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European Journal of Obstetrics,... Sep 2023A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous... (Review)
Review
A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous cesarean section. The continuous increase of Cesarean Deliveries is causing a parallel increase in CSP and its complications. Considering its high morbidity, the most usual recommendation has been termination of pregnancy in the first trimester; however, several cases progress to viable births. The aim of this systematic review is to evaluate the outcome of CSP managed expectantly and understand whether sonographic signs could correlate to the outcomes. An online-based search of PubMed and Cochrane Library Databases was used to gather studies including women diagnosed with a CSP who were managed expectantly. The description of all cases was analysed by the authors in order to obtain information for each outcome. 47 studies of different types were retrieved, and the gestational outcome was available in 194 patients. Out of these, 39 patients (20,1%) had a miscarriage and 16 (8,3%) suffered foetal death. 50 patients (25,8%) had a term delivery and 81 (41,8%) patients had a preterm birth, out of which 27 (13,9%) delivered before 34 weeks of gestation. In 102 (52,6%) patients, a hysterectomy was performed. Placenta Accreta Spectrum (PAS) was a common disorder among CSP and was linked to a higher rate of complications such as foetal death, preterm birth, hysterectomy, haemorrhagic morbidity and surgical complications. Some of the analysed articles showed that sonographic signs with specific characteristics, such as type II and III CSP classification, Crossover Sign - 1, "In the niche" implantation and lower myometrial thickness could be related to worse outcomes of CSP. This article provides a good understanding of CSP as an entity that, although rare, presents with a high rate of relevant morbidity. It is also understood that pregnancies with confirmed PAS had an even higher rate of morbidity. Some sonographic signs were shown to predict the prognosis of these pregnancies and further investigation is necessary to validate one or more signs so they can be used for a more reliable counselling of women with CSP.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Cesarean Section; Premature Birth; Cicatrix; Watchful Waiting; Pregnancy, Ectopic; Pregnancy Outcome; Placenta Accreta; Fetal Death; Retrospective Studies
PubMed: 37421745
DOI: 10.1016/j.ejogrb.2023.06.030 -
The Journal of Maternal-fetal &... Dec 2023To review the usefulness of the sFlt-1/PlGF ratio to detect adverse pregnancy outcomes related to placental dysfunction in twin pregnancies. (Review)
Review
OBJECTIVE
To review the usefulness of the sFlt-1/PlGF ratio to detect adverse pregnancy outcomes related to placental dysfunction in twin pregnancies.
METHODS
A systematic review in Pubmed-Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, and National Guideline was performed. Studies were selected if they were published in the last 10 years, included a sample size equal to or greater than 10 twin gestations, determined the sFlt-1/PIGF ratio, and revealed the pregnancy outcome of the included patients.
RESULTS
A total of 11 studies were selected. Outcomes related to the association between sFlt-1/PlGF ratio throughout pregnancy and perinatal outcome, particularly related to placental dysfunction (early and late-onset preeclampsia and FGR), were collected. The vast majority of studies showed an increased sFlt-1/PlGF ratio in twin pregnancies complicated with preeclampsia or other adverse perinatal outcomes compared with uneventful pregnancies. The included articles revealed promising results when evaluating the usefulness of the sFlt-1/PlGF ratio to rule out preeclampsia. The scarce available data regarding FGR suggests that the sFlt-1/PlGF ratio is a promising tool for detecting this pregnancy complication. Data concerning other aspects of the sFlt-1/PlGF ratio, such as its evolution during healthy twin pregnancies or variations according to chorionicity, is limited.
CONCLUSION
The sFlt-1/PlGF ratio in twin pregnancies is useful to detect, and particularly to rule out adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia or FGR.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Pregnancy, Twin; Placenta Growth Factor; Pre-Eclampsia; Biomarkers; Vascular Endothelial Growth Factor Receptor-1; Placenta
PubMed: 37408114
DOI: 10.1080/14767058.2023.2230514 -
Neural Regeneration Research Nov 2023Although there are challenges in treating traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have recently proven...
