Spontaneous Early Pregnancy Loss Research Articles

Epigenetic role of LINE-1 methylation and key genes in pregnancy maintenance

Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal–fetal crosstalk. Combined analyses of global methylation, inflammation and inherited predispositions may contribute to define pregnancy loss etiopathogenesis. LINE-1 epigenetic regulation plays crucial roles during embryo implantation, and its hypomethylation has been associated with senescence and several complex diseases. By analysing a group of 230 women who have gone through pregnancy interruption and comparing those experiencing spontaneous EPL (n = 123; RPL, 54.5%) with a group of normal pregnant who underwent to voluntary interruption (VPI, n = 107), the single statistical analysis revealed significant lower (P < 0.00001) LINE-1 methylation and higher (P < 0.0001) mean cytokine levels (CKs: IL6, IL10, IL17A, IL23) in EPL. Genotyping of the following SNPs accounted for different EPL/RPL risk odds ratio: F13A1 rs5985 (OR = 0.24; 0.06–0.90); F13B rs6003 (OR = 0.23; 0.047–1.1); FGA rs6050 (OR = 0.58; 0.33–1.0); CRP rs2808635/rs876538 (OR = 0.15; 0.014–0.81); ABO rs657152 (OR = 0.48; 0.22–1.08); TP53 rs1042522 (OR = 0.54; 0.32–0.92); MTHFR rs1801133/rs1801131 (OR = 2.03; 1.2–3.47) and FGB rs1800790 (OR = 1.97; 1.01–3.87), although Bonferroni correction did not reach significant outputs. Principal Component Analysis (PCA) and logistic regression disclosed further SNPs positive/negative associations (e.g. APOE rs7412/rs429358; FGB rs1800790; CFH rs1061170) differently arranged and sorted in four significant PCs: PC1 (F13A, methylation, CKs); PC3 (CRP, MTHFR, age, methylation); PC4 (F13B, FGA, FGB, APOE, TP53, age, methylation); PC6 (F13A, CFH, ABO, MTHFR, TP53, age), yielding further statistical power to the association models. In detail, positive EPL risk association was with PC1 (OR = 1.81; 1.33–2.45; P < 0.0001) and negative associations with PC3 (OR = 0.489; 0.37–0.66; P < 0.0001); PC4 (OR = 0.72; 0.55–0.94; P = 0.018) and PC6 (OR = 0.61; 0.46–0.81; P = 0.001). Moreover, significant inverse associations were detected between methylation and CKs levels in the whole group (rIL10 = − 0.22; rIL17A = − 0.25; rIL23 = − 0.19; rIL6 = − 0.22), and methylation with age in the whole group, EPL and RPL subgroups (r2TOT = 0.147; r2EPL = 0.136; r2RPL = 0.248), while VPI controls lost significance (r2VPI = 0.011). This study provides a valuable multilayer approach for investigating epigenetic abnormalities in pregnancy loss suggesting genetic-driven dysregulations and anomalous epigenetic mechanisms potentially mediated by LINE-1 hypomethylation. Women with unexplained EPL might benefit of such investigations, providing new insights for predicting the pregnancy outcome and for treating at risk women with novel targeted epidrugs.

Comparison of Vitamin D Status between Healthy Pregnant Women and Women with Recurrent Early Spontaneous Pregnancy Loss

