Caring for Women in an Active War Zone.

Emergency nursing in Gaza's war zone presents innumerable challenges when caring for female patients in a depleted health care system. Negative health outcomes specifically impact women of all ages due to lack of access to menstrual products, prenatal and primary care, private bathrooms, medication, essential nutrition, and clean water. The massive destruction of infrastructure and consequent internal displacement of millions has led to a rise in infectious diseases. The few remaining functional hospitals depend heavily on foreign medical delegations for supplies, which results in a lack of standardized treatment for women's health complaints. Emergency departments must also navigate overcrowding, lack of basic supplies and specialists, and prioritization of daily mass casualty incidents from nearby explosions. These obstacles make treatment, discharge teaching, and follow-up care for women's health difficult to implement. Despite these arduous circumstances, Gazan health care professionals find innovative solutions to improve outcomes and reduce harm while honoring the cultural and religious preferences of their female patients.

Genetic landscape of thrombophilia in recurrent miscarriages.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and well-designed multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

Lupus pregnancy outcomes in women with previous adverse outcomes: a prospective cohort study.

OBJECTIVES: The primary objective of this prospective cohort study was to assess the usefulness of a predefined multidisciplinary care pathway-based management on pregnancy outcome(s) in women with SLE who already had at least one adverse obstetric outcome(s). METHODS: Between March 2010 and March 2023, all consecutive, consenting women with SLE who already had at least one previous adverse obstetric outcome (preterm labour, pre-eclampsia, termination of pregnancy, miscarriage, intrauterine growth retardation (IUGR), preterm birth, low birth weight (LBW), intrauterine death (IUD) or stillbirth] were prospectively screened and counselled. The protocol comprised preconception and post-natal drug and disease status review, periodic ante-natal visits for the monitoring of pregnancy and drug and disease status review and post-natal drug and disease status review and contraception advice. Therapeutic changes were made as necessary at each visit. RESULTS: A total of 213 women were screened and 197 women (age, 28 ± 6.34 years) were enrolled who had 226 pregnancies. Previous poor obstetric outcomes were miscarriage(s), 186; termination of pregnancy, 4; preterm labour, 51; IUGR, 36; IUD or stillbirth, 16; low birth weight (LBW), 44 and pre-eclampsia, 4. Seventy-seven (39%) women had secondary APS and 37 (19%) had a history of lupus nephritis. There were 194/226 (86%) live births [40 LBW (18%); caesarean section in 101 (45%)]. Thirty pregnancies culminated in miscarriages and 2 in IUDs (14%). Sixty-eight patients (30%) experienced lupus flare during pregnancy (36 mild, 20 moderate and 8 severe). CONCLUSION: Our experience underscores the usefulness of a predefined multidisciplinary care pathway-based management for improving pregnancy outcomes in women with SLE who had previous adverse outcomes. Key Points • In women with SLE who had previous adverse obstetric outcome(s) a risk of poor outcome in subsequent pregnancy remains. • Good pregnancy outcomes in these women could be achieved by predefined  multidisciplinary care pathways focussed on addressing all relevant issues. • Improved access to rheumatology services and collaboration between rheumatologists and obstetricians is key to improving outcomes in SLE pregnancies.

Mosaicism for Autosomal Trisomies: A Comprehensive Analysis of 1266 Published Cases Focusing on Maternal Age and Reproductive History.

Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Cytogenetic abnormalities associated with reproductive failure in Pakistani population: Experience of a tertiary care hospital.

Constitutional chromosomal abnormalities play a significant role in causing reproductive anomalies in individuals of reproductive age. With the rapid advancement of genome engineering techniques, it has now become possible to cure different genetic disorders. However, very limited data is available regarding the prevalence of such aberrations in the Pakistani population. Considering this factor, this retrospective analysis was undertaken to elucidate the type and prevalence rate of such abnormalities in our population. A total of 241 individuals, who were referred to the Liaquat National Hospital, from January 2017 to December 2021, with a history of infertility or miscarriages, were evaluated using the standard GTG banding technique. The results revealed a notably high percentage 44(18.2%) of chromosomal abnormalities in our population. Surprisingly, the frequency of these anomalies was observed to be higher in males than in females. However, further research is needed using a larger sample size to confirm the findings of this investigation.

