Higher Risk Of Pregnancy Loss Research Articles

Mechanical and bioprosthetic valves in young women: a systematic review and meta-analysis of cardiac, maternal, and fetal outcomes

Valve replacement for the heart in young women, particularly those who are pregnant, is challenging. It requires finding the right balance between valve durability, managing anticoagulation, and ensuring positive reproductive outcomes. This systematic review and meta-analysis compared mechanical prosthetic (MP) and bioprosthetic valves (BP) across cardiac, maternal, and fetal outcomes. Nine studies were included following a comprehensive literature search. The analysis revealed MACE involving MP and BP were not significantly different (OR: 1.31, 95% CI: 0.82–2.09, p = 0.26). Thromboembolic events were significantly more frequent in the MP group (OR: 6.59, 95% CI: 3.41–12.74, p < 0.001), while structural valve deterioration (SVD) occurred more often in BP recipients (OR: 0.01, 95% CI: 0.00–0.70, p = 0.03). Maternal outcomes showed a higher risk of pregnancy loss in MP recipients (OR: 4.62, 95% CI: 1.87–11.40, p < 0.001). Preterm delivery was more common went down in the MP group, but it wasn't enough to warrant statistical analysis (OR: 2.20, 95% CI: 0.86–5.58, p = 0.10). For reoperation or redo surgery, MP had lower risk and showed superior results than BP (OR: 0.06, 95% CI: 0.01–0.32, p = 0.001). These findings highlight the complexities involved in choosing between valve types. Although MP valves last longer, they increase the likelihood of thromboembolic events and miscarriage. While improving results for both the mother and the unborn child, BP valves, are prone to structural deterioration, necessitating reoperation. Individualized treatment decisions that consider patient preferences, clinical context, and reproductive plans are essential to optimizing outcomes for young women requiring valve replacement.

The predictive value of ultrasound markers for pregnancy outcomes in recurrent pregnancy loss: a retrospective study

Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG < 69,636.6 mIU/ml was associated with a higher risk of pregnancy loss in the seventh gestation week. An mGSD < 18.3 mm, adjusted for age, BMI, and previous pregnancy loss in the sixth week, was linked to an increased risk of first trimester pregnancy loss. A small CRL measurement (less than 2.4 mm, 9.9 mm, 16.9 mm, and 18.6 mm) in the sixth, seventh, eighth and ninth week was closely correlated with higher risk of first trimester pregnancy loss. Furthermore, an mGSD < 33.3 mm and > 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

O-315 Familial endocrine disease increases the risk of pregnancy loss and recurrent pregnancy loss– a nationwide register-based study of 366,548 Danish women