Although there are challenges in treating traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have recently proven to be a promising non-cellular therapy. We comprehensively evaluated the efficacy of mesenchymal stem cell-derived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies. Our meta-analysis was registered at PROSPERO (CRD42022327904, May 24, 2022). To fully retrieve the most relevant articles, the following databases were thoroughly searched: PubMed, Web of Science, The Cochrane Library, and Ovid-Embase (up to April 1, 2022). The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool was used to examine the risk of publication bias in animal studies. After screening 2347 studies, 60 studies were included in this study. A meta-analysis was conducted for spinal cord injury (n = 52) and traumatic brain injury (n = 8). The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal cord injury animals, including rat Basso, Beattie and Bresnahan locomotor rating scale scores (standardized mean difference [SMD]: 2.36, 95% confidence interval [CI]: 1.96-2.76, P < 0.01, I = 71%) and mouse Basso Mouse Scale scores (SMD = 2.31, 95% CI: 1.57-3.04, P = 0.01, I = 60%) compared with controls. Further, mesenchymal stem cell-derived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals, including the modified Neurological Severity Score (SMD = -4.48, 95% CI: -6.12 to -2.84, P < 0.01, I = 79%) and Foot Fault Test (SMD = -3.26, 95% CI: -4.09 to -2.42, P = 0.28, I = 21%) compared with controls. Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-derived extracellular vesicles. For Basso, Beattie and Bresnahan locomotor rating scale scores, the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles (allogeneic: SMD = 2.54, 95% CI: 2.05-3.02, P = 0.0116, I = 65.5%; xenogeneic: SMD: 1.78, 95%CI: 1.1-2.45, P = 0.0116, I = 74.6%). Mesenchymal stem cell-derived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultracentrifugation (SMD = 3.58, 95% CI: 2.62-4.53, P < 0.0001, I = 31%) may be more effective than other EV isolation methods. For mouse Basso Mouse Scale scores, placenta-derived mesenchymal stem cell-derived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles (placenta: SMD = 5.25, 95% CI: 2.45-8.06, P = 0.0421, I = 0%; bone marrow: SMD = 1.82, 95% CI: 1.23-2.41, P = 0.0421, I = 0%). For modified Neurological Severity Score, bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs (bone marrow: SMD = -4.86, 95% CI: -6.66 to -3.06, P = 0.0306, I = 81%; adipose: SMD = -2.37, 95% CI: -3.73 to -1.01, P = 0.0306, I = 0%). Intravenous administration (SMD = -5.47, 95% CI: -6.98 to -3.97, P = 0.0002, I = 53.3%) and dose of administration equal to 100 μg (SMD = -5.47, 95% CI: -6.98 to -3.97, P < 0.0001, I = 53.3%) showed better results than other administration routes and doses. The heterogeneity of studies was small, and sensitivity analysis also indicated stable results. Last, the methodological quality of all trials was mostly satisfactory. In conclusion, in the treatment of traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.
PubMed: 37282470
DOI: 10.4103/1673-5374.371376 -
Biology of Reproduction Aug 2023The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the...
The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the subsequent movement of the conceptus to the endometrial cavity. However, when the FT is damaged, as with salpingitis, pyosalpinx, and hydrosalpinx, it may increase the risk of an ectopic pregnancy, a life-threatening condition. Decidualization refers to a multifactorial process by which the endometrium changes to permit blastocyst implantation. The decidualization reaction is vital for endometrial receptivity during the window of implantation. To date, no comprehensive review that collates evidence on decidualization in the human FT has been conducted. Therefore, the aim of this review is to compile the current evidence on cellular decidualization occurring in the healthy and pathological FT in women of reproductive age. A literature search was conducted using five databases and identified 746 articles, 24 of which were analyzed based on inclusion and exclusion criteria. The available evidence indicates that the FT are able to undergo decidual changes under specific circumstances; however, the exact mechanism by which this occurs is poorly understood. Further research is needed to elucidate the mechanism by which decidualization can occur in the FT.
Topics: Pregnancy; Female; Humans; Fallopian Tubes; Endometrium; Embryo Implantation; Uterus; Decidua; Stromal Cells
PubMed: 37265359
DOI: 10.1093/biolre/ioad062 -
American Journal of Obstetrics &... Aug 2023This systematic review and meta-analysis aimed to assess clinical characteristics related to pathologically proven placenta accreta spectrum without placenta previa. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis aimed to assess clinical characteristics related to pathologically proven placenta accreta spectrum without placenta previa.
DATA SOURCES
A literature search of PubMed, the Cochrane database, and Web of Science was performed from inception to September 7, 2022.
STUDY ELIGIBILITY CRITERIA
The primary outcomes were invasive placenta (including increta or percreta), blood loss, hysterectomy, and antenatal diagnosis. In addition, maternal age, assisted reproductive technology, previous cesarean delivery, and previous uterine procedures were investigated as potential risk factors. The inclusion criteria were studies evaluating the clinical presentation of pathologically diagnosed PAS without placenta previa.
METHODS
Study screening was conducted after duplicates were identified and removed. The quality of each study and the publication bias were assessed. Forest plots and I statistics were calculated for each study outcome for each group. The main analysis was a random-effects analysis.
RESULTS
Among 2598 studies that were initially retrieved, 5 were included in the review. With the exception of 1 study, 4 studies were included in the meta-analysis. This meta-analysis showed that placenta accreta spectrum without placenta previa was associated with less risk of invasive placenta (odds ratio, 0.24; 95% confidence interval, 0.16-0.37), blood loss (mean difference, -1.19; 95% confidence interval, -2.09 to -0.28) and hysterectomy (odds ratio, 0.11; 95% confidence interval, 0.02-0.53), and more difficult to diagnose prenatally (odds ratio, 0.13; 95% confidence interval, 0.04-0.45) than placenta accreta spectrum with placenta previa. In addition, assisted reproductive technology and a previous uterine procedure were strong risk factors for placenta accreta spectrum without placenta previa, whhereas previous cesarean delivery was a strong risk factor for placenta accreta spectrum with placenta previa.