Introduction: Recurrent early spontaneous pregnancy loss is the most common negative outcome of pregnancy and identification of modifiable risk factors is potentially of great importance for public health. The immunological factors may play a role in failure of pregnancy in women with recurrent pregnancy loss. The role of this vitamin D has also been proved in the immune system. Aim of the Study: This study aim to determine serum vitamin D status among women with recurrent early spontaneous pregnancy loss and to compare the vitamin D level among them with healthy pregnant women. Methods: This cross sectional comparative study was done at the out patient department of obstetrics and Gynecology in Bangabandhu Sheikh Mujib Medical University during September 2018 to August 2019. The study comprises of 70 women carrying singleton fetus, gestational age between 8 to 12 weeks, in the age range of 18 to 35 years. The respondents were divided into two groups, 35 pregnant women in their early pregnancy loss with previous history of two or more early spontaneous pregnancy loss were considered as group I and 35 women in their early live pregnancy with previous history of one or more successful pregnancy and no history of any pregnancy loss were considered as group II. Fasting serum vitamin D level was measure by CMIA. Results: This study found that most the respondents were vitamin D deficient in both groups. In group I 17(48.6%) and in group II 10(28.6%) were vitamin D severe deficient. Again in group I 18(51.4%) and 24(68.6%) in group II were vitamin D deficient. The mean vitamin D level was 9.90±2.28 ng/ml in group I and 11.43±3.96 ng/ml in group II. The differences was statistically not significant (P&gt;0.05) between two groups. There is a negative correlation (r-0.235; p 0.175) between serum vitamin D level and number of pregnancy loss. Which indicate increase number of pregnancy loss associated with decrease level of vitamin D. Conclusion: Vitamin D deficient in both groups, however the vitamin D level was comparatively low in women with recurrent early spontaneous pregnancy loss but the differences was not significant between two groups.

Placental interferon signaling is involved in chronic intervillositis of unknown etiology

IntroductionChronic intervillositis of unknown etiology (CIUE) is a placental inflammatory process associated with pregnancy loss and high recurrence risk. The pathogenesis is unclear but involves aberrant maternal inflammation. This study assesses expression of inflammatory mediators by placenta and intervillus macrophage using digital spatial profiling, which is applicable to formalin fixed paraffin embedded tissue and provides whole transcriptome expression analysis at cellular resolution. MethodsEthics approval was obtained and all experiments were performed in accordance with applicable guidelines and regulations. Archival tissue from early spontaneous pregnancy loss with high grade CIUE (4 cases) was compared to non-inflamed control normal placenta (4 cases) and granulomatous lymphadenitis as a macrophage inflammation control (4 cases). Differential gene expression between CIUE and relevant controls was assessed using unpaired t-test with Benjamini-Hochberg false discovery correction. Gene Set Enrichment Analysis (GSEA) was used to characterize and compare pathways active in the CIUE and relevant control samples. ResultsPrincipal component analysis of the gene expression data showed distinct clustering with relatively little intragroup variation in the control tissues whereas the CIUE cases are more variable. Gene expression analysis showed changes in CIUE; however, no genes remained statistically significant after correction for false discovery. GSEA revealed prominent activation of IFN-related signaling pathways in CIUE placenta, particularly IFNγ signaling. DiscussionThis study demonstrates that CIUE is associated with a specific profile of inflammatory mediators expressed by placenta villi that is dominated by IFN signaling, suggesting that uncontrolled IFNγ signaling may play a primary role in the pathogenetic mechanism underlying CIUE.

Arginine Vasopressin is not elevated in Early Pregnancy Loss

BackgroundAdministration of arginine vasopressin (AVP) has been previously shown to influence myometrial contractility during the first trimester of pregnancy in women who were undergoing a planned therapeutic abortion. Consequently, it was hypothesized that AVP may play a role in early spontaneous pregnancy loss. AVP is made in a 1:1 molar ratio with copeptin; thus, copeptin can be used as a surrogate measure of AVP. While early pregnancy loss is likely a multifactorial problem, we sought to fill the gap in knowledge of the causes of using pre‐collected samples from pregnancies that subsequently underwent spontaneous abortion and matched controls.MethodsA retrospective case control study was performed using plasma samples from the Maternal Fetal Tissue Bank (IRB# 200910784) at the University of Iowa Hospitals &amp; Clinics. Whole blood samples were collected (ACD‐A tubes, Becton Dickinson) at confirmation of pregnancy appointments in which a viable pregnancy was detected by ultrasound (6‐10 weeks gestation). Samples were processed and plasma aliquots were snap frozen and stored at ‐80oC until analysis. Control samples (N=67) from viable, healthy pregnancies were matched by gestational age, race, ethnicity, and body mass index to cases (N=123). Copeptin was measured by an automated immunoassay (Brahms KRYPTOR) and total protein concentration via a bicinchoninic acid (BCA) protein assay (Pierce). Copeptin concentrations were normalized to total protein in samples. Continuous variables were analyzed by T test.ResultsNo significant differences were detected in plasma samples that were collected while the pregnancies appeared viable. Copeptin was 7.2 +/‐ 6.0 mg/dL in case plasma samples and 6.0 +/‐ 3.4 mg/dL in control plasma samples (P=0.066). It is unclear if vasopressin increases acutely prior to the occurrence of spontaneous abortion.ConclusionThese results suggest that vasopressin cannot be used to identify pregnancies at risk of early loss at the time of pregnancy confirmation.

