History Of Recurrent Miscarriage Research Articles

Placental Site Trophoblastic Tumor – A Rare Gestational Trophoblastic Disease: A Case Report and Review of Literature

Abstract Placental site trophoblastic tumor (PSTT) represents a rare form of gestational trophoblastic disease. It occurs commonly in females with a history of miscarriage, termination of pregnancy, or any other ongoing pathological pregnancy. We report this rare case in a 23-year-old female, who previously had a history of recurrent miscarriages. In this case, we emphasize on clinical and histopathological features for better understanding and awareness of such rare entities.

The Association between Histidine-Rich Glycoprotein rs10770 Genotype and Recurrent Miscarriage in Iranian Women.

Recurrent miscarriage (RM) is a significant reproductive concern affecting numerous women globally. Genetic factors are believed to play a crucial role in RM, making the histidine-rich glycoprotein (HRG) gene, a topic of interest due to its potential involvement in angiogenesis. This study is aimed at investigating the association between the HRG rs10770 genotype and RM. Blood samples were collected from a total of 200 women at the beginning of the study. Subsequently, a comparative analysis was conducted between the blood samples of 100 women with a history of RM (case group) and the blood samples of another 100 healthy women (control group). HRG rs10770 genotyping was performed through polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP), followed by statistical analysis to evaluate the relationship between HRG rs10770 genotype and RM. The results indicated a significant statistical difference between the C/C genotype (OR = 3.32, CI: 1.22-9.04, p = 0.01) and the C/T genotype (OR = 1.24, CI: 0.67-2.30, p = 0.47) in both the case and control groups. Additionally, a significant correlation was observed in the C allelic frequency among RM participants compared to the control group (OR = 1.65, CI: 1.06-2.58, p = 0.02). The study highlights the importance of HRG rs10770 in understanding RM, shedding light on its implications for reproductive health. Furthermore, it became evident that women carrying the homozygous C/C genotype exhibited increased susceptibility to the risk of RM.

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

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

#150 : Do Women with a History of Recurrent Miscarriage Have a Higher Risk of Obstetric and Perinatal Complications in a Subsequent Pregnancy? A Cohort Study

Background and Aims: To examine if there are any adverse obstetric and perinatal outcomes associated with a history of recurrent miscarriage (RM) among a large cohort of Chinese women in Hong Kong. Method: It is a retrospective study using prospectively collected data from 2000 to 2019. Data of obstetric and perinatal outcomes from 3112 women with history of recurrent miscarriage was collected from the Clinical Data Analysis and Reporting System database and compared to 108,012 deliveries within the same time period. Logistic regression analyses were performed, adjusting for potential confounding factors. Results: For obstetric outcomes, women with RM had significantly increased odds of gestational hypertension (OR 1.28, 95% CI 1.09-1.51) and Caesarean section (OR 1.47, 95% CI 1.36-1.60). After adjusting confounding factors, there was significantly increased odds for only Caesarean section (adjusted OR 1.55, 95% CI 1.32-1.77). For perinatal outcomes, women with a history of RM were more likely to deliver preterm (OR 1.67, 95% CI 1.47-1.91; adjusted OR 1.72, 95% CI 1.50-1.99). The incidence of small for gestational age was also significantly higher in women with a history of RM (OR 1.64, 95% CI 1.39-1.94; adjusted OR 1.70, 95% CI 1.41-1.98). There was a significant difference in the incidence of perinatal death from all causes (OR 1.48, 95% CI 1.03-2.12; adjusted OR 1.52; 95% CI, 1.11-2.32). Conclusion: An increased risk of several obstetric and perinatal complications was found in a large cohort of Chinese women with a history of two or more miscarriages, who should be offered specialist obstetric care from the start of pregnancy with an emphasis on strategies to manage the increased risk of preterm birth small for gestational age and perinatal death.