The obstetrical consequences of ischemic stroke in women of childbearing age.

PURPOSE: Although recurrence risk is a major concern for women having had an ischemic stroke (IS) and who are planning a pregnancy, studies on recurrence risk and pregnancy outcomes are scarce and heterogeneous. METHODS: This retrospective study assessed women aged 15-44 years with a diagnosis of ischemic stroke admitted in the Lyon Stroke Centre, France, between January 2009 and December 2013. The primary outcome was stroke recurrence during pregnancy or the post-partum period. Secondary outcomes were pregnancy complications. RESULTS: Overall, 104 women with a prior ischemic stroke were included. Mean age at the time of the stroke was 36 ± 6.7 years old. Stroke etiology was large-artery atherosclerosis for 1 woman, cardioembolism for 23 women, and undetermined for 55 women. No antiphospholipid syndrome was found. Among them, 29 women had 58 subsequent pregnancies. Overall, there were three IS recurrence (2.9%), but none occurred during pregnancy. There were 27 miscarriages (47% of pregnancies), two pre-eclampsia (3%), and one stillbirth (1.7%). CONCLUSIONS: We observed no recurrence of IS during pregnancy. The study also highlighted that the risk of miscarriages was higher than general population and that of stillbirth should be further studied.

Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology.

Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.

Antiphospholipid syndrome pathogenesis in 2023: an update of new mechanisms or just a reconsideration of the old ones?

Antibodies against phospholipid (aPL)-binding proteins, in particular, beta 2 glycoprotein I (ß2GPI), are diagnostic/classification and pathogenic antibodies in antiphospholipid syndrome (APS). ß2GPI-aPL recognize their target on endothelium and trigger a pro-thrombotic phenotype which is amplified by circulating monocytes, platelets and neutrophils. Complement activation is required as supported by the lack of aPL-mediated effects in animal models when the complement cascade is blocked. The final result is a localized clot. A strong generalized inflammatory response is associated with catastrophic APS, the clinical variant characterized by systemic thrombotic microangiopathy. A two-hit hypothesis was suggested to explain why persistent aPL are associated with acute events only when a second hit allows antibody/complement binding by modulating ß2GPI tissue presentation. ß2GPI/ß2GPI-aPL are also responsible for obstetric APS, being the molecule physiologically present in placental/decidual tissues. Additional mechanisms mediated by aPL with different characteristics have been reported, but their diagnostic/prognostic value is still a matter of research.

The integration and implications of artificial intelligence in forensic science.

This commentary explores the integration of artificial intelligence (AI) in forensic science and its potential implications. The applications of AI in forensic disciplines such as medicine, forensic anthropology, digital forensics, and taphonomy have enhanced the accuracy and efficiency of identification processes and the analysis of digital evidence. However, this rapid advancement prompts critical considerations in privacy, data protection, bias and fairness, and the accuracy and reliability of AI systems. The inherent challenges of the "black box" nature of AI algorithms call for transparency and accountability to maintain trust and uphold the integrity of forensic investigations. Ethical use, legal compliance, interdisciplinary collaboration, education, data integrity, standardization, human oversight, and societal impact, along with sustainability are identified as pivotal areas requiring urgent attention. The discussion underscores the need for rigorous scrutiny, standardized operating procedures, and proactive dialogue to ensure the responsible advancement of AI in forensic science.

Do elevated thyrotropin levels increase the risk of miscarriages: yes or no?