P–524 Is polycystic ovary syndrome really a risk factor for embryonic chromosomal aberrations? A multicenter retrospective cohort study

Abstract Study question Does the rate of embryonic chromosomal aberrations increase in the setting of PCOS independent of maternal age and BMI? Summary answer Controlling for maternal age and BMI, embryonic chromosomal aberration rate was not significantly different with controlled women undergoing preimplantation genetic testing for monogenic defects (PGT-M). What is known already It has been reported that women with PCOS have higher risk of early spontaneous pregnancy loss, and it is well known that embryonic chromosomal abnormalities play an important role as a direct factor. However, whether PCOS women have increased risk of embryonic chromosomal aberrations remains inconclusive. Study design, size, duration A multicenter retrospective cohort study was undertaken examining the incidence of chromosomal abnormalities in blastocysts using next-generation sequencing (NGS) for women undergoing PGT-M with and without PCOS (1398 PGT cycles, 5577 blastocysts) from 3 university-affiliated IVF centers between 2015 and 2019. Participants/materials, setting, methods: The blastocyst formation rate and the incidence of chromosomal abnormalities were compared between 163 PCOS women and 1235 non-PCOS women. Main results and the role of chance: Stratification analysis by maternal age with matched BMI showed no differences with regard to blastocyst formation rates for women with and without PCOS aged 20–29y (55.0% vs. 58.5%), 30–34y (54.7% vs. 58.9%) and &amp;gt;35y (56.7% vs. 52.4%), P &amp;gt; 0.05. The total embryonic chromosomal aberration rates for women aged 20–29y, 30–34y and &amp;gt;35y with and without PCOS were were also comparable, which were respectively 121/331 (36.4%) vs. 496/1209 (41.0%); 89/251 (35.5%) vs. 903/2175 (41.5%) and 72/130 (55.4%) vs. 789/1481 (53.3%), P &amp;gt; 0.05. Multivariate regression showed that controlling for maternal age and BMI, PCOS were not an independent risk factor for embryonic chromosomal abnormalities (OR = 0.89, 95% CI = 0.62 ∼ 1.35, P = 0.73). Limitations, reasons for caution The study is mainly limited by its retrospective design and relatively smaller sample size for PCOS group which carries inherent potential for bias (i.e. misclassifification and errors due to inadequate clinical notes). Wider implications of the findings: Our results indicated that chromosomal abnormalities might not be the most important causal factor for the increased risk of early pregnancy loss for women with PCOS. By contrary, the non-chromosomal embryonic aberrations and/or maternal intrauterine factors could play more important role and needs to be clarifified Trial registration number not applicable’

Correlation between Serum Vitamin D Deficiency and Early Spontaneous Pregnancy Loss

Correlation between Serum Vitamin D Deficiency and Early Spontaneous Pregnancy Loss

Study on Anticardiolipin Antibodies in Women With Recurrent Abortion in Duhok Province, Kurdistan Region, Iraq