Abstract Study question Is endocrine disease and pregnancy loss associated, and can the association be due to inherited genetic causes? Summary answer Endocrine disease is associated with an increasing number of pregnancy losses. Endocrine disease in parents and siblings increases a woman’s risk of pregnancy loss. What is known already One in four pregnancies results in a pregnancy loss, but only 60% hereof are due to detectable chromosome abnormalities. The remaining 40% are suspected to be caused by other factors such as maternal comorbidity. Recurrent pregnancy loss (RPL) is defined as 2 or 3 consecutive losses and affects 1-3% of couples trying to conceive. Pregnancy loss has been associated with endocrine diseases, e.g., thyroid disease, diabetes, or PCOS. Furthermore, thyroid autoimmunity has been associated with RPL. It is unknown if other endocrine diseases are associated with RPL. To date, there is no evidence for a genetic basis of the risk. Study design, size, duration Danish nationwide cohort study including data from the Danish National Health Registers on ICD-8/ICD-10 diagnosis codes, all pregnancy outcomes and redeemed medicine prescriptions. Endocrine disease was defined as any endocrine disease (e.g., diabetes, thyroid disease, PCOS etc.). The study included in total 366,548 women, including 54,394 women with endocrine disease and 312,154 without endocrine diseases. The study included data from 1973 to 2022. Linkage to parent and siblings was available through the Multi-Generation Registry Lite. Participants/materials, setting, methods The cohort consisted of women born between 1977-1993 with ≥1 pregnancy. The exposure was endocrine disease. Logistic regression models adjusted for birth year provided odds ratios (ORs) for endocrine diseases according to number of pregnancy losses. Parent-offspring and sibling regression provided estimates for familial aggregation, assessing the degree of resemblance between relatives to infer the potential influence of shared familial factors. The variance-covariance matrix was adjusted using the Huber-White method to account for familial clustering. Main results and the role of chance We found a significant association between endocrine disease and pregnancy loss increasing with the number of pregnancy losses; OR and 95%CI for one loss 1.15 (1.12-1.17), two losses 1.31 (1.24-1.38) and ≥ three losses 1.81 (1.70-1.93). Further, endocrine disease was associated with RPL (OR 1.87, (1.74-2.00)). The association was strongest with primary RPL (OR 2.13 (1.94-2.35)), compared to secondary RPL (OR 1.58 (1.42-1.76)). In cases where either of a woman’s parents was diagnosed with an endocrine disease, she also had a higher risk of pregnancy loss (OR 1.06 (1.04–1.08)) and RPL (OR 1.07 (1.01–1.14)), compared to a woman with parents without endocrine disease. If a woman’s sibling had an endocrine disease, the OR for pregnancy loss was 1.07 (1.03–1.11) and RPL 1.17 (1.03–1.33). Further stratification into individual endocrine phenotypes revealed that type 2 diabetes conferred a comparable risk: for offspring of parents with this condition, the risk of pregnancy loss increased to an OR of 1.08 (1.06–1.11), and for siblings, the OR was 1.13 (1.02–1.25). This effect persisted even when adjusting for the disease in the individual experiencing the loss. Limitations, reasons for caution Very early pregnancy losses are often not handled at the hospital and therefore not part of the Danish registers. Thus, there is a risk of underdiagnosed pregnancy losses, although this would be the case for both the exposed and control cohort. Wider implications of the findings Women with RPL should be investigated for endocrine disease, and family history of endocrine disease is an important and novel risk factor that should guide the diagnostic work-up. Identifying the shared mechanism or pleiotropic effects between pregnancy loss and endocrine disease should be a focus area. Trial registration number Research related to this project was supported by the Novo Nordisk Foundation (ID: NNF22OC0077221, NNF23OC0087269) and the William Demant Foundation (salary for Pia Egerup).

O-313 Increased risk of preterm deliveries in long term survivors of children, adolescent, and young adult exposure to chemotherapy or chemo-radiotherapy: a systematic review and meta-analysis

Abstract Study question What is the long-term impact on pregnancy outcomes of a childhood adolescent, and young adult (AYA) exposure to chemotherapy or chemo-radiotherapy? Summary answer Whereas preterm delivery and pregnancy loss were significantly increased in chemotherapy and chemo-radiotherapy groups compared to control group, live birth rate was not affected. What is known already The impact of radiotherapy on the uterus has been widely described. Lately, studies have underlined the potential negative effect of chemotherapy on the womb. Indeed, three recent publications have reported that adult females treated with hematopoietic stem cell transplantation (HSCT) in childhood had a reduced uterus volume, both after conditioning by total body irradiation (TBI) and after alkylating agents-based regimen. The pregnancy outcome will depend in part on the uterine volume and its vascularization. Therefore, a history of chemotherapy or chemo-radiotherapy may be associated to an increased risk of obstetrical complications. Study design, size, duration A systematic review and meta-analysis were performed on comparative studies. Searches were conducted on Medline, Embase and the Cochrane Library from 1990 to April 2023, using the main following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, pregnancy outcome, pregnancy complications, preterm delivery, and pregnancy loss. All studies reporting live birth rate (LBR) in adult females who have received chemotherapy and/or chemo-radiotherapy during childhood and AYA &amp;lt; 25 years were included. Participants/materials, setting, methods Two independent reviewers carried out the study selection, the bias assessment using the ROBINS-I tool and data extraction. The primary outcome was the LBR. The main secondary outcomes were preterm delivery and pregnancy loss rates. For each outcome, a random-effect frequentist network meta-analysis (NMA) was carried out to estimate risk ratios with their 95% confidence intervals. Sensitivity analyses were conducted by excluding studies at high risk of bias and leave-one out method. Main results and the role of chance After reviewing 2,328 abstracts, 25 studies were retained for review. Eight studies were included in the meta-analysis on LBR: 3,997 females became pregnant leading to 2,878 live births. The NMA shows a moderate heterogeneity/inconsistency (τ²= 0.012, I²=58% [11%; 80%]) and did not show any significant impact of treatments on LBR. Sensitivity analyses lead to the same conclusions. Six studies reported a total of 125 preterm deliveries out of 1,976 started pregnancies and were included in the NMA (τ²= 0.07, I²=19% [0%; 62%]). Chemo-radiotherapy was significantly associated with higher risk of preterm delivery compared to the control group (3.44 [1.94; 6.09]) and chemotherapy group (1.93 [1.19; 3.15]). The chemotherapy group was associated with a statistically higher risk of preterm delivery than the control group (1.78 [1.01; 3.13]). Eight studies including 606 pregnancy loss out of 3,653 started pregnancies were entered in the NMA (τ²= 0, I²=0% [0%; 65%]). Chemo-radiotherapy was associated with significantly higher risk of pregnancy loss compared to the control group (1.80 [1.34; 2.43]) and chemotherapy group (1.68 [1.26; 2.25]). No statistical difference was shown in the risk of pregnancy loss between the chemotherapy and the control groups (1.07 [0.87; 1.32]). Limitations, reasons for caution Study selection was focused on live birth rate; therefore, the research was probably not exhaustive for the secondary outcomes. Adjustment on parity or history of hormonal replacement therapy (HRT) was not performed because of a lack of data. Subgroup analysis on the type of chemotherapy was not possible. Wider implications of the findings This meta-analysis reports a negative impact of chemotherapy or chemo-radiotherapy on obstetric outcomes. Further studies including clear information on parity and use of HRT are needed. Moreover, a description on the type of chemotherapy could help to refine these conclusions. Trial registration number Not applicable