Lived experience of recurrent miscarriage: women and their partners’ experience of subsequent pregnancy and support within an NHS specialist clinic – a qualitative study

ObjectiveThis study aims to describe the lived experiences of couples with a history of recurrent miscarriage in subsequent pregnancies and their perception of clinic support and cytogenetic investigations.DesignA qualitative interview...

Progesterone-mediated immunoregulation of cytokine signaling by miRNA-133a and 101-3p in Chlamydia trachomatis-associated recurrent spontaneous abortion

miRNAs regulate the expression of various genes involved in cellular and metabolic pathways in pregnancy related complications including recurrent spontaneous abortion (RSA). Modulation of progesterone and associated pro-inflammatory cytokines by miRNAs in Chlamydia trachomatis-associated RSA is still under investigation. Present study aimed to evaluate the expression/correlation of serum-circulating miRNAs-133a, 101-3p, 320b, 146b-5p, 24, 559, progesterone and few cytokines in C. trachomatis-positive spontaneous aborters. Non-heparinized blood and urine was collected from 120 patients with history of RSA (Group I) and 120 patients with ≥ 2 successful deliveries (Group II) attending Department of Obstetrics and Gynecology, Safdarjung hospital, New Delhi, India. C. trachomatis detection was performed by PCR and chlamydial load by real time PCR. Progesterone concentration was estimated by ELISA. miRNAs and cytokine expression was studied by quantitative real-time PCR and correlated with progesterone expression. Twenty six patients were found to be positive for C. trachomatis. miRNAs- 133a, 101-3p showed maximum upregulation in infected versus control patients. miRNA expression showed positive correlation with chlamydial load. Progesterone concentration showed significant decrease while cytokines (IL-6, IFN-γ, TNF-α) were significantly upregulated in C. trachomatis-positive patients. Positive correlation was observed between expression of miRNAs-133a and 101-3p and cytokines while negative correlation was observed with progesterone in infected RSA patients. Correlation between progesterone and cytokines was found to be significantly negative in infected RSA patients. Although further validation is required, the study concludes that miR-133a and 101-3p are of clinical importance and have a role in immunoregulation of progesterone and cytokines in infection associated RSA.

Characterization of vaginal Lactobacillus species as a predictor of fertility among Iranian women with unexplained recurrent miscarriage and fertile women without miscarriage history using machine learning modeling.

Lactobacillus spp. are the predominant bacteria of the vaginal tract, the alteration of which has been previously linked to miscarriage. Here, we investigated differences between selected vaginal Lactobacillus species of women with a history of recurrent miscarriages and fertile women without a history of miscarriage in Iran. Vaginal swabs were taken from 29 fertile and 24 infertile women and quantitative real-time PCR (qPCR) assay was used to determine a selection of vaginal Lactobacillus species in both groups. The logistic regression (LR) model, Naive Bayes (NB) model, support vector machine model (SVM), and neural network model (NN) were developed to predict disease outcome by selected variables. LR analysis was used to construct a nomogram indicating predictions of the risk of miscarriage. The most abundant species among the patients were L. rhamnosus, L. ruminis, and L. acidophilus, while L. gasseri, L. vaginalis, L. fermentum, and L. iners were more abundant in healthy subjects. The distribution of L. ruminis, L. iners, and L. rhamnosus was higher in patients, while L. acidophilus, L. gasseri, and L. fermentum were highly distributed among healthy subjects. Higher AUC in predicting the disease outcome was observed for L. gasseri, L. rhamnosus, L. fermentum, and L. plantarum. Our findings provide experimental evidence of vaginal Lactobacillus imbalance in infertile women and a suitable predictor for miscarriage based on the AUC algorithms. Further studies with larger sample size and using high-throughput technologies are needed to boost our understanding of the role of lactobacilli in miscarriage.