Recurrent abortion is a worldwide issue. Anticardiolipin antibodies (ACA) are found to be among the most important factors related to recurrent spontaneous early pregnancy loss. This study aimed to investigate the prevalence of anticardiolipin IgM and IgG antibodies in women with recurrent abortion in Kurdistan Region of Iraq. The present study was conducted in Duhok and Zakho cities for the period from April 2014 to May 2019. A total of 1230 women aged between 18 to 46-year-old were included in this study. ELISA was used for the detection of anticardiolipin antibodies. Among the studied subjects, the prevalence of anticardiolipin antibodies was 74 (6.02%) for ACA IgM and 56 (4.6%) for ACA IgG. It was also observed that 16 (1.3%) subjects were positive for both ACA IgM and IgG antibodies. Additionally, the highest anticardiolipin antibody positivity rates were recorded in patients older than 30-year-old (P&lt;0.01). The IgM ACA positivity was higher in Zakho city 45 (7.2%) when compared to Duhok city 29 (4.6%) (P&lt;0.04). In conclusion, anticardiolipin antibodies can have a positive association among women with recurrent abortion. Therefore, it is suggested that women with recurrent abortion should be screened for anticardiolipin antibodies; this could increase fetal survival by initiating early anticoagulant therapy when other causes of abortion are excluded.

ЭТИОПАТОГЕНЕТИЧЕСКИЙ АСПЕКТ РАННИХ РЕПРОДУКТИВНЫХ ПОТЕРЬ ПРИ СОВЕРШЕНСТВОВАНИИ ОРГАНИЗАЦИИ МЕДИЦИНСКОЙ ПОМОЩИ ЖЕНЩИНАМ (АНАЛИТИЧЕСКИЙ ОБЗОР)

Significance. Reproductive loss is considered as a system indicator of mother and child service. The majority of spontaneous abortions occur in the first trimester. The frequency of this pathology, despite the development of medical and biological research and introduction of organizational measures, does not tend to decrease due to multifactorial nature of its etiology and pathogenesis. To reduce loss due to early spontaneous abortions, it is necessary to improve health care delivery to women through developing preventive measures with due regard to etiopathogenetic aspect of early reproductive loss. Purpose. To identify main etiopathogenetic and medico-social aspects of early spontaneous reproductive loss in order to improve organization of care delivery to women with this problem. Material and methods. Content analysis of 200 scientific publications by the Russian and foreign authors published in the main electronic databases ("CyberLeninka", "disserCat", "PubFacts", "PubMed", "Google Scholar", "eLibrary"). Results. The study analyzed major risk factors and causes of early spontaneous reproductive loss according to modern researchers. In parallel, the analysis of possible ways to improve organization of care delivery to women with spontaneous abortions at the present stage was carried out on the basis of the data obtained. Scope of application. An in-depth study of the etiology and pathogenesis of reproductive loss early in pregnancy contributes to the development of new well-founded organizational methods to reduce it. Avery described etiopathogenetic aspect should be reflected in the complex of preventive and rehabilitation measures for women with a history of early reproductive loss or at risk for miscarriage, as well as in the algorithms for managing pregnant women of these categories. The importance of a differentiated approach to patients with early spontaneous pregnancy loss and the need for their observation by doctors of different specialties are emphasized. Keywords: reproductive loss; early spontaneous pregnancy loss; miscarriage; spontaneous abortion; review; organization of care delivery for miscarriage.

The Association of Serum Vitamin D and Calcium Levels with Early Recurrent Spontaneous Pregnancy Loss

The Association of Serum Vitamin D and Calcium Levels with Early Recurrent Spontaneous Pregnancy Loss

Pregnancy-Onset Inflammatory Bowel Disease: A Subtle Diagnosis.

Inflammatory bowel diseases (IBDs) are commonly diagnosed during the reproductive years. IBD first manifested during pregnancy (pregnancy-onset IBD [POIBD]) is still an undescribed entity. The aim of the study was to evaluate the characteristics and maternal and neonatal outcomes of patients with POIBD. Data of all pregnant women with IBD within a single multidisciplinary referral clinic, IBD-MOM, between 2011-2016, were analyzed. Maternal and neonatal characteristics and outcomes were compared between the POIBD group and those diagnosed before pregnancy (non-POIBD). We identified 237 women, 31 (15%) from the POIBD group and 206 (85%) from the non-POIBD group. Eight (3.5%) patients experienced early spontaneous pregnancy loss, all in the non-POIBD group. The POIBD diagnosis occurred in 16 (52%) patients during the first trimester, 10 (32%) in second trimester, and 5 (16%) during third trimester. Diagnosis of ulcerative colitis (UC) was significantly more common in the POIBD group compared with the non-POIBD group (22/31, 71% vs 50/206, 24%, respectively, P < 0.001). More UC than Crohn's disease patients had active disease during pregnancy (69% vs 50%, P = 0.03, respectively). POIBD patients experienced vaginal delivery in 100% of births, compared with 164 (79.6%) in the non-POIBD group (P = 0.017). The mean gestational age at birth and the neonatal weight were similar among the study groups; 38.6 weeks and 3040 g for POIBD patients, compared with 38.7 weeks and 3055 g in the non-POIBD group. POIBD is a unique clinical entity, and the diagnosis is mostly UC. However, the maternal and neonatal outcomes are similar.