CONCLUSION
The differences in clinical aspects of placenta accreta spectrum with and without placenta previa need to be understood.
Topics: Pregnancy; Female; Humans; Placenta Accreta; Retrospective Studies; Placenta Previa; Hysterectomy; Risk Factors
PubMed: 37211089
DOI: 10.1016/j.ajogmf.2023.101027 -
Human Reproduction Update Sep 2023The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness.
OBJECTIVE AND RATIONALE
The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET.
SEARCH METHODS
A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2.
OUTCOMES
The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from low to high, while quality of the evidence was very low to moderate.
WIDER IMPLICATIONS
This study confirms that NC-FET decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. We estimate that for each adverse outcome, use of NC-FET may prevent 4 to 22 cases per 1000 women. Consequently, NC-FET should be the preferred treatment in women with ovulatory cycles undergoing FET. Based on very low quality of evidence, the risk of preterm birth be decreased when LPS is used in NC-FET compared to AC-FET. However, because of many uncertainties-the major being the debate about efficacy of the use of LPS-future research is needed on efficacy and safety of LPS and no recommendation can be made about the use of LPS.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Birth Weight; Premature Birth; Luteal Phase; Lipopolysaccharides; Cryopreservation; Embryo Transfer; Pregnancy Rate; Retrospective Studies
PubMed: 37172270
DOI: 10.1093/humupd/dmad011 -
Archivos Argentinos de Pediatria Oct 2023Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated...
Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders. A systematic search of the MEDLINE and ScienceDirect databases was conducted; the results were presented in tables and narrative synthesis. Only 31 studies met the eligibility criteria. Overall, the evidence on the effects of mercury exposure and neurodevelopmental disorders in children is limited. Learning disabilities, autism, and attention deficit hyperactivity disorder were some of the reported potential effects.
Topics: Pregnancy; Female; Child; Humans; Mercury; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Autistic Disorder
PubMed: 37145892
DOI: 10.5546/aap.2022-02838.eng -
American Journal of Obstetrics and... Aug 2023This study aimed to describe the characteristics of fetal demise after SARS-CoV-2 infections and clarify whether it is associated with clinical severity, placental... (Review)
Review
OBJECTIVE
This study aimed to describe the characteristics of fetal demise after SARS-CoV-2 infections and clarify whether it is associated with clinical severity, placental lesions, or malformations or due to actual fetal infections.
DATA SOURCES
PubMed and Web of Science databases were searched between December 1, 2019, and April 30, 2022.
STUDY ELIGIBILITY CRITERIA
Cohort, cross-sectional, and case-control studies and case series or case reports describing stillbirths or late miscarriages (ie, pregnancy loss occurring between 14 and 22 weeks of gestation, before and after the onset of labor) from mothers with SARS-CoV-2 infection during pregnancy (demonstrated by at least 1 positive real-time reverse transcription-polymerase chain reaction from nasopharyngeal swabs and/or SARS-CoV-2 placental infection). No language restriction was applied; cases with other causes possibly explaining the fetal demise were excluded.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines were followed. The quality of the case series and case reports was evaluated using the specific Mayo Clinic Evidence-Based Practice Center tool. Maternal and clinical fetal data and placental and fetal virology and histology findings were collected. Data were summarized with descriptive statistics using the World Health Organization criteria to classify disease severity and fetal-neonatal infections.
RESULTS
Data from 184 mothers and 190 fetuses were analyzed. No clear link to maternal clinical severity or fetal malformation was evident. Approximately 78% of fetal demise cases occurred during the second and third trimesters of pregnancy, approximately 6 to 13 days after the diagnosis of SARS-CoV-2 infection or the onset of symptoms. Most placentas (88%) were positive for SARS-CoV-2 or presented the histologic features of placentitis (massive fibrin deposition and chronic intervillositis) previously observed in transplacentally transmitted infections (85%-91%). Of note, 11 fetuses (5.8%) had a confirmed in utero transmitted SARS-CoV-2 infection, and 114 fetuses (60%) had a possible in utero transmitted SARS-CoV-2 infection.
CONCLUSION
The synthesis of available data showed that fetal demise generally occurs a few days after the infection with histologic placental inflammatory lesions associated with transplacental SARS-CoV-2 transmission and eventually causing placental insufficiency.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; COVID-19; Cross-Sectional Studies; Fetal Death; Infectious Disease Transmission, Vertical; Placenta; Pregnancy Complications, Infectious; SARS-CoV-2; Stillbirth
PubMed: 36706855
DOI: 10.1016/j.ajog.2023.01.019 -
Epigenetics Dec 2023Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future...
Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.
Topics: Pregnancy; Humans; Infant, Newborn; Female; Pregnancy Trimester, First; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Circulating MicroRNA; Placenta; Premature Birth; DNA Methylation; MicroRNAs; Pregnancy Complications; Placentation; Biomarkers
PubMed: 36503407
DOI: 10.1080/15592294.2022.2152615