Higher Risk Of Miscarriage Research Articles

Risk of adverse fetal outcomes following nonobstetric surgery during gestation: a nationwide population-based analysis

BackgroundLiterature suggests that nonobstetric surgery during gestation is associated with a higher risk of spontaneous abortion, prematurity, and a higher cesarean section rate, but the direct impact on fetal outcomes is still unclear. In this study, we aimed to investigate whether nonobstetric surgery during pregnancy is associated with negative fetal outcomes by analysing a nation-wide database in Taiwan.MethodsThis population-based retrospective observational case–control study was based on the linkage of Taiwan’s National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database between 2004 and 2014. For every pregnancy with nonobstetric surgery during gestation, four controls were randomly matched according to maternal age and delivery year. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) of adverse fetal outcomes with the non-surgery group as the reference. The primary outcomes involved stillbirth, prematurity, low birth weight, low Apgar scores, and neonatal and infant death.ResultsAmong 23,721 identified pregnancies, 4,747 underwent nonobstetric surgery. Pregnancies with nonobstetric surgery had significantly higher risks of prematurity (aOR: 1.46; 95% CI: 1.31–1.62), lower birth weight (aOR: 1.49; 95% CI: 1.33–1.67), Apgar scores < 7 (1 min, aOR: 1.58; 95% CI: 1.33–1.86; 5 min, aOR: 1.34; 95% CI: 1.03–1.74), neonatal death (aOR: 2.01; 95% CI: 1.18–3.42), and infant death (aOR: 1.69; 95% CI: 1.12–2.54) than those without nonobstetric surgery after adjustment for socioeconomic deprivation, hospital level, and other comorbidities. Surgery performed in the third trimester was associated with a significantly increased rate of prematurity (aOR: 1.38; 95% CI: 1.03–1.85), but lower rates of stillbirth (aOR: 0.1; 95% CI: 0.01–0.75) and Apgar score < 7 at the 5th minute (aOR: 0.2; 95% CI: 0.05–0.82), than surgery performed in the first trimester.ConclusionsPregnancies with nonobstetric surgery during gestation were associated with increased risks of prematurity, low birth weight, low Apgar scores, neonatal and infant death, longer admission, and higher medical expenses than those without surgery. Furthermore, surgery in the third trimester was associated with a higher rate of prematurity than surgery performed in the first trimester.Trial registrationNot applicable.

Is the lack of prior exposure to sperm antigens associated with worse neonatal and maternal outcomes? A 10-year single-center experience comparing ICSI-TESE pregnancies to ICSI pregnancies.

Nowadays, pathogenesis of preeclampsia (PE) is still unknown. Among the different etiological hypotheses, some authors proposed that it might be because of an abnormal immunologic response to a foreign fetal antigen derived from the father's spermatozoa. Indeed, the fetus is considered a semi-allograft, being one half paternally derived in its antigenicity, and the first pathogenic insult of PE may be an abnormal maternal immune response toward this semi-allogenic implant. In the context of artificial reproductive techniques, it has been shown that the use of donor and surgically retrieved spermatozoa (e.g., testicular sperm extraction [TESE]) increases the risk of PE, confirming the protective effect of sperm exposure on maternal complications. Determining whether the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained through intracytoplasmic sperm injection after TESE (ICSI-TESE) for obstructive azoospermia (OA). This is a single-center case-control retrospective study, focusing on all first pregnancies obtained through ICSI-TESE for OA at Humanitas Fertility Center between January 1, 2010 and December 31, 2019. Controls included patients that achieved their first pregnancy with ICSI and ejaculated spermatozoa, for a diagnosis other than azoospermia, in the same time period. Cases were matched with controls in a 1:2 ratio, considering female age, female BMI, and year of controlled ovarian stimulation. The primary outcome measure was the delivery rate, defined as the number of deliveries divided by the total number of clinical pregnancies. Secondary outcome measures focused on maternal and neonatal complications, such as miscarriage rate, rate of main obstetric complications, prematurity rate, and rate of congenital malformations. By analyzing overall 113 pregnancies among cases and 214 pregnancies among controls, this study showed that the delivery rate was higher in controls with respect to cases (92.06% vs. 84.07%, p=0.026); among deliveries, live births were 98.95% and 100%, respectively, whereas only one stillbirth occurred in cases. The first trimester miscarriage rate was higher in the cases than controls (13.27% vs. 6.07%, p=0.027), whereas no difference was found among the rate of second trimester miscarriages, therapeutic abortions, and ectopic pregnancies. There was no difference regarding the rate of maternal complications, including gestational hypertension, PE, HELLP syndrome, gestational diabetes, placenta previa, placental abruption, and premature rupture of the membranes. Considering neonatal complications, it was shown that twins belonging to controls had a higher prematurity rate with respect to cases (65.79% vs. 50.00%) but without a statistical relevance. Lastly, the rate of congenital malformations did not differ among the two groups. This study showed that, once couples diagnosed with OA achieve a pregnancy, they have a much higher risk of miscarriage in the first trimester in respect to non-azoospermic patients. Moreover, controls had a higher delivery rate in respect to cases; however, when the fetal status at birth was compared, no difference was found between live births and stillbirths. Differently from the findings in the literature, no association with PE was found. This might be related to a collider bias/left truncation bias: As azoospermic patients are at higher risk of early termination of pregnancy, it results that they do not have the possibility to develop PE and other adverse outcomes.