ASSOCIATION BETWEEN MATERNAL SERUM VITAMIN D AND EARLY PREGNANCY SPONTANEOUS ABORTION IN IRAQI WOMEN

Objective: This study was aimed to estimate the Vitamin D serum concentration in a cohort of women with a history of recurrent spontaneous abortion.Methods: The current cross-sectional study was conducted at Al-Diwaniya maternity and child teaching hospital, Al-Diwaniya province, Iraq. Data collection, lab work, and procedures related to the study extended from August 2016 to August 2017. The study enrolled 42 women of childbearing age who have a history of spontaneous early pregnancy loss. From each woman, a venous sample was obtained and sent to a lab to assess serum Vitamin D concentrations using standard routine biochemical methods.Results: Assessment of mean maternal serum Vitamin D concentration revealed that the mean was 21.48±11.82 (ng/ml) and the range was from 5 to 50 (ng/ml). The number of women with low serum Vitamin D (&lt;20 ng/ml) was 25 (approximately 60%), the results also revealed a highly negative correlation was obtained between number of abortions and maternal serum Vitamin D (r=−0.717, p&lt;0.001) and that the value or R2 was 0.514 which indicated that the level of Vitamin D alone can act as an independent predictor to explain 51.4% of spontaneous abortions in the participating women.Conclusion: Vitamin D level is a strong predictor of pregnancy loss in early pregnancy, and that correction of Vitamin D status among Iraqi pregnant ladies may substantially reduce the frequency of spontaneous abortion.

Association of fatty acids and lipids metabolism in placenta with early spontaneous pregnancy loss in Chinese women.

The aim of the present study was to evaluate the association of fatty acids and lipids metabolism in placenta with early spontaneous pregnancy loss (ESPL) in Chinese women. Seventy women with ESPL and 29 healthy pregnant women who asked for legal induced abortion were included in the case and control groups, respectively. The gestational age of the subject foetuses in both the case and control groups ranged from 4 to 10 weeks. The total fatty acids composition in the decidual and villous tissues was detected by gas-liquid chromatography using a standard method. Metabonomics analysis of the decidual and villous tissues was conducted by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOFMS). The total C18:3n-3 in the decidual and villous tissues, total n-3 polyunsaturated fatty acid (n-3 PUFA) in the decidual tissue, and total C18:2n-6 in the villous tissue were all significantly lower in the case group than in the control group. The ratio of C20:4n-6/C20:5n-3 in villous tissue was significantly higher, but prostaglandin I2 as well as hydroxyeicosapentaenoic acid, leukotriene B5 and thromboxane B3 in the villous tissue were significantly lower in the case group than in the control group. In addition, the low content of lysophosphatide in the decidual and villous tissues and the low content of diacylglycerol in the villous tissue were also associated with the occurance of ESPL. In conclusion, the lack of essential fatty acids, high ratio of C20:4n-6/C20:5n-3, abnormal eicosanoids metabolism and low content of lysophosphatide and diacylglycerol in the placenta were all potential risk factors for ESPL in Chinese.

Meta-analysis of the effect of the maternal vitamin D level on the risk of spontaneous pregnancy loss.