Influence of thyroid autoimmunity at various clinical stages of hypothyroidism on the risk of miscarriage before 20 weeks of gestation

PurposeWe aimed to clarify the influence of thyroid autoantibodies at various clinical stages of hypothyroidism on the risk of pregnancy loss before 20 weeks of gestation.MethodsWe enrolled 230 pregnant women with a history of recurrent miscarriage. Detailed clinical history, physical examination, and laboratory testing of thyroid function, antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-TG) were applied among all participants.ResultsCoexisting overt hypothyroidism and positive thyroid autoantibodies quadrupled the risk of miscarriage in women before 20 weeks of gestation (OR 4.04, 95% CI = 2.08–7.96, P < 0.001). Women with subclinical hypothyroidism (OR 1.44, 95% CI = 0.81–2.57, P = 0.132,) or who were euthyroid (OR 1.53, 95% CI = 0.86–2.73, P = 0.094) showed a non-significant risk of miscarriage even with positive thyroid autoantibodies. Thyroid-stimulating hormone (TSH) was positively correlated with the number of miscarriages rather than anti-TPO (P < 0.001 and 0.209, respectively).ConclusionCoexistence of overt hypothyroidism and thyroid autoimmunity was the only significant driver of pregnancy loss before 20 weeks of gestation.

P-546 History of caesarean births and risk of miscarriage - secondary analysis of three randomised controlled trials

Abstract Study question Does the history of caesarean births influence miscarriage risk in subsequent pregnancies? Summary answer In women with a history of 3 or more miscarriage(s), the subsequent miscarriage risk may increase with the presence and number of previous caesarean births. What is known already History of caesarean birth increases the risk of complications in subsequent pregnancies, including risks of spontaneous preterm birth. The evidence of association between caesarean births and subsequent miscarriage risk is scant and conflicting. Study design, size, duration We performed a secondary analysis of the dataset from three multicentre, prospective, double-blind, and placebo-controlled randomized trials. Study registration, duration, size, population, and intervention are as follows: 1) PROMISE; ISRCTN92644181; 2010 - 2013, 826 women with a history of unexplained recurrent miscarriages, progesterone. 2) PRISM; ISRCTN14163439; 2015 - 2017, 4038 women who experienced vaginal bleeding in early pregnancy, progesterone. 3) TABLET; ISRCTN15948785; 2011 - 2016, 940 euthyroid women with thyroid peroxidase antibodies, and miscarriages or infertility history, levothyroxine. Participants/materials, setting, methods The primary outcome for this analysis was miscarriage rate, defined as loss of pregnancy &amp;lt;24 weeks of gestation. RR with 95% CI was estimated using the Poisson regression model and adjusted for age, BMI, ethnicity, smoking status, and previous miscarriages. Random-effects two-stage individual participant data meta-analysis approach was used to account for treatment allocation effects. Subgroup analysis was conducted in women with a history of repeated miscarriages (3 or more) at randomisation. Main results and the role of chance After excluding pregnancies with incomplete data, we included 5,039 pregnancies in the final analysis. The overall miscarriage rate was 24.9% (1256/5039). In the non-specific population of women, there was no association between the history of caesarean births and subsequent miscarriage risk (aRR 1.00, 95% CI 0.86 to 1.17; 5,039 pregnancies). In contrast, for the subgroup of women with a history of 3 or more miscarriage(s) at randomisation, the miscarriage rate appears to increase with the history of caesarean births, although with some degree of statistical uncertainty (aRR 1.10, 95% CI 0.97 to 1.26; 1172 pregnancies). The association became significant when the analysis was categorised according to the number of previous caesarean births. With 1 previous caesarean birth, the miscarriage risk increased by 3% (aRR 1.03, 95% CI 1.00 to 1.06; 1080 pregnancies). This risk was increased by 37% with 2 previous caesarean births (aRR 1.37, 95% CI 1.03 to 1.83; 971 pregnancies), therefore indicating the presence of a biological gradient of effect which increases our confidence in the above findings. The history of previous caesarean births may be a valid prognostic risk factor for future miscarriage risk in women with a history of recurrent miscarriage. Limitations, reasons for caution Further analysis by the gestation at miscarriage (early vs. late), the type (elective vs. emergency), indication or cervical dilatation status at caesarean births is required to understand the possible mechanism behind this association and to better identify women at increased risk of miscarriage(s) related to caesarean births. Wider implications of the findings Our findings suggest that a history of caesarean births may be associated with a small increased risk of subsequent miscarriage risk in a subgroup of women with a history of recurrent miscarriage(s). This information may assist women and healthcare providers to reach more informed decisions regarding the mode of delivery. Trial registration number The study is registered with the OSF registry (ve5j4).