COVID-19 vaccines in pregnancy.

COVID-19 caused by SARS-CoV-2 coronavirus has been associated with severe illness in pregnant women. Furthermore, COVID-19 during pregnancy is associated with adverse fetal outcomes including preterm labor. Pregnant women were largely excluded from initial clinical trials investigating the safety and efficacy of COVID-19 vaccines; however, they have since been included as part of the routine roll-out of these vaccines. This narrative review synthesizes the evidence on the safety, immunogenicity, and effectiveness predominantly of the mRNA COVID-19 vaccines which have been most widely used in pregnant women.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. PROSPERO, CRD42018090866.

Comparison of two endometrial preparation methods for frozen-thawed embryo transfer in anovulatory PCOS patients: Impact on miscarriage rate

ObjectiveSome studies have suggested that patients with polycystic ovary syndrome (PCOS) are at high risk of miscarriage. However, this still remains controversial. Several potential factors might explain this association: obesity, hyperinsulinemia and hyperandrogenism. Artificial and stimulated cycles appear to be comparable for endometrial preparation in frozen-thawed embryo transfer (FET) in PCOS patients. Only a few studies have assessed miscarriage rates specifically in PCOS. We have evaluated the impact of endometrial preparation on FET outcomes in anovulatory PCOS patients. MethodsA retrospective cohort study was conducted at the Lille University Hospital, including 255 FET cycles in 134 PCOS patients between January 2011 and December 2017. PCOS was defined by the presence of at least two of the three Rotterdam's criteria. Patients were under 35 years old. Two endometrial preparation protocol were studied: stimulated cycle (gonadotropins on the second day of the cycle and luteal phase support including natural progesterone 600 mg/day) and artificial cycle (6 mg oral estradiol valerate and 800 mg micronized vaginal progesterone daily). Results137 FET were performed under stimulated cycle and 118 FET under artificial cycle. Early pregnancy rates (30% versus 37.3%, p = NS), miscarriage rates (22% versus 25%, p = NS) and live birth rates (23.4% versus 26.3%, p = NS) were similar. ConclusionsIn anovulatory PCOS women, the type of endometrial preparation does not influence FET outcomes, specifically regarding the miscarriage rate.

Menstrual cycle characteristics as an indicator of fertility outcomes: evidence from prospective birth cohort study in China.