Job loss during pregnancy and the risk of miscarriage and stillbirth.

Does the exposure to job loss during pregnancy increase the risk of miscarriage or stillbirth? The experience of own or partner's job loss during the pregnancy is associated with an increased risk of miscarriageand stillbirth. Prior research on the psycho-social aspect of pregnancy loss has investigated the contextual and the individual-level stressors. At the contextual level, natural disasters, air pollution, and economic downturns are associated with higher risk of pregnancy loss. At the individual level, intense working schedules and financial strain are linked with increased risk of pregnancy loss both at early and later stages of the gestation. This work draws on high-quality individual data of 'Understanding Society', a longitudinal survey that has interviewed a representative sample of households living in the UK annually since 2009. Approximately 40000 households were recruited. The analyses use all the available survey waves (1-12, 2009-2022). The final sample consisted of 8142 pregnancy episodes that contain complete informationon pregnancy outcome and date of conception. Ongoing pregnancies at the time of the interview were excluded from the final sample. The outcome variable indicated whether a pregnancy resulted in a live birth or a pregnancy loss whereas the exposure variable identified the women's or their partner's job loss because of redundancy or a dismissal. Logistic regression models were employed to estimate the relation between job loss during pregnancy and pregnancy loss. The models were adjusted for an array of socio-demographic and economic characteristics following a stepwise approach. Several sensitivity analyses complemented the main findings. Baseline models controlling for women's demographic background and prior experience of miscarriage estimated an increased risk of pregnancy loss when women were exposed to their own or their partner's job loss during their pregnancy (odds ratio (OR) = 1.99, 95% CI: 1.32, 2.99). When the models were adjusted for all socio-economic and partnership-related covariates the association remained robust (OR = 1.81, 95% CI: 1.20, 2.73). First, the pregnancy outcome and the date of conception were self-reported and may besubjected to recall and social desirability bias. Second, although we adjusted for an array socio-demographic characteristics and self-reported health, other contextual factors might be correlated with both job loss and pregnancy loss. Third, owing to the limited sample size, we could not assess if the main finding holds across different socio-economic strata. By showing that exposure to a job loss during pregnancy increases the risk of miscarriage and stillbirth, we underline the relevance of pregnancy loss as a preventable public health matter. This result also calls for policy designthat enhances labour market protection and social security buffers for pregnant women and their partners. The authors received the following financial support for the research, authorship, and/or publication of this article: H2020 Excellent Science, H2020 European Research Council, Grant/Award Number: 694262 (project DisCont-Discontinuities in Household and Family Formation) and the Economic and Social Research Centre on Micro-Social Change (MiSoC). There are no conflicts of interest to declare.