P-498 Towards precision medicine: maternal genetic profiles as determinant of adequate decidualization and reproductive success; a prospective study in oocyte donation cycles.

Abstract Study question To determine the impact of genes related to decidualization and immune cell activation as predictors for reproductive success. Summary answer Women with unfavorable genetic profiles for Human Leukocyte Antigen (HLA)-F and Killer Immunoglobulin-like Receptor (KIR) genes showed decreased pregnancy rates. What is known already KIR genes encode receptors present on uterine Natural Killer (uNK) cells that are essential during placentation and early gestation. It has been established that women of KIR AA genotype show lower reproductive success than KIR BX, due to the lack of activation of these immune cells. Additionally, another gene, HLA-F, expressed in endometrial cells, also seems to be involved in the recruitment and supplementary activation of uNKs. Certain alleles of this gene appear to decrease its expression in the uterus and hinder the processes in which it is involved during the decidualization process, decreasing implantation rates and increasing time-to-pregnancy. Study design, size, duration We conducted a prospective cohort study with 75 patients, with no history of recurrent miscarriage or implantation failure, who attended our institution to undergo assisted reproduction treatments (ART) with donated oocytes, between January 2021 and December 2022. By using the egg donation model, we were able to investigate the endometrial cell population avoiding the oocyte factor bias Participants/materials, setting, methods All patients included were under 45 years of age (40.5 ± 2.9 years), had a normal BMI (21.6 ± 1.9 kg/m2) and had not been diagnosed with uterine pathologies or immunological conditions. All recipients were genotyped for the KIR and HLA-F genes and pregnancy, miscarriage (MR) and live birth rates (LBR) obtained in their egg donation cycles were recorded. Fisher's test was used to determine statistically significant differences (p &amp;lt; 0.05) between groups Main results and the role of chance Patients were divided into two groups according to their KIR genotype: 29 KIR AA (inhibitor) and 46 KIR BX (activator). In each group, allelic load was determined for the three HLA-F regions studied (RS1362126, RS2523405 and RS2523393). For all these regions, patients with favorable HLA-F alleles and KIR BX genotype had higher pregnancy rates than KIR AA patients with unfavorable HLA-F alleles (85.42 % vs 54.17% for RS1362126 region, OR = 4.956, p = 0.008; 83.33% vs 58.62% for RS2523405 region, OR = 3.529, p = 0.0295; 82.5% vs 57.69% for RS2523393 region, OR = 3.457, p = 0.0462). No significant differences were obtained for MR or LBR. This demonstrates the involvement of KIR and HLA-F in embryo implantation and that the coincidence of unfavorable alleles for both decreases reproductive success considerably, probably due to impaired decidualization and lack of uNK recruitment and activation. No significant differences were obtained for the rest of the genetic profiles, except when comparing pregnancy rate of KIR AA women with favorable HLA-F alleles to KIR AA women with unfavorable HLA-F alleles for the RS1362126 region (79.41% vs 54.17%, OR = 3.264, p = 0.04). The latter finding suggests that the lack of uNK cell activation, so evident in KIR AA patients, could be compensated by expressing favorable HLA-F alleles. Limitations, reasons for caution The low sample size of this study does not allow us to compare groups taking into account other genes, such as embryonic HLA-C, which also, and in combination with KIR genotypes, has been shown to play a role in proper implantation and placentation. Wider implications of the findings uNKs activation is required to promote embryo implantation. Combination of unfavorable genetic profiles involved in these immune mechanism leads to lower pregnancy rate. The study of these genetic profiles can help to predict reproductive success, thus identifying patients susceptible to receive immunological treatment before embryo transfer, possibly decreasing their time-to-pregnancy. Trial registration number Not applicable

P-512 Cell-mediated immunity as a biomarker of predisposition in recurrent miscarriage.

