History Of Recurrent Pregnancy Loss Research Articles

Effects of hysteroscopic septum incision versus expectant management on IVF outcomes in women with complete septate uterus: a retrospective study

ObjectiveThis retrospective study aimed to assess the impact of hysteroscopic septum incision on in vitro fertilization (IVF) outcomes among infertile women diagnosed with a complete septate uterus and no history of recurrent pregnancy loss.MethodsThe study was conducted at a tertiary reproductive center affiliated with a university hospital and involved 78 women with a complete septate uterus. Among them, 34 women underwent hysteroscopic septum incision, while 44 women opted for expectant management. The primary outcome measure was the live birth rate, while secondary outcomes included clinical pregnancy rate, preterm birth rate, miscarriage rate, and ongoing pregnancy rate.ResultsWomen who underwent hysteroscopic septum incision demonstrated a comparable likelihood of achieving a live birth compared to those managed expectantly (25% vs. 25%, Relative Risk (RR): 1.000, 95% Confidence Interval (CI): 0.822 to 1.216). No preterm births occurred in either group. The clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate showed no significant differences between the surgical group and the expectant management group. Subgroup analyses based on the type of embryo transferred also revealed no significant differences in outcomes.ConclusionsHysteroscopic septum incision does not appear to yield improved IVF outcomes compared to expectant management in infertile women with a complete septate uterus and no history of recurrent pregnancy loss.

An Unusual Presentation of Primary Anti-phospholipid Antibody Syndrome as Acute Coronary Syndrome in Young – A Case Report

A case report of a 32-year-old female patient without any traditional risk factors presented with angina to our hospital within 6 h. Her electrocardiogram (ECG) showed extensive anterior wall -ST elevation myocardial infarction (MI). She was treated with thrombolytic therapy in the form of tenecteplase and was given standard treatment for acute coronary syndrome (ACS). Her history revealed three recurrent pregnancy losses and a history of preeclampsia. Echocardiography showed regional wall motion abnormalities of the mid, distal, apex, and anterior wall with severe left ventricular systolic dysfunction. Routine blood investigations showed elevated total leukocyte count with neutrophilic predominance. With a history of recurrent pregnancy loss, she was investigated for anti-phospholipid anti-phospholipid antibody syndrome (APS) and was found to have positive lupus anticoagulant 1. She underwent coronary angiography (CAG) which showed a left main shaft 40% stenosis with an ulcerative lesion containing thrombus in the ostioproximal to mid-left anterior descending artery (LAD), other coronary arteries were normal. She was managed conservatively with glycoprotein IIb/IIIa inhibitor (Tirofiban) and switched to oral anticoagulation with Vitamin K antagonist (VKA-Acenocoumarin) along with dual-antiplatelet therapy.

Evaluation of endometrial receptivity in recurrent pregnancy loss and recurrent implantation failure.

The cause of implantation defects in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) has not been clearly established. We aimed to evaluate the immunohistochemical changes in HOXA-11, β1 integrin, focal adhesion kinase (FAK), cluster of differentiation 44 (CD44), and extracellular matrix protein 1 (ECM1) molecules during the receptive endometrial period in patients with RIF and RPL. This study was retrospectively conducted at a university hospital. After the exclusion of cases with pathology that may cause a change in the level of receptors in the endometrium, biopsies performed during the receptive period were selected, and the patients were categorized into RPL (n=15), RIF (n=16), control (n=16) groups. All preparations were immunohistochemically stained for HOXA-11, β1 integrin, FAK, CD44, and ECM1. HOXA-11 and β1 Integrin expression changes were similar between the RIF and control groups. However, FAK expression was significantly increased in the RIF group (p<0.01). Additionally, ECM1 and CD44 expressions were significantly decreased in the RIF group compared with the control group (p<0.01). There was no significant difference in the endometrial staining of HOXA-11, FAK, and ECM1 in patients with a history of RPL. However, β1 Integrin and CD44 levels were significantly decreased in the RPL group compared with the control group (p<0.05). Implantation is a complex process, and altered adhesion mechanisms involved in endometrial receptivity may be related to defective implantation in patients with RIF and RPL. Among the adhesion molecules, the expression of CD44, β1 integrin, FAK, and ECM1 molecules varies in inappropriate implantation compared with the normal population.

