RESUMEN
BACKGROUND: One in four pregnancies end in a pregnancy loss. Although the effect on couples is well documented, evidence-based treatments and prediction models are absent. Fetal aneuploidy is associated with a higher chance of a next successful pregnancy compared with euploid pregnancy loss in which underlying maternal conditions might be causal. Ploidy diagnostics are therefore advantageous but challenging as they require collection of the pregnancy tissue. Cell-free fetal DNA (cffDNA) from maternal blood has the potential for evaluation of fetal ploidy status, but no large-scale validation of the method has been done. METHODS: In this prospective cohort study, women with a pregnancy loss were recruited as a part of the Copenhagen Pregnancy Loss (COPL) study from three gynaecological clinics at public hospitals in Denmark. Women were eligible for inclusion if older than 18 years with a pregnancy loss before gestational age 22 weeks (ie, 154 days) and with an intrauterine pregnancy confirmed by ultrasound (including anembryonic sac), and women with pregnancies of unknown location or molar pregnancies were excluded. Maternal blood was collected while pregnancy tissue was still in situ or within 24 h after pregnancy tissue had passed and was analysed by genome-wide sequencing of cffDNA. Direct sequencing of the pregnancy tissue was done as reference. FINDINGS: We included 1000 consecutive women, at the time of a pregnancy loss diagnosis, between Nov 12, 2020, and May 1, 2022. Results from the first 333 women with a pregnancy loss (recruited between Nov 12, 2020, and Aug 14, 2021) were used to evaluate the validity of cffDNA-based testing. Results from the other 667 women were included to evaluate cffDNA performance and result distribution in a larger cohort of 1000 women in total. Gestational age of fetus ranged from 35-149 days (mean of 70·5 days [SD 16·5], or 10 weeks plus 1 day). The cffDNA-based test had a sensitivity for aneuploidy detection of 85% (95% CI 79-90) and a specificity of 93% (95% CI 88-96) compared with direct sequencing of the pregnancy tissue. Among 1000 cffDNA-based test results, 446 (45%) were euploid, 405 (41%) aneuploid, 37 (4%) had multiple aneuploidies, and 112 (11%) were inconclusive. 105 (32%) of 333 women either did not manage to collect the pregnancy tissue or collected a sample classified as unknown tissue giving a high risk of being maternal. INTERPRETATION: This validation of cffDNA-based testing in pregnancy loss shows the potential and feasibility of the method to distinguish euploid and aneuploid pregnancy loss for improved clinical management and benefit of future reproductive medicine and women's health research. FUNDING: Ole Kirks Foundation, BioInnovation Institute Foundation, and the Novo Nordisk Foundation.
Asunto(s)
Aborto Espontáneo , Ácidos Nucleicos Libres de Células , Embarazo , Humanos , Femenino , Lactante , Recién Nacido , Estudios Prospectivos , Feto , Aneuploidia , ADN , Diagnóstico Prenatal/métodosRESUMEN
Research has focused on optimizing luteal phase support and endometrial receptivity in ovarian stimulation cycles. In this study, serial endocrine measurements were taken in 600 patients after a gonadotrophin-releasing hormone antagonist stimulation protocol. On the day of blastocyst transfer, serum progesterone and oestradiol were similar irrespective of a subsequent positive or negative pregnancy test (median 99 ng/ml versus 103 ng/ml for progesterone, respectively) or a subsequent live birth or pregnancy loss. Serum progesterone was significantly correlated to each ovarian response parameter (total number of follicles, number of oocytes retrieved and oestradiol concentration; r = 0.45, 0.57 and 0.54 respectively, all P < 0.0001). These correlations were consistent irrespective of clinical outcome. On the day of the pregnancy test, these correlations had vanished except in the live birth subgroup showing a weaker correlation (r = 0.22, 0.27 and 0.32 respectively, all P < 0.005). The lowest HCG and progesterone levels associated with live birth were 59.3 IU/l and 12.3 ng/ml, respectively. Fourteen out of 92 patients (15.2%) with pregnancy loss had normal HCG but low progesterone levels (above and below their respective 5th percentile), and miscarried before the end of the 7th week, when the luteal-placental shift occurs.