Abstract Study question Are alterations in the peripheral cellular immune system a potential risk factor for recurrent miscarriage? Summary answer Percentage alteration of some circulating immune cell subpopulations could be used as biomarkers or potential therapeutic targets in recurrent miscarriage. What is known already About 50% of patients with recurrent miscarriage (RM) have no known cause of the disease. The maternal immune system plays an important role in maternal-fetal tolerance, so an imbalance in the maternal immune system could trigger reproductive failure in women. Antiphospholipid syndrome is the only immunological alteration with sufficient evidence of association with RM, however, there are many other immunological parameters under investigation that appear to mediate the maternal-fetal relationship such as KIR receptors and HLA-C. Other authors are focusing their studies on reproductive immunology at the cellular level, looking at the role of different lymphocyte subpopulations in RM. Study design, size, duration Prospective observational analytical study (cases and controls) conducted in the Immunology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain) from 2019 to 2022. It included a group of 49 non-pregnant women with a clinical history of recurrent miscarriages of unknown cause, and two control groups, one with 40 women of childbearing age who had at least one live newborn and another with 60 women of childbearing age who had no history of pregnancy. Participants/materials, setting, methods The inclusion criteria for the study were: two or more gestational losses (&amp;lt; 22 weeks of pregnancy). Patients with severe uterine pathologies, genetic disorders, thrombophilias, obesity, infections, coeliac disease without gluten restriction, uncontrolled endocrine disorders, immunomodulatory treatment, autoimmune disorders and documented RM were excluded from the study. An immunophenotypic study of T, B, NK and NKT lymphocyte subpopulations and monocytic series was performed. Cell characterization was carried out by 6-colour flow cytometry in peripheral blood. Main results and the role of chance When comparing the cellular profile of RM patients with the profile of both control groups, we observed alterations in the percentage levels of CD3+ T cells, CD8+ T cells, NKT cells and non-switch and class switch memory B cells in the patient group, suggesting the presence of a predominantly pro-inflammatory peripheral cellular immune profile in RM patients. In contrast to previous studies by our research group, we did not observe significant differences between the percentage levels of NK cells and activated CD8+ T cells (HLA DR+) in the patient and control groups, which may be explained by the high and exhaustive patient selection in this study. After association study of these alterations with RM, we identified levels of NKT cells &amp;gt; 5%, CD8+ T cells &amp;gt; 26.50%, non-switch memory B cells &amp;gt; 22% and class switch memory B cells &amp;gt; 32% as new biomarkers of RM risk. In addition, the combination of at least two of these new biomarkers was found to significantly increase the likelihood of developing the disease, suggesting that RM is a complex pathology in which multiple factors may influence the pathogenesis of the disease. Limitations, reasons for caution Among the limitations of our study, we can highlight the collection of control group variables from databases developed in previous studies, in addition to a small sample size. Wider implications of the findings The determination of these immunological biomarkers in RM allows us to evaluate the role of immunomodulatory therapies on these biomarkers in order to evaluate possible new treatments to help prevent immune-mediated reproductive failure, thus contributing to a more personalized medicine. Trial registration number Not applicable

The hormone-sensitive lipase C-60G polymorphism is correlated with recurrent spontaneous abortion in women with polycystic ovary syndrome