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

Pregnancy is a state of happiness and hope not only for a woman but for her family as well as near and dear ones. However, this phase of happiness comes shattering down for some couple who are not able to successfully complete pregnancy and end up losing a baby in the early stages of pregnancy. Recurrent pregnancy loss (RPL) is prevalent among Omani women and the psychosocial impact of RPL is heavy upon these young women devastating their overall quality of life. Researchers conducted a cross sectional survey among 184 Omani women who had a history of recurrent pregnancy loss in a pioneering teaching tertiary care hospital. Data collection done from using a self-reported questionnaire to assess the depression, anxiety and RPL associated stress of women with history of RPL The mean age of women with RPL was 34.05 and 81% reported 2-3 pregnancy loss. Participants reported higher mean scores of depression (9.94), Anxiety (10.32) and fertility related stress (30.28). Women with multiple pregnancy losses (above 3) reported higher level of anxiety which was significant at (p<0.05%) The findings from current study also indicated that women with RPL experience higher levels of depression, anxiety, and fertility related stress.

A history of recurrent pregnancy loss is associated with increased perinatal complications, but not necessarily a longer birth interval: a population study spanning 18 years.

Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)? Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth). There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition. We conducted a population-based retrospective cohort study of 184241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates. Among individuals with at least two recorded live births between 2000 and 2018, 12321 patients with RPL and 171920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach. The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL. This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses. The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child. This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest. NCT04360564.

Influence of forkhead box protein 3 gene polymorphisms in recurrent pregnancy loss: A meta-analysis

BackgroundTreg cells play an important role in development of tolerance in maternal immune system against the semi-allogenic embryo. Human forkhead box protein 3 (FOXP3) gene, is the major transcription factor responsible for the regulation of Treg function during pregnancy. Single nucleotide polymorphisms (SNPs) of FOXP3 gene have been reported as a risk factor for Recurrent Pregnancy Loss (RPL), however, results from previous studies are inconsistent. MethodologyWe have collected data from different studies to investigate the overall association of FOXP3 SNPs with risk of RPL. PubMed, Google Scholar, Elsevier, and Cochrane databases were searched to identify eligible studies. Odds Ratio (OR) and 95 % Confidence Interval (CI), calculated via fixed effect or random effect models, were used to evaluate strength of association. This meta-analysis included 11 studies (1383 RPL cases and 1413 controls) of 6 SNPs: rs3761548 A/C, rs2232365 A/G, rs2294021 T/C, 2280883 T/C, rs5902434del/ATT and rs141704699C/T, with ≥2 studies per SNPs and at least 1 significant result. ResultsWe observed that FOXP3 polymorphism was predominantly present in Asian women with history of RPL. rs2232365 A/G, rs3761548 A/C, rs2294021 T/C, rs2280883 T/C and rs5902434del/ATT polymorphisms were significantly associated with risk of RPL in Indian population. Further, among the most commonly seen polymorphism, rs3761548 A/C was significantly associated with risk of RPL in women from Kazakhstan, China and Gaza, Palestine; rs2232365 A/G in populations of Kazakhstan, Egypt, Iran and Gaza, Palestine. Results of this study indicates that FOXP3 polymorphism is significantly associated with risk of RPL, especially in Asians.

Circulating levels of cytokines (IL-6, IL-10 and TGF- β) and CD4+CD25+FOXP3+Treg cell population in recurrent pregnancy loss

Recurrent pregnancy loss (RPL), a serious reproductive health issue, characterized by two or more pregnancy losses before 20th week of gestation. Globally, it affects 2–5% couples and the basis of the crisis is still unknown in 50% cases. Successful pregnancy is associated with pro and anti-inflammatory gestational phases that tolerate the semi-allogenic foetus, and disturbance leads to pregnancy complications like RPL. This case-control study aimed to assess the inflammatory status in the mid-gestation of ongoing pregnancy of women with (RPL) and without (NRPL) the history of RPL. Blood samples were processed for PBMC isolation, subjected to Flow-cytometry for CD4+CD25+FOXP3+Treg-cell population count and serum samples for IL-6, TGF-β, IL-10 cytokine levels (ELISA). Significant reduction in the percentage of Treg cells, and elevated values for IL-6/TGF-β and IL-6/IL-10 ratios were observed in RPL over NRPL group (p = 0.0001). Opposing results were seen with respect to the magnitude of history of RPL (2 vs. >2 losses). ROC curve analysis showed the superior discriminatory ability of cytokine ratios (IL-6/TGF-β > IL-6/IL-10) for RPL over Treg cells. Our findings are suggestive of pro-inflammatory dominance in mid-gestation of pregnant women with a history of RPL in general and greater than normal anti-inflammatory milieu in cases with > 2 pregnancy loss. As both sterile and infection related inflammation plays a role in pregnancy loss, studies enrolling women with favourable and unfavourable ongoing pregnancies may shed light on the importance of the present study for developing better management/therapeutic strategies.