Clinical and laboratory parameters associated with cycle outcomes in patients undergoing euploid frozen blastocyst transfer

Research questionWhich factors impact on clinical pregnancy rate (CPR) and live birth rates (LBR) in euploid frozen embryo transfer (eFET) cycles? DesignRetrospective observational study including 1660 eFET cycles with 2439 euploid blastocysts, from November 2016 to December 2020. The impact of clinical and laboratory parameters on CPR, biochemical miscarriage rate (BMR), clinical miscarriage rate (CMR) and LBR was evaluated. ResultsCPR per transfer was 63.4%, LBR per transfer 51.6%. CPR and LBR were significantly higher when double embryo transfer (DET) was performed (71.6% versus 57.7%, P < 0.001; 55.2% versus 49.1%, P = 0.016, respectively). However, pregnancy loss was significantly higher in the DET group (28.8% versus 22.8%, P = 0.02). When patients were classified by body mass index (BMI), no differences were observed for CPR, but CMR was lower (P < 0.001) and LBR higher (p = 0.031) for the normal BMI group. The natural cycle protocol revealed lower CMR (P < 0.001) and lower pregnancy loss (P < 0.001); subsequently, higher LBR (57.6%, 48.8%, 45.0%, P = 0.001) compared with hormonal replacement protocol and stimulated cycle. Day of trophectoderm biopsy affected CPR (P < 0.001) and LBR (P < 0.001), yet no differences were observed for BMR, CMR or pregnancy loss. The multivariate analysis showed that day 6/7 embryos had lower probabilities for pregnancy; overweight and obesity had a negative impact on LBR, and natural cycle improved LBR (adjusted odds ratio 1.445, 95% confidence interval 0.519–0.806). ConclusionsDay of biopsy affected CPR, while BMI and endometrial preparation protocol were associated with LBR in eFET. DET should be discouraged as it will increase the risk of pregnancy loss. Women with higher BMI should be aware of the higher risk of pregnancy loss and lower LBR even though a euploid blastocyst is transferred.

Risk of adverse pregnancy outcomes by maternal occupational status: A national population-based study in South Korea.

This study examined the association between maternal occupational status and adverse pregnancy outcomes in the general South Korean population. We analyzed 1825 845 employed and non-employed women with a diagnostic code for pregnancy in the National Health Insurance Service (NHIS) database (2010-2019) of South Korea. Based on their employment status and type of occupation, we calculated risk ratios for three adverse outcomes: early abortive outcomes (miscarriage, ectopic pregnancy, and molar pregnancy), stillbirth, and no live birth (diagnosis of pregnancy with no record of live birth thereafter, which include early abortive outcomes and stillbirth) with adjusting for covariates. Overall, 18.0%, 0.7%, and 39.8% ended in early abortive outcomes, stillbirths, and no live births, respectively. The risk of early abortive outcomes and stillbirths was higher in non-employed women than in employed women, while no live births were more frequent in employed women. Those in the health and social work industry showed the highest risk of no live births. Manufacturing jobs (1.030, 95% CI: 1.013, 1.047) and health/social work (1.029, 95% CI: 1.012, 1.046) were associated with an increased risk of early abortive outcomes compared with financial and insurance jobs. Consistently higher risks of no live births were observed in the manufacturing, wholesale/retail trade, education, health/social work, and public/social/personal service occupation. Employment during pregnancy and several occupation types were associated with a higher risk of pregnancy loss. Additional research using detailed job activity data is needed to determine specific occupational causes of adverse pregnancy outcomes.