Objective(s)Disrupted lipid metabolism has been associated with the development of polycystic ovary syndrome (PCOS) in women of reproductive age. Hormone-sensitive lipase (HSL) is an intracellular lipase that has a crucial role in normal lipid metabolism. This study aimed to assess the frequency of C-60G polymorphism of HSL in healthy women and PCOS women, and its correlation with infertility and recurrent spontaneous abortion (RSA) in PCOS patients. Study designA total of 324 PCOS patients (including 199 infertile patients and 125 patients with a history of RSA and 144 healthy controls) were enrolled in this study. Biochemical parameters were measured, and the genotypes of C-60G polymorphism of the HSL gene were determined using PCR-restriction fragment length polymorphism (RFLP) techniques. ResultsThere was no significant difference in the genotype and allele frequencies of C-60G polymorphism between PCOS, PCOS-infertile woman, and non-PCOS subjects. However, a higher percentage of combined variants (CG + GG) and CG genotypes, as well as G allele was found in the PCOS-RSA group in comparison with non-PCOS women. The presence of the G allele conferred a 2.4-fold risk for RSA in women with PCOS (OR: 2.4, 95 % CI [1.22–4.70], P = 0.011). Furthermore, a significant correlation between CG or GG genotype of HSL and the level of free testosterone was observed. ConclusionAccording to the obtained results, the C-60G polymorphism in the HSL promoter was associated with PCOS-related RSA, possibly through increasing the level of free testosterone. Therefore, the rs34845087 polymorphism may be a promising prognostic biomarker for RSA in women with PCOS.

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

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

Association of functional superoxide gene polymorphism with chlamydia trachomatis-associated recurrent spontaneous abortion

Oxidative stress generated by Chlamydia trachomatis infection is associated with reproductive complications such as recurrent spontaneous abortion. Aim of prospective study was to evaluate whether single nucleotide polymorphisms (SNPs) of SOD1 and SOD2 gene are associated with C. trachomatis-infected recurrent spontaneous abortion (RSA). 150 patients with history of RSA and 150 patients with history of successful deliveries were recruited from Department of Obstetrics and Gynecology, Safdarjung hospital, New Delhi, India. Urine and non-heparinized blood samples were collected and C. trachomatis was detected by polymerase chain reaction (PCR). Using qualitative real time PCR, SNPs rs4998557 (SOD1) and rs4880 (SOD2) were screened in enrolled patients. Level of 8-hydroxyguanosine (8-OHdG), 8-isoprostane (8-IP), progesterone and estrogen was determined by enzyme-linked immunosorbent assays and correlated with SNPs. Significant differences were found in frequency of AA genotype of SOD1 gene among RSA patients versus controls, (82% and 54.66%, respectively; p = 0.02; OR 0.40; CI 95%). Frequency of AA genotype of SOD1 gene among RSA patients with C. trachomatis infection was 87.33%, while in uninfected RSA patients was 71.33% (p < 0.0001; OR 8; CI 95%). No significant relation was found between SOD2 (rs4880) genotype and RSA. Furthermore, significant increase in 8-OHdG, 8-IP and estrogen and significant decrease in progesterone was observed among patients carrying AA genotype. Findings suggest the clinical importance of AA genotype along with 8-OHdG, 8-IP and estrogen and progesterone in screening C. trachomatis-infected RSA women.

Increased cytotoxic natural killer cells in the endometrium alone cannot be considered the immunological cause of recurrent miscarriage