740 Maternal history of recurrent pregnancy loss and placental related complications

740 Maternal history of recurrent pregnancy loss and placental related complications

Metroplasty increases the take-home baby rate by reducing pregnancy loss without changing the chance of conception in women with septate uterus: a retrospective, single-center, observational study

BackgroundAlthough abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center.MethodsThis retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins’ method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women.ResultsSeventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio.ConclusionsBoth abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy.Trial registrationNot applicable.

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

To evaluate the risk of metabolic syndrome (MS) after recurrent pregnancy loss (RPL) using UK Biobank data. A history of pregnancy loss is associated with the development of cardiovascular diseases in the future. However, the association between RPL and subsequent MS is poorly understood. Therefore, we aimed to check the risk of MS after RPL. The study population was divided into 2 groups according to reproductive history: women with a history of RPL and women without a history of RPL. Recurrent pregnancy loss was defined as 2 or more spontaneous miscarriages, and MS was defined as at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, high-blood pressure, and hyperglycemia. UK Biobank resource. The UK Biobank is a prospective cohort study that enrolled individuals aged between 40 and 69 years whose medical and reproductive histories were retrieved at enrollment. In this cohort, only women with a history of at least one pregnancy were selected. Recurrent pregnancy loss. The primary outcome was the prevalence of MS. The secondary outcomes were 5 diagnostic components of MS. We analyzed 228,674 women, including 15,702 with a history of RPL and 212,972 without a history of RPL. Women with a history of RPL have a higher prevalence of MS between the ages of 40 and 60 years (33.0% vs. 31.5%). After adjusting for covariates (age, race, number of live births, early menopause, smoking, alcohol consumption, and physical activity), the increased risk of MS after RPL remained significant (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.15). Furthermore, in the analysis of the 5 diagnostic components of MS, a history of RPL significantly increased the risk of abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hyperglycemia. Middle-aged women with a history of RPL have an increased risk of MS.

Pregnancy with uterine didelphys and history of recurrent pregnancy loss: Case report

Link of Video Abstract: https://youtu.be/H7Y7XoPOUAw Background: Uterine didelphys is an embryologic disorder that arises from the failure of Mullerian duct fusion. It is characterized by the presence of two distinct cervices, two vaginas, and two uterine horns. Obstetric complications may arise during pregnancy when uterine didelphys is present; these may include spontaneous abortion, premature labour, and fetal malpresentation. Case Presentation: A 25-year-old woman has been married for three years and had history of six gravid, zero parity, and five abortion. The patient had uterine didelphys. A fully septated uterus with double cervices and vaginas was found on pelvic magnetic resonance imaging. The patient arrived at the hospital at 27/28 weeks. Periodic sonograms demonstrated breech presentation and no (Intrauterine Growth Restriction) IUGR evidence. At 38/39 weeks, the patient was scheduled for cesarean surgery. Uterine didelphys morphology, pregnancy on the left side of the uterus, and the septum separating the left and right uterine cavities were all observed during the caesarean section. The newborn had three umbilical cords wrapped around his neck. The infant was female, 2800 grams, 48 cm, Apgar score 7-8, Ballard score (BS) 38 weeks, Lubchenco score (LS) p25-50. Conclusion: Antenatal care is required for investigating risks of uterine didelphys, including cervical incompetence, spontaneous abortion, and preterm birth, using serial sonograms to assess fetal well-being and cervical length.