BACKGROUND: To examine correlation between elevated levels of thyrotropin with the frequency of miscarriages. METHODS: A cross-sectional study was conducted on the 380 respondents and it investigated TSH (thyrotropin), thyroid peroxidase antibody(anti-TPO) and free thyroxine (FT4) in pregnant women who had a miscarriage (N = 179) and pregnant women with normal pregnancies (N = 201). RESULTS: The incidence of subclinical hypothyroidism in the miscarriages group was higher than in control group (61.4% vrs 15.79% (p < 0.001). In the miscarriages group with hypothyroidism (first trimester) mean value of TSH was significantly higher 4.31 ± 2.55 mIU/L compared to the control group 1.95 ± 0.86mIU/L (p < 0.001). Logistic multivariate regression revealed that TSH and body mass index (BMI) have a significant influence on the miscarriage; TSH level has a higher odds ratio (OR) 1.47 CI (95% 1.22-1.78) than BMI (OR) 1.14 CI (95% 1.06-1.23)) (p < 0.001). The combination of thyroid autoimmunity and TSH > 2.5mIU/L increase the risk of miscarriage (65.75%) compared to positive anti-TPO antibodies and TSH < 2.5mIU/L(14.15%)(p < 0.001). CONCLUSIONS: Higher TSH levels correspond with obesity during early pregnancy and may be a sign of maternal thyroid dysfunction. Physiological thyroid function in the first trimester of pregnancy is important for perinatal outcome.

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Immunological effects of anti-coagulant unfractionated heparin in pregnant Chinese women with cryptic recurrent miscarriages.

Introduction: Anti-coagulant unfractionated heparin of low molecular weight (ACUHlmw) therapy is popularly practised in the therapy of recurrent miscarriages (RMC) due to its anti-coagulant properties. However, several in vitro investigations have hypothesized about the possible immunological effects of ACUHlmw. Material and methods: We examined pregnant women with cryptic RMC (cRMC) to determine whether ACUHlmw could regulate the immune reaction in vivo during their pregnancy. In this study, a total of 51 women were subjected to tinzaparin and 48 patients were considered as control women on the basis of an open single-centre randomized controlled trial. During different fertilization weeks (FW) 7, 19, 29, and 35 plasma samples were acquired for eleven chemokine and cytokine levels and then investigated by multiplex bead technology and selected to portray T-helper subset-related immunity. Results: We did not find any difference in chemokine C-C motif ligand-2, -17, -22, chemokine C-X-C motif ligand-1, -8, -12, -13 or cytokine interleukin-6 when a mixed linear model test was carried out on ACUHlmw in both the study and control women. However, differences were observed in the mixed linear model test on ACUHlmw in both the study and control women during pregnancy of the Th1/Th17 related chemokine C-X-C motif ligand-10 (p = 0.01), -11 (p < 0.001) and chemokine C-C motif ligand-20 (p = 0.04) respectively. Conclusions: A positive outcome of ACUHlmw therapy in vivo was observed, thus establishing its potential proinflammatory effect. During 2nd and 3rd trimesters, the observed harmonious enlargement in Th1/Th17 related chemokine and cytokine levels does not recommend a fruitful immunological impact of ACUHlmw therapy in vivo.

[Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages].

OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-ß2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION: Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Platelet Glycoprotein Receptor Ia-C807T and IIIa-PlA1/PlA2 Genetic Polymorphisms Are Associated With Enhanced Platelet Function in Women With Recurrent Miscarriages.

INTRODUCTION: Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages. METHODS: This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100. RESULTS:  In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds; relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean: 121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the median and OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. CONCLUSION: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promote the analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

miR604A>G gene polymorphism is associated with recurrent pregnancy loss in Turkish women

SUMMARY OBJECTIVE: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population. METHODS: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied. RESULTS: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively). CONCLUSION: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

The impact of the COVID-19 pandemic on the course of miscarriages.