To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding. Prospective observational cohort study. Clinic and university laboratories. Participants included 39 women with recurrent miscarriages who had undergone invitro fertilization cycles with donated oocytes and 21 healthy oocyte donors with proven fertility. Endometrial biopsy samples were collected from both patients and donors, and the KIR genotypes of the assisted reproductive technology patients were analyzed. Endometrial gene expression (cluster of differentiation [CD] antigens and anti-inflammatory and proinflammatory interleukins) and the number and percentage of regulatory T and NK cell populations in patients and donors were determined. Subsequently, the results obtained were categorized in the group of patients by KIR genotype. Killer cell immunoglobulin-like receptor-HLA-C binding was also examined in patients, considering their KIRs. A higher percentage of CD56dimCD16+ NK cells were observed in patients than those in healthy donors. Nevertheless, when categorizing patients by KIR genotype and comparing the KIR AA (35.9%), AB (43.6%), and BB (20.5%) groups, no statistically significant difference was observed in either endometrial gene expression or any of the immune cell populations analyzed. Finally, no differences in binding between KIR and HLA-C molecules were registered among these 3 sets of patients. The reported increase in the number of NK cells with a cytotoxic profile in the endometrium of women with a history of recurrent miscarriages cannot alone explain these events because no relationship is observed between such cellular increase and the KIR genotypes, which individually, and in combination with the different HLA-C alleles, have also been associated, by previous studies, with negative reproductive outcomes. 1405-MAD-025-JG.

Possible Role of Leukemia Inhibitory Factor and Inflammatory Cytokines in The Recurrent Spontaneous Abortion: A Case-Control Study.

Despite of long-lasting efforts, in more than 50% of cases, the etiology of recurrent spontaneous abortion (RSA) remains unknown. Leukemia inhibitory factor (LIF) has an essential role in the reproductive process, such as modulating inflammatory responses. This study aimed to evaluate the relationship between the LIF gene expression as well as serum levels of inflammatory cytokines and occurrence of RSA in infertile women with a history of RSA. In this case-control study, the relative gene expression levels of LIF, concentrations of tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-17 were measured in peripheral blood and serum of women with a history of RSA (N=40) compared with non-pregnant and fertile women as the control group (N=40) using quantitative real-time polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively. The mean age of patients and controls was 30.1 ± 4.28 and 30.03 ± 4.23, respectively. Patients had a history of at least 2 and at most 6 abortions. The mRNA levels of LIF were significantly lower in the women with RSA in comparison with the healthy participant (P=0.003). Regarding cytokine levels, no significant difference was seen between the two groups (P≥0.05). There was no correlation - between the LIF mRNA levels and TNF-α and IL-17 serum concentrations. The U-Mann-Whitney test and the Pearson correlation coefficient were applied to comparison variables between groups as well as a correlation between LIF mRNA and cytokine levels in serum. Despite a significant reduction in the LIF gene mRNA level in patients with RSA, it was not associated with increases in inflammatory cytokines. Dysfunction in the production of LIF protein may be involved in the onset of RSA disorder.

Testosterone, sex hormone-binding globulin and dehydroepiandrosterone levels and cervical length of Egyptian women with a history of recurrent miscarriages, polycystic ovary syndrome and without the conditions at three stages of pregnancy

Total testosterone (TT), sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA) levels, and cervical length (CL) were investigated in pregnant Egyptian women with polycystic ovary syndrome (PCOS, n = 38), history of miscarriages (RM, n = 40) and without the conditions (HC, n = 40). At week 8, the RM had lower levels of TT (p = 0.000) and free androgen index (FAI) (p = 0.000) and higher SHBG (p = 0.000) and DHEA (p < 0.05) than the PCOS. Compared with the HC, they had elevated SHBG (p < 0.05) and DHEA (p = 0.001) and reduced CL (p = 0.000). TT (p = 0.001) and FAI (p = 0.000) were higher and SHBG (p = 0.000) and CL (p = 0.001) lower in the PCOS than in the HC group. At week 16, TT (p = 0.000) and FAI (p = 0.000) were higher, and SHBG (p = 0.000) and CL (p < 0.05) lower in PCOS than in RM and HC. The PCOS had elevated FAI than the RM (p = 0.000) and HC (p = 0.001) at week 20. The DHEA, SHBG and CL abnormalities in PCOS and RM may compromise pregnancy outcomes. IMPACT STATEMENT What is already known on this subject? Hyperandrogenaemia, low sex hormone-binding globulin (SHBG), shortened cervical length (CL) and polycystic ovary syndrome (PCOS) are the most cited risk factors for recurrent miscarriages (RM). However, the published data are inconsistent, perhaps because of the confounding effects of ethnicity and nutritional milieu. What do the results of this study add? The study’s findings comprising ethnically and socially homogenous women demonstrate that PCOS and RM are characterised by elevated dehydroepiandrosterone (DHEA) and shortened CL, and PCOS by reduced SHBG. These abnormalities would be expected to have an adverse impact on pregnancy outcomes. What are the implications of these findings for clinical practice and/or further research? Twenty-weeks DHEA and CL values have the potential to predict outcome risk in women with a history of RM and PCOS. Further research on other population groups is required to validate the current study’s findings.