Case Report On Abnormal Uterine Bleeding with Multi-System Disorders

Autoimmune disease is a condition that attacks the immune system and leads to multi-system disorders like systemiclupus erythematosus and rheumatoid disorders, which initiates self-directed immune responses that result in clinical diseases,mainly in obstetrics conditions like recurrent pregnancy loss, pre-eclampsia are common. The study aimed to identify therelationship between connective tissue disorders and abnormal uterine bleeding patterns. A rare case of abnormal uterinebleeding with a past history of recurrent pregnancy loss was presented in the casualty with excessive menstrual bleeding in astate of hypovolemic shock. The patient complained of generalised malaise, giddiness, breathlessness, and palpitations for thepast 2 months. She suffered recurrent epistaxis for the past 2 months and experienced symptoms like loss of appetite, recurrentvomiting for the past 15 – 20 days, and rashes over the face and cheeks for 6 months. Her haemoglobin was 2.4g/dL, and theplatelets were less than 10,000 with bicytopenia at the time of admission She was shifted to ICU and haemodynamicallystabilized by packed red blood cells, fresh frozen plasma, and platelets. Following this, she was treated with antifibrinolytics, andsevere anaemia was corrected with multiple PRBC transfusions. Multiple single-donor platelet transfusions were also done. Afterrecovery, the patient was discharged with an advice to continue hydroxychloroquine. Immune dysregulation and inflammationtogether contribute to the development of menstrual disorders among women with Rheumatoid Disorders which can be wellmanaged with systematic therapeutic plans at the initial stage.

Prevalence of Hypothyroidism in Pregnancy and Its Associations with Adverse Pregnancy Outcomes Among Pregnant Women in A General Hospital: A Cross Sectional Study.

Hypothyroidism affects 3-5% of all pregnant mothers, making it the most common thyroid disorder associated with pregnancy. Furthermore, it is associated with adverse outcomes of pregnancy and newborn. Therefore, this research is aimed at determining the magnitude and pregnancy adverse outcomes associated with hypothyroidism among pregnant women having maternity services in a general hospital in Somalia. A cross-sectional study was conducted on pregnant women who delivered in the hospital between December 2022 and May 2023. Subjects were selected through systematic sampling and data collected through an interviewer-based questionnaire. Adjusted odds ratios (AORs) of P values and 95% confidence intervals (CIs) were used to assess the correlation between variables. The prevalence of hypothyroidism was 23.6% (95% CI: [19.4-27.8]). Overt DM (AOR=9.125, CI (3.106-26.812)), History of Recurrent pregnancy loss (AOR=12.938, CI (4.958-33.763), hypertension during pregnancy (AOR=6.718, CI (2.326-19.994)) and preterm delivery (AOR=7.015, CI (3.234-13.958)) were variables associated with hypothyroidism in pregnancy. The study has shown a high prevalence of hypothyroidism during pregnancy at Daruxannan Hospital compared to previous studies around the world. This finding highlights the need for national and regional surveys to identify the prevalence and associated factors that contribute to hypothyroidism in pregnancy to set up interventions and determine policy directions.

What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping?

BackgroundBalanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT).Material and methodsFrom January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements.ResultsIn the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6–3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1–99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages.ConclusionsOur study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies.

Depression, anxiety, and stress and adverse pregnancy outcomes in pregnant women with history of recurrent pregnancy loss in Nigeria.

The primary purpose of this study was to examine whether pregnant women with a history of recurrent pregnancy loss (RPL) are more likely to experience moderate-to-severe depression, anxiety, or stress symptoms than pregnant women without a history of RPL. The secondary purpose was to determine whether women with prior RPL experienced more unfavorable pregnancy outcomes if they had depression, anxiety, or stress. A prospective case-control study was conducted that included 47 pregnant women with a history of RPL and 94 pregnant women without prior RPL. Participants 20weeks of gestation or earlier were included. Both groups completed the Depression, Anxiety, and Stress Scale (DASS-21), and were followed up until delivery to determine the pregnancy outcomes. Multivariate logistic regression was used to compare adverse pregnancy outcomes. Among the 47 women with prior RPL, 10 had primary RPL (two or more miscarriages without a successful pregnancy) and 37 secondary RPL (two or more miscarriages with a history of successful pregnancy). RPL was significantly associated with moderate-to-severe levels of depression (P < .001), anxiety (P < .001), and stress (P < .001). Among the RPL group, high stress level was significantly associated with repeat miscarriage (adjusted odds ratio (AOR) = 5.28, 95%CI = 1.25-100.0, P = .03) and preterm labor (AOR = 6.07, 95%CI = 1.61-100.0, P = .04). Depression and anxiety were not associated with adverse pregnancy outcomes. Pregnant women with a history of RPL had considerably higher rates of moderate-to-severe depression, anxiety, and stress. Repeat miscarriage and preterm labor were considerably higher among pregnant women with RPL who were experiencing high stress levels at baseline.

Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder.