OBJECTIVES: Miscarriage is the most common complication of pregnancy. Infections are well-known causes of pregnancy loss. It has been suggested that infection with SARS-CoV-2 virus may also have an adverse effect on the course of early pregnancy, causing miscarriage. AIM: To assess the impact of the COVID-19 pandemic on pregnancy loss during the first half of pregnancy. MATERIAL AND METHODS: The clinical records of patients hospitalized at the Department of Fetal Medicine and Gynecology; Medical University of Lodz were retrospectively reviewed. The study was done during the pandemic (March 2020 to the end of March 2022) and the previous 2 years due to missed abortion, indicated by no fetal heartbeat and spontaneous (complete or incomplete) abortion with vaginal bleeding. RESULTS: While 682 women were hospitalized due to miscarriage in the first half of pregnancy in the period 2018-2020, there were 516 hospitalized during the pandemic. No differences in the proportion of missed and spontaneous abortions with bleeding were found between the group of patients before and during the epidemic SARS CoV-2. COVID-19 exposure appears to have an impact on earlier pregnancy loss. CONCLUSIONS: There is no evidence that the COVID-19 pandemic predisposes to the abnormal course of pregnancy in its first half. OBJECTIVES: Miscarriage is the most common complication of pregnancy. Infections are well-known causes of pregnancy loss. It has been suggested that infection with SARS-CoV-2 virus may also have an adverse effect on the course of early pregnancy, causing miscarriage. AIM: To assess the impact of the COVID-19 pandemic on pregnancy loss during the first half of pregnancy. MATERIAL AND METHODS: The clinical records of patients hospitalized at the Department of Fetal Medicine and Gynecology; Medical University of Lodz were retrospectively reviewed. The study was done during the pandemic (March 2020 to the end of March 2022) and the previous 2 years due to missed abortion, indicated by no fetal heartbeat and spontaneous (complete or incomplete) abortion with vaginal bleeding. RESULTS: While 682 women were hospitalized due to miscarriage in the first half of pregnancy in the period 2018-2020, there were 516 hospitalized during the pandemic. No differences in the proportion of missed and spontaneous abortions with bleeding were found between the group of patients before and during the epidemic SARS CoV-2. COVID-19 exposure appears to have an impact on earlier pregnancy loss. CONCLUSIONS: There is no evidence that the COVID-19 pandemic predisposes to the abnormal course of pregnancy in its first half.

Vitamin D Status in Women with a History of Infertility and Decreased Fecundability: A Population-Based Study.

BACKGROUND: Infertility and fecundability problems have been linked with lower 25-hydroxyvitamin D (25(OH)D) concentrations, but studies conducted with small, heterogenous or selected populations have shown inconsistent results. METHODS: This study included women at age 31 from prospective population-based Northern Finland Birth Cohort 1966. Serum 25(OH)D concentrations were evaluated between women with or without previous infertility examinations or treatments (infertility group, n = 375, reference group, n = 2051) and time to pregnancy (TTP) of over 12 months (decreased fecundability group, n = 338) with a wide range of confounders. Furthermore, 25(OH)D concentrations were also compared among reproductive outcomes. RESULTS: The mean 25(OH)D concentration was lower and 25(OH)D < 30 nmol/L was more frequent in women with a history of infertility compared to reference group. Moreover, 25(OH)D > 75 nmol/L was more frequent in the reference group. The mean 25(OH)D concentration was lower in women who had had multiple miscarriages. Both history of infertility (ß = -2.7, 95% confidence interval (CI) -4.6, -0.7) and decreased fecundability associated with lower 25(OH)D concentration (ß = -4.1, 95% CI -7.4, -0.8) after adjustments. In conclusion, this population-based study demonstrated that previous infertility and decreased fecundability were associated with lower 25(OH)D.

Insight into the 8p23.1 duplication syndrome: Case report of a young women with infertility.