Achievement of a 136-day delayed-interval delivery of a second twin with minimum intervention

The rate of multiple pregnancies in the past three decades has increased dramatically. Twin pregnancies have a higher risk of pregnancy loss owing to premature birth. Although the premature delivery of the first twin is usually followed by spontaneous birth of the second twin, there are ways to delay the delivery of the second twin to enhance survival and neonatal outcomes. However, there is insufficient evidence to support the role of any interventions such as cerclage, hospitalization, tocolytics, and/or antibiotics. As a result, the management of delayed interval for the delivery of the second twin varies depending on each case. The purpose of this study was to report the obstetric components of a successful delayed-interval delivery, with an emphasis on the current conflicts around the active management of the delayed interval delivery of the second twin. A case of a 40-year-old, G5P4, woman who had three cesarean sections is presented. She got pregnant with a dichorionic diamniotic twin. At 17 weeks of gestation, she developed sudden severe lower abdominal pain, vaginal bleeding, and spontaneous expulsion of the first fetus weighing 179 g. After delivery of the first twin, the vaginal bleeding became minimal, and the cervix was reconstituted soon, so cervical cerclage was not offered. The umbilical cord of the first fetus was cut at the level of the external cervical os, and the placenta was retained. She received intravenous fluids, anti-D prophylaxis, paracetamol, and antibiotics. The patient was keen to continue with the pregnancy and was informed about the risks and benefits. The management was mainly an outpatient basis after an initial short hospital stay of 6 days before being discharged (upon her request); during the follow-up, she did not develop any clinical manifestations of maternal infection. She was subjected to ANC at the outpatient clinic every 2 weeks, where vaginal culture, complete blood count, prothrombin time, and C-reactive protein levels and serial ultrasonography were checked consistently. The fetus showed adequate growth. After 136 days, she delivered by elective cesarean section a male baby weighing 2850 g at 37 weeks of gestation with good recovery. In certain situations, delayed delivery of the second twin of diamniotic dichorionic twin pregnancy may be a safe, simple with less interventions, and effective option to improve pregnancy outcome.

Use of Machine Learning to Estimate the Per-Protocol Effect of Low-Dose Aspirin on Pregnancy Outcomes

In randomized clinical trials (RCTs), per-protocol effects may be of interest in the presence of nonadherence with the randomized treatment protocol. Using machine learning in per-protocol effect estimation can help avoid model misspecification owing to strong parametric assumptions, as is common with standard methods (eg, logistic regression). To demonstrate the use of ensemble machine learning with augmented inverse probability weighting (AIPW) for per-protocol effect estimation in RCTs and to evaluate the per-protocol effect size of aspirin on pregnancy. This secondary analysis used data from 1227 women in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a multicenter, block-randomized, double-blind, placebo-controlled clinical trial of the effect of daily low-dose aspirin on pregnancy outcomes in women at high risk of pregnancy loss. Participants were recruited at 4 university medical centers in the US from June 15, 2007, to July 15, 2012. Women were followed up for 6 menstrual cycles for attempted pregnancy and 36 weeks of gestation if pregnancy occurred. Follow-up was completed on August 17, 2012. Data analyses were performed on July 9, 2021. Daily low-dose (81 mg) aspirin taken at least 5 of 7 days per week for at least 80% of follow-up time relative to placebo. Pregnancy detected using human chorionic gonadotropin (hCG) levels. Among the 1227 women included in the analysis (mean SD age, 28.74 [4.80] years), 1161 (94.6%) were non-Hispanic White and 858 (69.9%) adhered to the protocol. Five machine learning models were combined into 1 meta-algorithm, which was used to construct an AIPW estimator for the per-protocol effect. Compared with adhering to placebo, adherence to the daily low-dose aspirin protocol for at least 5 of 7 days per week was associated with an increase in the probability of hCG-detected pregnancy of 8.0 (95% CI, 2.5-13.6) more hCG-detected pregnancies per 100 women in the sample, which is substantially larger than the estimated intention-to-treat estimate of 4.3 (95% CI, -1.1 to 9.6) more hCG-detected pregnancies per 100 women in the sample. These findings suggest that a low-dose aspirin protocol is associated with increased hCG-detected pregnancy in women who adhere to treatment for at least 5 days per week. With the presence of nonadherence, per-protocol treatment effect estimates differ from intention-to-treat estimates in the EAGeR trial. The results of this secondary analysis of clinical trial data suggest that machine learning could be used to estimate per-protocol effects by adjusting for confounders related to nonadherence in a more flexible way than traditional regressions. ClinicalTrials.gov Identifier: NCT00467363.

Effect of paternal health on pregnancy loss-A review of current evidence.