The association between vitamin D deficiency and early spontaneous pregnancy loss (SPL) is unclear. To assess the association of serum 25-hydroxyvitamin D (25(OH)D) and SPL. Embase, PubMed, and Web of Science were searched for relevant papers published before February 20, 2016, using search terms including "vitamin D" and "pregnancy loss." Case-control and cohort studies investigating the relationship of maternal serum 25(OH)D and SPL were included. Two authors independently extracted original data from the selected papers. The DerSimonian-Laird random-effects model was used to perform the meta-analysis. Heterogeneity was assessed by calculating I2 . Five studies, including 10630 pregnant women, met the inclusion criteria. There was no significant association between a low 25(OH)D level and an increased risk of SPL. In a subgroup analysis, an extremely low 25(OH)D level (<20ng/mL) was significantly associated with an increased risk of SPL in the first trimester (relative risk 2.24, 95% confidence interval 1.15-4.37); the heterogeneity across studies was not significant (I2 =0.0%, P=0.355). Severe Vitamin D deficiency could be detrimental to early embryonic development and increase the risk of early SPL.

Decreased serum vitamin D levels in early spontaneous pregnancy loss.

Background/Objectives:Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in childbearing aged women and pregnancy loss (PL) in the first trimester.Subjects/Methods:This is a cross-sectional study. Plasma was collected from 60 nulliparous women with singleton at 7–9 weeks of gestation (30 with viable gestation and 30 with PL) and 60 non-gravid childbearing aged women (30 with a successful pregnancy history, and 30 with one or more spontaneous first-trimester PL history). Quantitation of serum 25-hydroxyvitamin D (25(OH)D) and 25-hydroxyvitamin D-1 alpha hydroxylase (CYP27B1) was assayed.Results:By pregnancy/non-gravid, normal pregnant women had higher 25(OH)D (49.32 μg/l) and CYP27B1 (82.00 pg/ml) than PL women (34.49 μg/l and 37.87 pg/ml, both P<0.01); the non-gravid women with a successful pregnancy history also had higher 25(OH)D (39.56 μg/l) and CYP27B1 (39.04 pg/ml) than women with PL history (12.30 μg/l and 12.35 pg/ml, both P<0.01). The 96.7% of non-gravid women with PL history and 43.3% of PL women had serum 25(OH)D concentrations below 30 μg/l. There was a strong association between low vitamin D levels and PL (odds ratio 1.71; 95% confidence interval: 1.2–2.4, P<0.001). The regression analyses showed that PL was significantly inversely correlated with 25(OH)D (P<0.01) and CYP27B1 levels (P<0.01).Conclusions:Vitamin D deficiency associated with PL in the first trimester of pregnancy. Decreased serum vitamin D levels among childbearing aged women with the failed clinical pregnancies history may predispose to increased risk for PL.

Decidual CD56+ Natural Killer Cells in Spontaneous Early Pregnancy Loss- An Immunohistochemical Study.

Natural killer cells are believed to promote placental and trophoblastic growth and provide immune- modulation at maternal-fetal interface in pregnancy and their role in reproductive failure has been a matter of discussion. To study CD56+ Natural killer cells in spontaneous pregnancy loss. In this prospective observational study, formalin-fixed paraffin embedded sections from products of conception from twenty women each with spontaneous early pregnancy loss (test group) and elective pregnancy termination (control group). Immunohistochemical staining with CD 56 monoclonal antibody was done by avidin-biotin peroxidase technique. CD56+ cells in decidua were counted under light microscopy by two independent observers in ten high power fields (40X) and mean cell count taken. Student's paired 't'-test was used to statistically compare CD56+ NK cell population between the test and control groups. The mean number of CD56+ NK cells was higher in the decidual tissue of women who had spontaneous early pregnancy loss (mean±SD, 57.55±1.79) as compared to the mean number of CD56+ NK cells in the decidual tissue from women who underwent elective termination (mean±SD, 50.9±3.46). The difference was statistically significant (difference of 6.65 with 95% confidence interval of 4.76 to 8.54, p-value <0.0001). This could imply that CD56+ NK cells have a role in the pathogenesis of spontaneous early pregnancy loss and further large scale studies can throw more light on the mechanism and designing of appropriate therapy.