To evidently assess the applicability of regulate menstrual cycle (MC) characteristics in Traditional Chinese Medicine (TCM) as an indicator for fertility. A community-based prospective cohort study was conducted in China. Between January 2010 and December 2012, women who were willing to conceive within 2 years were enrolled in the study. Other than the MC length pattern, a well-adopted MC characteristic, menstrual blood color and clots were specifically concerned for women enrolled. All participants were followed up in 2 years by trained nurses. Pregnancy rate, fecundability odds ratio () and risk of miscarriage were assessed as fertility outcomes. A total of 2109 women were effectively included in this cohort for analysis. Results show that women with irregular MC length were less likely to achieve conception (= 0.59; 95% = 0.45-0.77, < 0.001). Menstrual blood in bright red color was also associated with decline in likelihood of conception ( = 0.79; 95% = 0.63-0.98, = 0.04). Women with menstrual blood in light red were at higher risk of miscarriage ( = 2.39; 95% = 0.91-6.28, = 0.08). No significant impact was found between menstrual blood clots and fertility outcomes ( = 1.02, 95% = 0.83-1.25, = 0.88; = 1.26 95% = 0.77-2.07, = 0.35). MC characteristics can be an effective and simple indicator for women's fertility. Increasing the knowledge of MC characteristics for women in reproductive ages would bring great benefits to their preconception health conditions.

Protein-rich food intake and risk of spontaneous abortion: a prospective cohort study

Diet quality is increasingly recognized as important for human reproductive capacity. We studied the association between intake of protein-rich foods and risk of spontaneous abortion (SAB). During 2013-2020, we recruited pregnancy planners from the United States and Canada (Pregnancy Study Online; PRESTO) and Denmark (SnartForaeldre.dk; SF). Participants completed a baseline questionnaire and a validated cohort-specific food frequency questionnaire. We estimated preconception intake of red meat, poultry, processed meat, seafood, eggs, plant-based proteins, and dairy from individual foods and mixed recipes. We included 4,246 PRESTO and 2,953 SF participants who reported a pregnancy during the study. Data on SAB were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI), representing the effect of substituting one type of protein-rich food for another. SAB risk was 23% in PRESTO and 16% in SF. In PRESTO, substitution of seafood with other protein-rich foods was associated with higher SAB risk [for example, the HR for replacing 100g of seafood/week with 100g of red meat was 1.10 (95% CI 1.00, 1.20)]. In contrast, in SF, substituting seafood with other protein-rich foods was associated with lower SAB risk [HR for replacing 100g of seafood/week with 100g of red meat was 0.89 (95% CI 0.82, 0.98)]. Other protein-rich food substitutions were not meaningfully associated with SAB risk. Preconception intake of protein-rich foods was largely unrelated to SAB risk, with the exception of seafood, which was associated with higher risk of SAB in Denmark, but a lower risk in North America.

Predictors of adverse pregnancy outcomes among Kenyan women with HIV on antiretroviral treatment in pregnancy.

The aim of this study was to understand predictors of adverse pregnancy outcomes (APOs) among women on antiretroviral treatment (ART). A longitudinal cohort. Participants from the Mobile WAChX trial were evaluated for APOs, including stillbirth (fetal death at ≥20 weeks' gestation), preterm birth (PTB, livebirth at <37 weeks' gestation,) and neonatal death (NND, ≤28 days after live birth). Predictors were determined by univariable and multivariable Cox proportional hazards and log-binomial models. Among 774 women included, median age was 27 years and 29.0% had unsuppressed HIV viral load (>1000 copies/ml) at enrollment. Half (55.1%) started ART prepregnancy, 89.1% on tenofovir-based regimens. Women with depression had a higher risk of stillbirth (adjusted hazard ratio [aHR] 2.93, 95% confidence interval (95% CI) 1.04-8.23), and women with lower social support score had higher risk of late stillbirth (aHR 11.74, 2.47-55.86). Among 740 livebirths, 201 (27.2%) were preterm and 22 (3.0%) experienced NND. PTB was associated with unsuppressed maternal viral load (adjusted prevalence ratio [aPR] 1.28, 95% CI 1.02-1.61), intimate partner violence (IPV) in pregnancy (aPR 1.94, 95% CI 1.28-2.94), and history of any sexually transmitted infection (STI) (aPR 1.63, 95% CI 1.06-2.51). NND was associated with PTB (aPR 2.53, 95% CI 1.10-5.78) and STI history (aPR 4.25, 95% CI 1.39-13.06). Most associations retained significance in the subgroup of women with viral suppression. Maternal viremia during pregnancy predicted PTB as did IPV, lower education, and STI history, while psychosocial stressors predicted stillbirth. Implementing mental health services, ART adherence, partner support, and routine STI screening and treatment could reduce APOs among women with HIV in sub-Saharan Africa settings.