Pregnancy loss has multifactorial causes, and the maternal risk factors are the most investigated. Therefore, this review investigates the current literature regarding the effect of paternal health on pregnancy loss. This review is conducted according to the PRISMA guidelines. The electronic databases PubMed and Medline were the primary sources of information. The online tool covidence.org was used for the screening process. The Newcastle-Ottawa Scale was used for assessment of risk of bias across the non-RCT (Randomized Controlled Trials) included studies. Six cohort studies and one randomised clinical trial were included for assessment in this review. Especially three large retrospective studies reported that circulatory paternal health issue, increasing metabolic syndrome diagnoses and paternal age was significantly associated with a higher risk of pregnancy loss. Lower pregnancy loss was also found in couples with diabetes in the man compared to couples without diabetes. One study suggests a connection between varicocelectomy and improved sperm DNA fragmentation and lower abortion rate. This review confirms that paternal age, somatic health and particularly health regarding cardiovascular and metabolic disease are associated positively with risks of pregnancy loss. However, further research may lead to evidence, which are more conclusive.

Mathematical modeling of pregnancy loss with normal embryo karyotype in the first trimester

Introduction. The risk of pregnancy loss in the first trimester comprises 12.5-18.7 %. It is timely and relevant to develop methods for predicting miscarriage.Aim: to develop a predictive model for assessing a risk of miscarriage in case of normal embryo karyotype.Materials and Methods. The single-center cohort retrospective comparative study included 52 women with miscarriage at 6-12 weeks of gestation with normal embryo karyotype (main group) and 126 women with physiologically proceeding pregnancies and favorable perinatal outcomes (control group). All patients underwent general clinical and laboratory examination, analysis of genetic polymorphisms (FGBG -455A, F2 G20210A, F5 G1691A, F7 G10976A, F13 G103A, PAI-1 -675 5G/4G, ITGA2 C708T, ITGB3 T176C, MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, NOS3 T-786C, NOS3 C894T), spouse examination.Results. The factors associated with the loss of pregnancy turned out to be presented by a history of infertility, patient adenomyosis, a higher platelet count, as well as abnormal partner spermogram. Significant differences were obtained between the studied groups in the frequency of concurrent polymorphisms PAI-1 -675 5G/4G, MTHFR C677T, MTRR A66G, NOS3 G894T. Based on the identified patterns, a mathematical model has been developed allowing to determine the high risk of pregnancy loss in the first trimester (86.0 % efficiency).Conclusion. A comprehensive assessment of clinical and anamnestic indicators, molecular genetic parameters, spouse-related health indicators, it is possible to determine risk groups of pregnancy loss in case a normal embryo karyotype. Timely prediction provides the basis for optimizing preconception care and conducting timely prevention of miscarriage.

Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis

Background Spontaneous abortions are the most severe complication of early pregnancy and are a major reproductive health problem. Although this could be caused due to various cytogenetic, immunological, or endocrinological reasons, role of environmental toxicants cannot be ruled out. In order to explore the role of cadmium and lead in causing spontaneous abortions, current systematic review and meta-analysis had been carried out. Methodology Literature search was performed using appropriate keywords in PubMed, Science Direct, Cochrane Library, and Google Scholar databases up to December 25 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Metananalysis was carried out with the help of RevMan software (version 5.3). Results Meta-analysis of nine studies on cadmium concentrations in blood of women with at least one spontaneous abortions and controls revealed standardized mean difference (SMD)=3.39, 95% CI (2.17, 4.61), with p < .05. Similarly, meta-analysis of eight studies on lead concentrations revealed standardized mean difference (SMD)=6.24, 95% CI (4.34, 8.14), with p < .05. Conclusion Populations exposed to heavy metals such as cadmium and lead are at higher risk of pregnancy loss. Therefore, couples experiencing repeated pregnancy losses may be screened for heavy metal load.

Early embryo losses, progesterone and pregnancy associated glycoproteins levels during summer heat stress in dairy cows.