Objective: To report the case of a young woman with repeated conception failure, whose karyotype showed an unbalanced complex chromosomal rearrangement involving a large duplication harboring >115 genes and overlapping the 8p23.1 duplication syndrome region. The 8p23.1 duplication syndrome results from a tandem duplication on the short arm of chromosome 8 containing the 4 genes (GATA4, TNKS, SOX7, XKR6) responsible for the most common phenotypic features: developmental delay/learning disabilities, congenital heart disease and dysmorphism. Design: Case report and review of the literature. Setting: American University of Beirut Medical Center, department of Pathology and Laboratory medicine.Patient(s): Young woman referred to the genetic clinics for the workup of secondary idiopathic infertility with multiple unsuccessful inseminations and in vitro fertilizations. Interventions: Peripheral blood karyotype analysis from the patient and her parents. Elucidation of the CCR required whole chromosome painting Fluorescent in Situ Hybridization and Chromosomal Microarray. Main outcome measures: The few published reports on 8p23.1 duplication syndrome (<50 cases) describing carriers reveal a wide range of phenotypic consequences with heterogeneous severity. The main outcome is to further understand this syndrome. Results: Chromosomal microarray analysis detected a large (12Mb) pathogenic Copy Number Variant (CNV) at 8p23.3p23.1, overlapping the 8p23.1 duplication syndrome region. This CNV, classified as pathogenic, was shown to carry little significance in our patient. Conclusions: 8p23.1 duplication syndrome display a variable expressivity, ranging from overt syndromic features to minimal effect on the phenotype as shown in this case. Interpretation of prenatal detection of 8p23.1 duplication especially in preimplantation diagnosis is thus challenging. Nevertheless, this case emphasizes the importance of genetic testing in infertile patients displaying a normal phenotype.

Perinatal outcomes in nulliparous women with a history of multiple pregnancy losses according to number of previous pregnancy losses.

BACKGROUND: While it is widely acknowledged that pregnancy losses can lead to negative outcomes for both mothers and fetuses, there is limited information available on the specific levels of risk associated with each additional pregnancy loss. OBJECTIVE: This study aimed to investigate the effect of number of previous pregnancy losses among nulliparous women on maternal and neonatal adverse outcomes. STUDY DESIGN: This was a multicenter retrospective cohort study. The study population included all nulliparous women with singleton pregnancies who delivered in all university-affiliated obstetrical centers in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who delivered at our medical centers and had varying numbers of previous pregnancy losses were compared with women who had no previous pregnancy loss. The primary outcome of this study was preterm delivery rate at <37 weeks of gestation. The secondary outcomes were adverse maternal and neonatal outcomes. Univariate analysis was performed using multiple logistic regression modeling. RESULTS: During the study period, 97,904 nulliparous women met the inclusion and exclusion criteria. Of those women, 84,245 (86%) had no previous pregnancy losses (reference group), 10,724 (11%) had 1 previous pregnancy loss, 2150 (2.2%) had 2 previous pregnancy losses, 516 (0.5%) had 3 previous pregnancy losses, 160 (0.2%) had 4 previous pregnancy losses, and 99 (0.1%) had ≥5 previous pregnancy losses. Women who had previous pregnancy losses had significantly higher rates of preterm delivery, hypertensive disorders of pregnancy, diabetes mellitus (pregestational and gestational), unplanned cesarean delivery, perinatal death, neonatal intensive care unit admissions, and neonatal hypoglycemia. The risks of preterm delivery and most other adverse obstetrical outcomes correlated with the number of previous pregnancy losses. Multivariate analyses showed that each previous pregnancy loss was associated with an additional, significant, increased risk of preterm delivery of 14% at <37 weeks of gestation, 37% at <34 weeks of gestation, 45% at <32 weeks of gestation, and 77% at <28 weeks of gestation. CONCLUSION: A history of previous pregnancy losses increased the risk of preterm delivery and other perinatal outcomes in a dose-dependent manner. To minimize perinatal complications, obstetricians should be aware of the risks and complications in this unique population, consider close monitoring of the cervical length, and maintain high vigilance in case of complications with special attention to other potentially modifiable risks.