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Transferencia de Embrión , Estradiol/sangre , Fase Luteínica/sangre , Inducción de la Ovulación , Progesterona/sangre , Adulto , Femenino , Fertilización In Vitro/métodos , Humanos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Pronóstico , Resultado del TratamientoRESUMEN
This study aimed to develop a dynamic model for predicting outcome during the first trimester of pregnancy using baseline demographic data and serially collected blood samples and transvaginal sonographies. A prospective cohort of 203 unselected women with an assumed healthy pregnancy of < 8 weeks' gestation was followed fortnightly from 4-14 weeks' gestation until either miscarriage or confirmed first trimester viability. The main outcome was development of a model to predict outcome from gestational age-dependent hazard ratios using both baseline and updated serial data from each visit. Secondary outcomes were descriptions of risk factors for miscarriage. The results showed that 18% of the women experienced miscarriages. A fetal heart rate detected before 8 weeks' gestation indicated a 90% (95% CI 85-95%) chance of subsequent delivery. Maternal age (≥ 35 years), insufficient crown-rump-length (CRL) and mean gestational sac diameter (MSD) development, and presence of bleeding increased the risk of miscarriage. Serum biomarkers, including hCG, progesterone, and estradiol, were found to impact the risk of miscarriage with estradiol as the most important. The best model to predict miscarriage was a combination of maternal age, vaginal bleeding, CRL, and hCG. The second-best model was the sonography-absent model of maternal age, bleeding, hCG, and estradiol. This study suggests that combining maternal age, and evolving data from hCG, estradiol, CRL, and bleeding could be used to predict fetal outcome during the first trimester of pregnancy.Trial registration ClinicalTrials.gov identifier: NCT02761772.
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Aborto Espontáneo , Resultado del Embarazo , Embarazo , Humanos , Femenino , Adulto , Aborto Espontáneo/etiología , Estudios Prospectivos , Ultrasonografía Prenatal/métodos , Primer Trimestre del Embarazo , Biomarcadores , EstradiolRESUMEN
The concept of sensory delivery rooms was introduced in 2013. These rooms offer programmable calming lights, restful blurred pictures displayed on a wall-sized big screen, and sound effects. The primary aim of this observational study was to analyse the risk of obstetrical interventions among women giving birth for the first-time in a sensory delivery room vs. a standard delivery room. We included nulliparous, term pregnant women having a single baby with a cephalic presentation who were in spontaneous labour and gave birth between March 1st 2014 and July 1st 2015 in North Zealand Hospital, Hillerød. A total of 789 women were included in the study, 313 gave birth in a sensory room and 476 in a standard delivery room. The risk of a caesarean delivery was significantly decreased when giving birth in a sensory room compared with a standard delivery room (OR, multiple adjusted: 0.44; 95% CI 0.22-0.87); furthermore, the use of oxytocin infusion was also reduced (OR, multiple adjusted: 0.71; 95% CI 0.50-1.03). This observational cohort study suggests that giving birth in a sensory delivery room could lower the risk of caesarean delivery, potentially reducing the number of such deliveries by one for every 23 patients.
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Salas de Parto/normas , Parto Obstétrico , Estética , Adulto , Cesárea , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Oxitocina/uso terapéutico , Embarazo , Estudios RetrospectivosRESUMEN
We describe a rare case of bilateral tubal pregnancy following natural conception in a woman with no other known risk factor than two former caesarean sections. Intraabdominal adhesions following the caesarean sections complicated the salpingectomy thus diminishing certainty of a healthy contralateral tube. The woman was readmitted three weeks later and had an additional salpingectomy on behalf of an unrecognized tubal pregnancy. Considering the rising caesarean section rates clinicians need to be certain of no additional ectopic pregnancy while performing the primary operation.
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Embarazo Tubario , Adulto , Cesárea Repetida/efectos adversos , Femenino , Humanos , Embarazo , Embarazo Tubario/diagnóstico por imagen , Embarazo Tubario/etiología , Embarazo Tubario/cirugía , Factores de Riesgo , Salpingectomía , UltrasonografíaRESUMEN
INTRODUCTION: Off-label use of the prostaglandin-E1 analogue misoprostol has become standard practice when inducing labour. In Denmark, a low-dosage misoprostol regimen is common. The regimen consists of one 25 µg application on the first day of induction. The registered prostaglandin-E2 analogue dinoprostone is used in 3 and 6 mg doses. This study compared induction procedures with dinoprostone and misoprostol in terms of induction time, foetal outcome and maternal outcome. MATERIAL AND METHODS: This retrospective study included 1,645 induced deliveries from two periods: 2003-2005, when dinoprostone was standard treatment (n = 635), and 2008-2010, when misoprostol was standard treatment (n = 633). We evaluated the induction method, outcomes and confounders using Kaplan-Meier, Cox and logistic regression analyses. RESULTS: In the first 24 h, 38% and 59% of women delivered in the misoprostol and dinoprostone groups, respectively. Compared with dinoprostone, misoprostol was associated with a longer induction time (hazard ratio = 0.79, 95% confidence interval (CI): 0.69-0.90). Both regimens showed similar risks of caesarean section (odds ratio (OR) = 0.88, 95% CI: 0.64-1.12), rates of meconium-stained amniotic fluid (OR = 0.85, 95% CI: 0.63-1.15), 5-min Apgar scores < 7 (OR = 1.73, 95% CI: 0.34-8.75), and transfers to neonatal intensive care units (OR = 0.64, 95% CI: 0.38-1.08). CONCLUSION: Low-dosage misoprostol required more time than dinoprostone to induce labour, but the two drugs were equally safe in terms of the risk of caesarean section and foetal outcomes. FUNDING: The Danish Ministry of Research and Innovation (#10-093833). TRIAL REGISTRATION: The Danish Data Protection Agency (#2011-41-5794).