducted a full review of the raw data, randomization process, study design and authorship. Assiut University found that the data correlates with the results and any similarities with other studies is mostly due to chance. However, the authors were unable to fully address concerns regarding randomization of the data, inclusion criteria and discrepancies between the trial registration record and the reported outcomes. Given this, the journal has concerns regarding the integrity of the research and has decided to issue this Expression of Concern. REFERENCES 1Fawzy M, Shokeir T, El-Tatongy M, Warda O, El-Refaiey AA, Mosbah A. Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study. Arch Gynecol Obstet. 2008; 278(1): 33- 38. CrossrefCASPubMedWeb of Science®Google Scholar 2Ismail AM, Abbas AM, Ali MK, Amin AF. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. J Maternal-Fetal Neonatal Med. 2017; 31(1): 388- 394. PubMedGoogle Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Macrophage inhibiting factor in women with habitual miscarriage in pregnancy following immunocytotherapy

The aim of our study was to evaluate the macrophage inhibitory factor (MIF) content of in peripheral blood serum, as well as MIF production by mitogen-stimulated cells from whole peripheral blood during pregnancy in women with idiopathic recurrent miscarriage who received immunocytotherapy both prior to and in the first trimester of pregnancy. The study involved 51 women 20 to 40 years old: 10 fertile healthy females beyond pregnancy, 23 women with idiopathic recurrent miscarriage (IRM), 18 women with a physiological course of pregnancy at different stages of gestation (12, in the first trimester; 12, in the second; 9, in third trimester). MIF content was assessed by multiplex analysis using flow fluorometry. Of 23 women with IRM, six lost their pregnancy in the first trimester, 14 women prolonged pregnancy to the full-term resulting into birth of a healthy child; three had premature births at 24 to 35 weeks with a live fetus. There were no intergroup differences in the serum MIF level in control women and in patients with IRM, both beyond and during pregnancy. However, the dynamics of this index during pregnancy, was similar with increase during the II and III trimesters in both groups of women (control and with IRM). During pregnancy, the dynamics of MIF production by mitogen-activated cells from peripheral blood was also similar, except for values in the II trimester: in this period, MIF production in women with IRM was significantly lower, although it was still increased 3 times compared to the 1st trimester (5-fold to controls). In women with physiological pregnancy, the serum MIF levels at 5 to 6 weeks were lower than in women in both IRM subgroups, but there was no difference in MIF content for women with miscarriage and full-term pregnancy. Similarly, there were no differences of MIF contents in the supernates of activated whole blood cells of women at the time of study within groups and between the groups at the same time of examination. It has been shown that ICT has a positive effect on the course and outcomes of pregnancy in women with pregnancy prolonged to full-term. The serum MIF content in women with full-term pregnancy is higher than in women with miscarriage, which is consistent with results of other authors about adverse developmental effects of low serum MIF levels at early pregnancy terms. The results obtained indicate that immunocytotherapy do not regularly promote pregnancy to full term in women with IPV. Therefore, further research is required to find out criteria for administering ICT in treatment of idiopathic recurrent miscarriage.

Immunogenetic aspects of idiopathic recurrent miscarriage in the Kazakh population.

There are numerous scientific studies of recurrent miscarriage (RM) with possible causes, such as fetal chromosomal abnormalities, infectious agents, adverse environmental factors, bad habits, anatomical defects, thrombophilic disorders, etc. However, RM causes in 50% of cases remain unknown. These RM cases do not have any explainable etiology, and they require in-depth etiopathogenesis study, thus they are considered idiopathic RM. The purpose of this research is to study polymorphisms relationship of the immune response genes CX3CR1 (rs3732379, Val249Ile), CTLA4 (rs3087243, CT60 G/A), and HLA DQA1, DQB1, DRB1 (major histocompatibility complex, class II) with the idiopathic form of recurrent miscarriage (iRM) development in Kazakh population. Independent replicative TagMan genotyping for 302 patients with iRM and 300 women with normal reproduction was performed. It has been shown that carriage of unfavorable genotypes (Val/Ile, Val/Val) by the Val249Ile polymorphism of the CX3CR1 gene increases the risk of developing iRM by 1.43 times. Search for associations of genes allelic variants of HLA class 2 complex with iRM revealed *501 allele in DQA1 locus, *0301 in DQB1 locus, *10, *12, *15, *16 alleles in DRB1 locus, which increases the risk of developing iRM in Kazakh population with OR from 1.34 to 4.5. As a result of the study, obtained highly significant associations of immune response genes with the development of iRM in the Kazakh population indicate the possible involvement of the immune system interaction of mother cells with syncytiotrophoblast, which is realized by vascularization defects, defective embryo implantation, and leads to early pregnancies’ termination.