Recurrent pregnancy loss (RPL) refers to two or more miscarriages before 20 weeks gestation. Its prevalence is 1-2%; its pathogenesis remains unexplained in more than 50% of cases, in which the cause is thought to be abnormal immune activity during placentation leading to a lack of pregnancy-induced immune tolerance. It is unknown whether immune activity is deranged in the endometrium of women with RPL. We studied the gene expression and the quantitative tissue protein levels of three immune checkpoints (CD276, which enhances cytotoxic T-cell activity, cytotoxic T-lymphocyte-associated antigen-4 [CTL-4], which reduces Th1 cytokine production, and lymphocyte activation gene-3 [LAG-3], which shows suppressive activity on Tregs and CD4+ T-cells) in endometrial samples from 27 women with unexplained RPL and in 29 women with dysfunctional uterine bleeding and previous uneventful pregnancies as controls. RNA isolation, real-time PCR, protein isolation, and ELISA were performed. CD276 gene expression and protein tissue levels were significantly lower in the endometrium of the RPL group than in the controls, whereas both CTL-4 and LAG-3 were significantly higher. This difference suggests defective endometrial immune regulation and overactivation of immune response in women with a history of RPL, at least in relation to controls with dysfunctional uterine bleeding and previous normal reproductive history.

Treatment of recurrent pregnancy loss in women with euthyroid-based thyroid peroxidase antibody syndrome.

Recurrent pregnancy loss (RPL) due to thyroid peroxidase antibody (TPOAb) syndrome remains a significant challenge in pregnancy. The current study offers better insights into miscarriages that occur due to the presence of TPOAb with euthyroid in pregnant women with a history of RPL. Out of the 347 women confirmed with unexplained RPL, only 70 (20.2%) tested positive for TPOAb (215±53). After eight women were excluded from the study due to failure to follow up, 62 participants (age range: 33±4.8 years; body mass index (BMI):25-30kg/m2 (58%) and >30kg/m2 (42%)) were included. The TPOAb-dependent RPL patients were divided according to their RPL types into 23 (30.7%) nulliparous (1˚) and 39 (69.3%) multiparous (2˚) patients, respectively. Out of the sample, 69.2% and 30.8% had a history of miscarriages during the 1st and 2nd trimesters, respectively. For treatment purposes, while screening for the TPOAb, the women received 50µg/day of L-thyroxine (LTx) for three months prior to pregnancy and during the first three months of pregnancy and were followed up until giving birth or miscarriage. Thyroxine treatment was correlated to successful normal births in 56.6% and 21.2% of pregnant women after 36 and during 28-36 weeks of gestation, respectively. However, miscarriages occurred in 18.1% and 4.1% of patients during 14-28 weeks and before 14 weeks of gestation, respectively. The current findings show the promising use of thyroxine in the control of RPL caused by euthyroid-based thyroid peroxidase antibody syndrome. This treatment has led to a significant number of women experiencing successful full-term pregnancies and giving birth to healthy babies.

11:20-11:30 - Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss

11:20-11:30 - Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss

P-540 Improper placentation due to skewed Oct4-Cdx2 expression may be a leading factor in idiopathic recurrent pregnancy loss (RPL) cases from Assam, India.