CURRENT APPROACH TO PREGNANT WOMEN WITH THYROID ABNORMALITIES

The course of pregnancy, thyroid status, and hormonal background were studied in 96 women with autoimmune thyroiditis (AIT). It was established that pregnant women have a number of maternal and fetal complications (54.8%); AIT has an adverse effect on the course of pregnancy; a high risk of miscarriage and termination of pregnancy is observed; and the thyroid hormone level is reduced and the TSH level is increased in comparison with that in healthy pregnant women. To prevent gestational complications and prematurity in women with AIT, routine blood TSH testing from early gestation is recommended.

Effect of Grand Multiparity on the Adverse Birth Outcome: A Hospital-Based Prospective Cohort Study in Sidama Region, Ethiopia.

BackgroundAdverse birth outcome is associated with grand multiparity and is still a major public health problem in developing countries. There is limited information that investigates the effect of grand multiparity on perinatal outcomes in a prospective follow-up design in Ethiopia. Therefore, this study was aimed to investigate the effect of grand multiparity on the occurrence of adverse perinatal outcomes in the Sidama Region of Ethiopia.MethodsWe conducted a prospective follow-up study among 837 women who gave birth in selected public hospitals of the Sidama Region from January 1 to August 31, 2021. Data were collected using a structured questionnaire and medical record review. A modified Poisson regression model with robust standard errors was applied to estimate the adjusted risk ratio and its 95% CI of the risk factors for adverse perinatal outcomes to examine the association of the multi-parities with the adverse birth outcome. STATA Version 14 was used for analysis.ResultsThe overall cumulative incidence of adverse perinatal outcomes was 33% (95% CI: 29.9%, 36.4%). After adjusted for confounders, women with grand multiparity gave birth to babies with a higher risk of stillbirth (ARR = 1.6; 95% CI: 1.01–2.51), macrosomia (ARR = 1.6; 95% CI: 1.23–2.07), and preterm birth (ARR = 1.3; 95% CI: 1.1–1.66) compared to their counterparts.ConclusionHigh incidences of adverse perinatal outcomes occurred among women with grand multiparity. We recommend that the region and districts health bureau should give close monitoring for pregnant women with high parity throughout their prenatal, intrapartum, and postpartum periods.

MANAGEMENT OF PREGNANT WOMEN WITH THYROID DISEASE

The course of pregnancy, thyroid status, hormonal levels were studied in 96 women with autoimmune thyroiditis (AIT). It was found that pregnant women have a number of complications (54.8%) from the mother and the fetus, AIT has an unfavorable effect on the course of pregnancy, there is a high risk of miscarriage and termination of pregnancy, there is a decrease in the level of thyroid hormones and an increase in the level of TSH in comparison with similar indicators of healthy pregnant women. For the prevention of complications of gestation and prematurity of pregnancy in women with AIT, a planned determination of TSH blood from early gestation is recommended.

External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis.

Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal first trimester iron status and its association with obstetric and perinatal outcomes.

To assess the following in singleton pregnant women: (1) associations between first trimester iron deficiency and obstetric and perinatal outcomes, (2) overall first trimester iron status and (3) post-treatment iron status after intensified iron supplementation. A prospective cohort study was conducted with linkage of first trimester hemoglobin and plasma ferritin with obstetric and perinatal data from a hospital database. Blood sample data were obtained from a Danish University Hospital. The cohort was divided into groups according to ferritin and hemoglobin: (1) iron-deficient anemic (ferritin < 30ng/mL and Hb < 110g/L), (2) iron-deficient non-anemic (ferritin < 30ng/mL and Hb ≥ 110g/L), and (3) iron-replete non-anemic (ferritin 30-200ng/mL and Hb ≥ 110g/L). Obstetric and perinatal outcomes in each iron-deficient group were compared to the iron-replete non-anemic group using multivariable logistic regression. The effect of 4weeks intensified iron supplementation on hemoglobin and ferritin was assessed by groupwise comparisons. The cohort comprised 5763 singleton pregnant women, of which 14.2% had non-anemic iron deficiency, and 1.2% had iron-deficiency anemia. Compared to iron-replete non-anemic women, iron-deficient anemic women had a higher risk of gestational diabetes (aOR 3.8, 95% CI 1.4-9.0), and iron-deficient non-anemic women had a higher risk of stillbirth (aOR 4.0, 95% CI 1.0-14.3). In group 1 and 2, 81.5% and 67.7% remained iron-deficient after intensified iron supplementation. Iron-deficiency anemia was associated with gestational diabetes, and non-anemic iron deficiency with stillbirth, although risk estimates were imprecise due to few events. Iron deficiency was present in 15.4% and often persisted despite 4weeks intensified iron supplementation.