Diverse cardiovascular risk of recurrent spontaneous abortion: A prospective cohort study using UK Biobank

Previous studies have reported that history of recurrent spontaneous abortion (RSA) can increase the risk for cardiovascular disease. However, previous studies mainly focused on atherosclerotic cardiovascular disease (ASCVD), such as coronary artery disease or stroke, hence the effect of RSA on non-atherosclerotic cardiovascular diseases (non-ASCVD) remains unknown. In the current study, we examined if women with a history of RSA have an increased risk for long-term cardiovascular outcomes including both ASCVD and non-ASCVD. The UK Biobank is a prospective cohort study that recruited participants 40 to 69 years old with ongoing follow-up. Among women enrolled in UK Biobank, those with at least one pregnancy history and without pre-existing cardiovascular disease were included. The new occurrence of ASCVD and non-ASCVD after enrollment were compared between the women with RSA history and without RSA history. To evaluate the incidence of cardiovascular outcomes, a Cox proportional hazard model was used with adjustment for covariates including age, race, BMI, nulliparity, use of hormones, smoking, early menopause, hysterectomy, prevalent diseases, and medication by Cox proportional hazards regression analysis. In the presence of a history of RSA, the risk of new occurrence of overall cardiovascular disease, was higher (adjusted hazard ratio (aHR), 1.24 (95% CI 1.15-1.35), Figure 1). Specifically, the incidence of coronary artery disease, myocardial infarction, peripheral artery disease, heart failure, mitral regurgitation, atrial fibrillation/flutter were all increased in cases with a history of RSA (Figure 2). The women with history of RSA had an increased long-term risk of not only ASCVD, but also non-ASCVD.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Features of the expression of STAT1 and STAT3 mRNA by monocytes of women with a history of recurrent miscarriage

Features of the expression of STAT1 and STAT3 mRNA by monocytes of women with a history of recurrent miscarriage

Complete Uterine Septum, Double Cervix and Vaginal Septum (U2b C2 V1): Hysteroscopic Management and Fertility Outcomes—A Systematic Review

complete uterine septum, double cervix and vaginal septum is a rare complex Müllerian anomaly affecting patients' quality of life in terms of fertility and pelvic pain. The aim of our review is to gather the studies concerning the diagnosis and treatment this complex malformation and to describe the related fertility outcomes. this study was conducted in 2022, according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the protocol was submitted to the International Prospective Register for Systematic Reviews (PROSPERO). PubMed, Scopus and Web of Science electronic databases were searched to find eligible articles. In total, 538 articles were identified through literature research. A total of ten articles satisfied the eligibility criteria and were included in the systematic review. 86 affected women were evaluated, and 71 of them were treated. Almost all patients included in our research presented with primary infertility or with a history of recurrent miscarriages; half of all patients also reported dyspareunia. After surgical treatment, 47 pregnancies were achieved: 41 live birth and ongoing pregnancies and six spontaneous miscarriages occurred; a significantly lower miscarriage rate was reported after surgical treatment. hysteroscopic treatment of U2b C2 V1 anomaly can be safely performed, leading to favorable fertility outcomes, measured as the achievement of pregnancy and a reduction in miscarriage rate.