Abstract Study question Does the differential expression of key embryonic stem cell (ESC) markers due to upstream signaling cascade(s) deregulation influence RPL pathogenesis in the studied population? Summary answer Imbalanced Oct4-Cdx2 expression linked differential ESCs polarization due to β-catenin signaling deregulation during the peri-implantation period impacts RPL pathogenesis in the studied population. What is known already RPL affects approximately 2-5% of women globally and around 7% Indian women in reproductive age group; with 50% of case etiology being unclear. Proper placentation is indispensable for establishment, continuation, and success of a pregnancy; and it depends largely on a healthy balance between apoptosis and stem cell differentiation that aids proper trophoblast invasion. These differentiation events are tightly controlled by the interplay of oxygen tension, hormones, growth factors, other signaling molecules and most importantly by transcription factors including those deciding the stem cell lineage like Oct4, NANOG, and Cdx2, wherein, β-catenin is known to enhance Oct-4 activity in ESCs. Study design, size, duration The sample size was predicted using Raosoft software utilizing the prevalence rate of RPL. Overall 87 women with 2 or more pregnancy losses before completion of 20 weeks of gestation were enrolled as RPL cases with informed consent, whereas, for the control group, 107 women volunteers undergoing medical termination of pregnancy (MTP) were enrolled as gestation-week-matched comparative study group for experimental data analysis. Participants/materials, setting, methods Products of conception (POC) was collected from the MTP and RPL cases. POCs were collected in 2vials for every subject: (i) 4% buffered formalin for fixation and preparation of microscopic slides for immunofluorescence (IF) based protein expression of Oct4 and Cdx2; (ii) RNA later solution for site specific transcriptional analysis of Oct4, NANOG, Cdx2, and β-catenin utilizing Realtime PCR. The difference in expression was analyzed using SPSS statistical software. Main results and the role of chance IF based site specific protein expression data confirmed higher expression of OCT4 in RPL cases compared to MTP controls, whereas CDX2 expression was found to be low in RPL compared to MTP subjects. The Realtime PCR amplification of cDNA using β-actin as internal normalization control for Oct4 (25.76 ± 10.17 folds) and NANOG (18.32 ± 6.67folds) showed increased expression whereas the Cdx2 expression was downregulated (0.487 ± 0.186 folds) in RPL cases compared to MTP controls, indicating a shift towards pluripotency which is a non-favorable environment for the ongoing pregnancy since cell polarization for initiation of differentiation to different cell lineages is required at that time of gestation. The cdx2 and oct4 expression correlated inversely and significantly {Pearson’s correlation= −0.838, p = 0.009; Spearman’s rho= −0.786; p = 0.016}. The realtime PCR amplification of β-catenin, the key molecule involved in direct enhancing of Oct4 expression during gestation was found to be increased in RPL cases compared to MTP controls. Statistically, the β-catenin-Oct4 expression correlated positively significantly. Limitations, reasons for caution Being a patient based study, the present study is limited to being an associative study only; and therefore secondary validation of the data for causal association using cell lines or suitable model system futuristically may add valuable scientific inputs and aid clinical intervention modalities for controlling RPL. Wider implications of the findings As the majority of RPL pathogenesis etiology is undefined limiting the possibilities of clinical interventions therefore we presume the present data can layout possible therapeutic interventions by regulating key regulators influencing skewed ESC profile aiding proper placentation leading to successful pregnancy in a subpopulation of cases with RPL history. Trial registration number Not applicable

C4d Staining Is Present in Normal Placentas From Pregnancies Prior to Pregnancy Loss Associated With Chronic Histiocytic Intervillositis and Is Reduced by Immunomodulatory Therapy in Subsequent Pregnancies.

Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcomes and high recurrence risk. Recent studies suggest that CHI may represent a host-vs-graft rejection, and that C4d immunostain can be used as a marker for complement activation and antibody-mediated rejection in the CHI. This retrospective cohort study focused on 5 fetal autopsy cases associated with CHI (5 index cases) from 5 women. We analyzed placentas from the index cases (fetal autopsy cases associated with CHI) and placentas from the women's previous and subsequent pregnancies. We assessed the presence and extent of CHI and C4d immunostaining in these placentas. We evaluated each available placenta and graded the severity of CHI as either <50% or ≥50%. Additionally, we conducted C4d immunostaining on one representative section from each placenta and graded the staining levels as follows: 0+ for staining <5%; 1+ for staining between 5% and <25%; 2+ for staining between 25% and <75%; and 3+ for staining ≥75%. Three of the 5 women had pregnancies prior to their index cases (fetal autopsy cases associated with CHI). Despite the absence of CHI in their initial pregnancies, the placentas displayed positive C4d staining with grades of 1+, 3+, and 3+, respectively. These results suggest the presence of complement activation and antibody-mediated rejection in placentas from their prior pregnancies without CHI. Three of the 5 women received immunomodulatory therapy after experiencing pregnancy losses associated with CHI. After treatment, 2 of these women had live births at 35 and 37 gestational weeks, respectively, while the third had a stillbirth at 25 gestational weeks. The severity of CHI and the degree of C4d staining in the placentas decreased in all 3 cases following immunomodulatory therapies. Specifically, the level of C4d staining decreased from 3+ to 2+, 2+ to 0+, and 3+ to 1+ in these 3 cases, respectively. In women with a history of recurrent pregnancy loss associated with CHI, C4d immunostaining was present in the placentas from their previous non-CHI pregnancies, suggesting activation of the classical complement pathway and antibody-mediated reaction in their prior non-CHI pregnancies before the development of CHI in subsequent pregnancies. Immunomodulatory therapy may improve pregnancy outcomes by reducing complement activation, as shown by the reduction of C4d immunopositivity in the placentas after immunomodulatory treatment. Although we believe that the study provides valuable insights, we acknowledge that there are limitations to the findings. Therefore, to further elucidate the pathogenesis of CHI, additional research efforts with a collaborative and multidisciplinary approach are necessary.