A Prospective Study of the Relationship Between Sleep Quality and Depression in Pregnancy

Objective Poor sleep and depression are common problems during pregnancy, but there has been little investigation into the association between them. This prospective study aims to examine the relationship between sleep quality and depression during pregnancy. Methods Pregnant women under 14 weeks’ gestation attending routine outpatient antenatal care in Singapore’s largest maternity hospital were recruited between 2012 and 2014. Women with multiple pregnancies and deemed at high risk of miscarriage were excluded. Six hundred and forty participants completed the Pittsburgh Sleep Quality Index (PSQI) and Edinburgh Postnatal Depression Scale (EPDS) at the three trimesters during pregnancy. Results Mean PSQI score was highest in the third visit, suggesting poorer quality sleep in the late third trimester compared to other trimesters. 15.6% of participants at each time point fulfilled the criteria for antenatal depression according to the EPDS cut-off score &gt; 14. PSQI scores were significantly correlated with EPDS scores, and also prospectively predicted EPDS scores in all three trimesters. Conclusion Sleep quality in Singaporean pregnant women was poorest in the third trimester, and was associated with the development of depressive symptoms. With more than 1 in 10 women having antenatal depression, interventions targeting sleep quality might be particularly beneficial.

ОСОБЛИВОСТІ ПЕРЕБІГУ ВАГІТНОСТІ ТА РОЗРОДЖЕННЯ ЖІНОК З ЕКСТРАКОРПОРАЛЬНИМ ЗАПЛІДНЕННЯМ З ГРУПИ ВИСОКОГО РИЗИКУ ПО ВИНИКНЕННЮ ПЕРЕДЧАСНИХ ПОЛОГІВ

The article is a part of the research project at the Department of Obstetrics and Gynecology No.2 of Higher Education Institution Poltava State Medical University "The role of chronic infection of the uterus and lower genital tract in the formation of obstetric and gynecological pathology" (state registration No. 0117U005276, implementation period 2017-2022). In modern reproductive medicine, infertility in marriage is considered a problem of particular importance. That is why modern assisted reproductive technologies are chosen as a method of treatment for many married couples, and their increased application necessitates intensive monitoring of the course of pregnancy and delivery. Pregnant women after in vitro fertilization programs are at high risk of miscarriage and preterm birth. The aim of the research was to study the features of pregnancy, childbirth and the condition of newborns in women after in vitro fertilization, which are classified as high risk for preterm birth. Women were included in the study at 18-20 weeks 6 days of pregnancy. We examined 85 women who became pregnant after in vitro fertilization (study group A: 37 pregnant women who refused preventive treatment and received medications in accordance with regulations; study group B: 48 pregnant women who have received the proposed treatment since their inclusion in the study. The control group included 20 apparently healthy pregnant women with its natural pregnancy onset. In pregnant women of study group A, pregnancies ended in premature birth by 1.7 times more often, and most of them occurred before 34 weeks; during pregnancy, there was a greater risk of preterm birth, which required enhanced correction in addition to conservative measures: suturing the cervix and the use of obstetric unloading pessary; the frequency of delivery by cesarean section prevailed by 1.3 times. Moreover, only in this group, pathological bleeding was observed, surgery was performed and perinatal mortality was recorded. Pregnant women who agreed to preventive treatment developed fewer preterm births after 34 weeks. Complications of pregnancy and childbirth were much less common in these women. Surgical intervention in childbirth and the frequency of delivery by cesarean section were also much less common.