The cellular immunity and oxidative stress markers in early pregnancy loss

Objective: We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage.Material and methods: Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy.Results: Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups.Conclusion: We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.

Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis.

To determine whether an association exists between shift work and early reproductive outcomes. MEDLINE, Embase, and Web of Science were searched. Additional sources included Google Scholar, the Cochrane Library, online publications of national colleges, the ClinicalTrials.gov, and references of retrieved papers. Included studies compared female shift workers (work outside 8:00 AM to 6:00 PM) with nonshift workers with menstrual disruption (cycles less than 25 days or greater than 31 days), infertility (time-to-pregnancy exceeding 12 months), or early spontaneous pregnancy loss (less than 25 weeks). Two reviewers extracted adjusted and raw data. Random effect models were used to pool data weighting for the inverse of variance. Assessments of heterogeneity, bias, and subgroup analyses were performed. Sixteen independent cohorts from 15 studies (123,403 women) were subject to analysis. Shift workers had increased rates of menstrual disruption (16.05% [2,207/13,749] compared with 13.05% [7,561/57,932] [n=71.681, odds ratio {OR} 1.22, 95% confidence interval {CI} 1.15-1.29, I 0%]) and infertility (11.3% [529/4,668] compared with 9.9% [2,354/23,811] [OR 1.80, 95% CI 1.01-3.20, I 94%]) but not early spontaneous pregnancy loss (11.84% [939/7,931] compared with 12.11% [1,898/15,673] [n=23,604, OR 0.96, 95% CI 0.88-1.05, I 0%]). Night shifts were associated with increased early spontaneous pregnancy loss (n=13,018, OR 1.29, 95% CI 1.11-1.50, I 0%). Confounder adjustment led to persistent relationships between shift work and menstrual disruption (adjusted OR 1.15, 95% CI 1.01-1.31, I 70%) but not infertility (adjusted OR 1.11 95% CI 0.86-1.44, I 61%). The association between night shifts and early spontaneous pregnancy loss remained (adjusted OR 1.41 95% CI 1.22-1.63, I 0%). This review provides evidence for an association between performing shift work and early reproductive outcomes, consistent with later pregnancy findings. However, there is currently insufficient evidence for clinicians to advise restricting shift work in women of reproductive age.

Placental Expression of CD100, CD72 and CD45 Is Dysregulated in Human Miscarriage

Context and ObjectiveThe etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques.PatientsPlacenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8th and 12th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38–40 weeks of gestation was also studied.ResultsCD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples.ConclusionsFetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

Possible role of placental CD100, CD72 and CD45 molecules in human miscarriage

The precise mechanism for recurrent miscarriage is unclear. A lot of metabolic alterations are involved in the missed intercommunication between mother and its foetus, causing their reciprocal intolerance. The identification of new molecules involved in pregnancy loss represents the main objective of our study. We analysed the semaphorin CD100, its natural receptor CD72 and the glycoprotein CD45, physically and functionally associated to CD100 in the placental tissues from recurrent miscarriages by real-time PCR, western blotting and immunohistochemistry. Placental tissue was obtained during surgical uterine evacuation in 72 caucasian women with early spontaneous pregnancy loss between 8th and 12th week of gestation and classified in four groups defined as first, second, third and fourth miscarriages. Other two normal placental groups were recruited: a) first trimester placentas (n = 18), matched for gestational age with placentas from spontaneous pregnancy loss; b) third trimester placentas (n = 6) at 38-40 weeks of gestation. We demonstrated that CD72, CD45 and CD100 mRNA were detectable in placental tissues with different expression in normal and pathological conditions. In addition, we demonstrated that CD72 and CD45 molecules were expressed in foetal macrophages and that their protein levels were especially deregulated in first and second miscarriages at about 10 weeks of gestation. On the contrary, CD100 cleaved protein appeared to be absent in placenta. In conclusion, our findings underline a possible role for CD100, CD72 and CD45 molecules in recurrent miscarriages, showing an important foetal involvement in the occurring of pregnancy loss.

P02.06: Decidua basalis in spontaneous early pregnancy loss

P02.06: Decidua basalis in spontaneous early pregnancy loss