Objectives of this study were to characterize the effects of heat stress on pregnancy associated glycoproteins (PAG) and progesterone and its involvement in embryo survival. In trial 1, blood samples collected from days 29 to 36 post insemination were examined for the comparison of PAG concentrations between winter (n = 3721) and summer (n = 2388). In trial 2, embryo losses were assessed in winter (n = 144) and in summer (n = 133), in days 31 or 32 of pregnancy. Pregnancy diagnosis was carried out by ultrasonography on days 24 or 25, and it was repeated a week later; in the second occasion PAG concentration was also determined. In trial 3 the PAG and progesterone concentrations were assessed in days 33 to 36 in winter and summer. In trial 1 PAG levels did not differ between winter and summer, the conception rate and the proportion of uncertain pregnancies were higher in winter than summer. The likelihood of pregnancy was 10 to 15% higher in winter. In trial 2, the embryo death rate was higher in summer, but the PAG levels of cows that had embryo loss in summer were higher than those in winter. In both seasons, lower PAG levels were associated with higher risk of pregnancy loss, while embryo death was five times more likely to occur in summer than in winter and lower PAG concentrations were positively associated with higher risk of embryo loss. In trial 3, mean PAG levels were higher and of progesterone were lower during the summer than during the winter. We infer that despite the devastating effects of heat stress on cows' fertility, those early embryos that survive under continuous heat stress can form a well-functioning placenta; hence, the high embryo mortality rate observed during the summer months could be mainly attributed to luteal insufficiency.

Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data.

Is preconception paternal health associated with pregnancy loss? Poor preconception paternal health is associated with a higher risk of pregnancy loss as confirmed in sensitivity analyses accounting for maternal age and health. Preconception paternal health can negatively impact perinatal outcomes. Retrospective cohort study of US insurance claims database from 2009 to 2016 covering 958804 pregnancies. US insurance claims database including women, men and pregnancies within the USA between 2007 and 2016. Paternal preconception health status (e.g. metabolic syndrome diagnoses (MetS), Charlson comorbidity index (CCI) and individual chronic disease diagnoses) was examined in relation to pregnancy loss (e.g. ectopic pregnancy, miscarriage and stillbirth). In all, 958804 pregnancies were analyzed. The average paternal age was 35.3 years (SD 5.3) and maternal age was 33.1 years (SD 4.4). Twenty-two percent of all pregnancies ended in a loss. After adjusting for maternal factors, the risk of pregnancy loss increased with increasing paternal comorbidity. For example, compared to men with no components of MetS, the risk of pregnancy loss increased for men with one (relative risk (RR) 1.10, 95% CI 1.09-1.12), two (RR 1.15, 95% CI 1.13-1.17) or three or more (RR 1.19, 95% CI 1.14-1.24) components. Specifically, less healthy men had a higher risk of siring a pregnancy ending in spontaneous abortion, stillbirth and ectopic pregnancies. Similar patterns remained with other measures of paternal health (e.g. CCI, chronic diseases, etc.). When stratifying by maternal age as well as maternal health, a similar pattern of increasing pregnancy loss risk for men with 1, 2 or 3+ MetS was observed. A statistically significant but weak association between timing of pregnancy loss and paternal health was found. Retrospective study design covering only employer insured individuals may limit generalizability. Optimization of a father's health may improve pregnancy outcomes. National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085). M.L.E. is an advisor for Sandstone Diagnostics, Dadi, Hannah and Underdog. No other competing interests were declared. N/A.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Plague During Pregnancy: A Systematic Review.

Yersinia pestis continues to cause sporadic cases and outbreaks of plague worldwide and is considered a tier 1 bioterrorism select agent due to its potential for intentional use. Knowledge about the clinical manifestations of plague during pregnancy, specifically the maternal, fetal, and neonatal risks, is very limited. We searched 12 literature databases, performed hand searches, and consulted plague experts to identify publications on plague during pregnancy. Articles were included if they reported a case of plague during pregnancy and at least 1 maternal or fetal outcome. Our search identified 6425 articles, of which 59 were eligible for inclusion and described 160 cases of plague among pregnant women. Most published cases occurred during the preantibiotic era. Among those treated with antimicrobials, the most commonly used were sulfonamides (75%) and streptomycin (54%). Among cases treated with antimicrobials, maternal mortality and fetal fatality were 29% and 62%, respectively; for untreated cases, maternal mortality and fetal fatality were 67% and 74%, respectively. Five cases demonstrated evidence of Y. pestis in fetal or neonatal tissues. Untreated Y. pestis infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss. Appropriate antimicrobial treatment can improve maternal survival, although even with antimicrobial treatment, there remains a high risk of pregnancy loss. Limited evidence suggests that maternal-fetal transmission of Y. pestis is possible, particularly in the absence of antimicrobial treatment. These results emphasize the need to treat or prophylax pregnant women with suspected plague with highly effective antimicrobials as quickly as possible.

Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate

Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18–40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy.

Analysis of risk factors and predictors of pregnancy loss and strategies for the management of cervical insufficiency in pregnant women at a high risk of preterm birth

Aim To identify risk factors and predictors of pregnancy loss and to compare the efficacy of Arabin’s pessary with cervical cerclage in women at a high risk of pregnancy loss. Materials and methods This was a two-center retrospective case-control study that included 240 women at a high risk of preterm delivery. Group I (n = 161) included women who underwent insertion of the Arabin’s pessary between 14 and 24 weeks of pregnancy. Group II (n = 79) included women who had undergone circular cervical cerclage during the current pregnancy. All women included in the study received micronized vaginal progesterone at the dose of 200 mg/day until and including 34 weeks of gestation. Results Threatened pregnancy loss defined as spotting or vaginal bleeding in the first trimester was diagnosed in 29.8% (48/161) of patients in Group I versus 37.9% in Group II (p = .448). Postpartum bleeding occurred in 8.1% (13/161) in women in Group I versus 22.8% in Group II (χ 2 = 6.500; p = .011). Our study showed that cervical cerclage was most suitable for patients with history of obstetric complications, cervical length <15 mm, and large isthmic uterine fibroids. The use of the Arabin’s pessary reduced the rate of preterm births by 1.7-fold. A cluster analysis demonstrated that predictors of preterm birth in women with a high risk of pregnancy loss included: threatened pregnancy loss associated with chorionic/placental abruption, cervical incompetence, uterine fibroid growth to a large size, history of multiple spontaneous pregnancy losses, cervical tears during past labor, and gestational diabetes diagnosed for the first time during the current pregnancy. Conclusions Women with a high risk of pregnancy loss treated with Arabin’s pessary or cerclage plus vaginal progesterone had a term delivery rate of 70.4% (169/240). The combined strategy of pregnancy management allowed to markedly reduce the number of preterm births.

PREGNANCY LOSS IN WOMEN WITH HIV IS NOT ASSOCIATED WITH HIV MARKERS: DATA FROM A NATIONAL STUDY IN ITALY, 2001-2018

BackgroundThere is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease.MethodsMulticenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses.ResultsAmong 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046–1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407–4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178–2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage.ConclusionsOlder women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.

Coagulation Biomarkers in Women with Recurrent Miscarriage and Polycystic Ovarian Syndrome: Systematic Review and Meta-Analysis

Introduction Pregnant women with polycystic ovarian syndrome (PCOS) have high risk of pregnancy loss. Pathophysiological mechanisms appear to be associated with obesity, hormonal factors, or blood clotting disorders. Our aim is to perform a systematic review and meta-analysis on the relationship between coagulation disorders and risk of recurrent miscarriage (RM) in patients with PCOS and to identify coagulation biomarkers for this condition. Material and Methods PubMed and MEDLINE databases were searched for publications in English language. The search terms used included “RM”, “polycystic ovary syndrome”, “coagulation disorders”, and “thrombophilia”. Odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage in different RM groups (with and without PCOS). Results A total of 575 publications including the search terms were identified. Six studies were included for qualitative analysis, and five were included for quantitative analysis (meta-analysis). We found no association between RM and inherited thrombophilias in patients with PCOS: (1) Factor V Leiden (OR, 0.74; 95% CI, 0.38 – 1.45; p = 0.38); (2) C677T methylenetetrahydrofolate reductase polymorphism (MTHFR) (OR, 1.01; 95% CI, 0.64 – 1.59; p = 0.97); and (3) A1297C MTHFR polymorphism (OR, 1.08; 95% CI, 0.62 – 1.89; p = 0.77). Other potential biomarkers were identified, with emphasis on plasminogen activator inhibitor type 1. Conclusion Data available in the current literature revealed that there was no association between RM and inherited thrombophilias in patients with PCOS. RM patients with PCOS have a high risk of thromboembolic events.