Growth Disorders in Twins: An Individual Participant Data Meta-Analysis of Perinatal Mortality

In uncomplicated dichorionic (DC) and monochorionic (MC) twin pregnancies with normally grown fetuses, the optimal time of delivery is 37 and 36 weeks, respectively. The influence of growth discordance on the optimal time of birth, with or without small for gestational age (SGA, < 10th centile), is unknown. We aimed to determine the optimal timing of birth by evaluating the rates of stillbirth (SB) and neonatal death (NND) in women with DC and MC twins with different levels of growth discordance and in relation to SGA. We performed an Individual Participant Data Meta-Analysis of studies reporting rates of SB and NND in women with twin pregnancies from 34-41 weeks (PROSPERO ID: CRD42018090866). Monoamniotic twin pregnancies were excluded. The prospective risk of perinatal death was calculated as the difference between the prospective risk of SB and risk of NND per gestational week. Analyses were stratified by chorionicity, different intervals of growth discordance and presence of SGA in one or both twins. We did not analyse data about associated obstetric complications or abnormal ultrasound findings. We included 20 studies reporting on 7474 women with DC and 2281 women with MC twin pairs. For both DC and MC twins the absolute risks of SB and NND were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance or presence of SGA, women with DC and MC twins had higher risk of SB than NND from 37 weeks onwards (Fig. 1, Fig. 2). For MC twins, the nadir was between 36-37 weeks. The nadir for perinatal mortality risk for women with DC twins with growth discordance or SGA is around 37 weeks. For MC twins this is between 36-37 weeks, favouring delivery from 37 weeks onward. Growth discordance or SGA is associated with higher absolute SB and neonatal risks but does not largely influence the optimal timing of birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Obesity and oocyte quality: significant implications for ART and emerging mechanistic insights.

The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome, and other noncommunicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of assisted reproductive technology (ART), compared to women of normal body mass index, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development, or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

Paternal inflammatory arthritis is associated with a higher risk of miscarriage: results of a large multicentre study (iFAME-Fertility).

ObjectivesPaternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA.MethodsWe performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA.ResultsIn total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015].ConclusionsThis is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.

Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997\u20132017

BackgroundNitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth.MethodsWe conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L.ResultsDrinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)].ConclusionsThe association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

Contemporary Features Of Predicting The Development Of Luteal Insufficiency And Related Gestational Disorders

The goal of our study was a comprehensive assessment of obstetric, gynecological, somatic and genetic factors, contributing to high risk of insufficient luteal phase (ILP) and relating gestational disorders to the latter in relevant patients for further optimization of therapeutic and preventive measures. Material and Methods — A cohort study with a mixed cohort was carried out. The clinical material of the retrospective study was presented based on the results of analyzing 300 cases of patients with verified diagnoses of the threat of spontaneous abortion, miscarriage, and complete spontaneous abortion, who were hospitalized in the period of 2018-2020. As part of a prospective study, we analyzed 66 blood samples of women treated at the State Budgetary Healthcare Institution Simferopol Clinical Maternity Hospital No.2 in Crimea in 2020. The polymerase chain reaction method in real time mode, with the use of the developed kits, was used for CYP3A5 6986A&gt; G polymorphism. Results — A comprehensive assessment of obstetric, gynecological, somatic and genetic factors allowed identifying the most informative prognostic markers for the risk of developing luteal phase insufficiency and related gestational disorders, including irregular menstrual cycle, cases of drug-induced abortion, preceding specific infectious diseases (chlamydia, Ureaplasma urealyticum infection), gynecological pathology (polycystic ovary syndrome), surgical interventions performed for gynecological pathology (ovarian resection and ovariectomy), as well as single nucleotide polymorphism rs776746 in the CYP3A5 gene. Conclusion — The identified prognostic criteria make it possible to identify a group of patients with a high risk of miscarriage even before the conception; such patients need more careful and systematic medical monitoring for the timely diagnosis of possible pregnancy complications. Early diagnosing of potential issues would allow clinicians to take preventive measures, along with initiating timely treatment. As a result, the percentage of reproductive losses would go down.