MRI Assessed Placental Location as a Diagnostic Tool of Placental Invasiveness and Maternal Peripartum Morbidity.

Placenta accreta spectrum (PAS) disorder is one of the leading causes of peripartum maternal morbidity and mortality; its early identification during pregnancy is of utmost importance to ensure the optimal clinical outcome. The aim of the present study is to investigate the possible association of the presence and type/location of placenta previa on MRI with PAS and maternal peripartum outcome. One hundred eighty-nine pregnant women (mean age: 35 years; mean gestational age: 32 weeks) at high risk for PAS underwent a dedicated placental MRI. All women underwent a C-section within 6 weeks from the MRI. All MRIs were evaluated by two experienced genitourinary radiologists for presence, type (complete/partial vs. marginal/low lying), and location (anterior vs. anterior-posterior vs. posterior) of placenta previa. Statistical analysis was performed for possible association of type/location of previa with placental invasiveness and peripartum outcomes. Intraoperative information was used as a reference standard. Complete/partial previa was detected in 143/189 (75.6%) and marginal/low lying previa in 33/189 (17.5%) women; in 88/189 (46.6%) women, the placenta had anterior-posterior, in 54/189 (28.6%) anterior and in 41/189 (21.7%) posterior. Complete/partial previa had an at least 3-fold probability of invasiveness and was more frequently associated with unfavorable peripartum events, including massive intraoperative blood loss or hysterectomy, compared to low-lying/marginal placenta. Posterior placental location was significantly associated with lower rates of PAS and better clinical outcomes. In conclusion, the type and location of placenta previa shown with MRI seems to be associated with severity of complications during delivery and should be carefully studied.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Persistent Postpartum Urinary Retention: A Case Report and Review of Literature.

This case report describes persistent urinary retention lasting over 30 days postpartum in a 23-year-old primiparous female after an otherwise uncomplicated vaginal delivery at 37 weeks gestation. Notable risk factors present included epidural anesthesia, episiotomy, third-degree perineal laceration, and inability to void spontaneously before leaving the delivery room. Despite initial catheterization draining a large volume, the patient experienced recurrent failed voiding trials requiring ongoing intermittent catheterization during her admission. One month after delivery, voiding trials were finally successful, and she regained normal spontaneous voiding without catheterization. This case highlights persistent postpartum urinary retention (PUR) as an uncommon but potentially serious obstetric complication requiring prompt diagnosis and appropriate management to prevent adverse events and optimize outcomes. Although most cases are self-limited, a high index of suspicion is needed to institute timely treatment with intermittent catheterization given the morbidity associated with sustained bladder overdistension postpartum.

Cracking the Code: Investigating the Correlation between Aerobic Vaginitis and Preterm Labor.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which has a range of 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. An improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Prospective Study on the Correlation between CART and Leptin Gene Expression, Obesity, and Reproductive Hormones in Individuals Undergoing Bariatric Surgery.

Obesity, a global health concern affecting 650 million individuals of all ages worldwide, prompts health complications, including fertility issues. This research investigates the impact of bariatric surgery on morbidly obese females under 40, examining the relationship between CART and leptin gene expressions and reproductive hormones. Post-surgery, a significant reduction in BMI (16.03 kg/m2, n = 29) was observed, accompanied by notable hormonal changes. FSH levels showed a mean difference of 3.18 ± 1.19 pre- and post-surgery (p < 0.001), LH levels exhibited a mean difference of 2.62 ± 1.1 (p < 0.001), E2 levels demonstrated a mean difference of 18.62 ± 5.02 (p < 0.001), and AMH levels showed a mean difference of 3.18 ± 1.19 (p < 0.001). High CART and leptin expressions before treatment correlated with lower expressions after treatment. These findings, rooted in statistically significant correlations (CART: rs = 0.51, p = 0.005; leptin: rs = 0.75, p < 0.001), shed light on potential molecular pathways connecting gene expressions with reproductive hormones post-bariatric surgery. Our study uniquely investigates the interplay between genetic markers, infertility, and bariatric surgery in women. It stands out by providing distinctive insights into the development of personalized treatment strategies for obesity-related infertility, contributing to a deeper understanding of this complex medical issue.

The prognostic role of CRL discordance in first trimester ultrasound.

OBJECTIVES: In the first trimester, intertwin crown-rump length (CRL) discordance has emerged as a notable factor linked to adverse perinatal health effects. It is frequently employed as a basis for counseling parents regarding potential adverse pregnancy outcomes. Despite its established association with adverse outcomes, the significance of CRL discordance in substantially predicting pregnancy problems and its efficacy in pregnancy screening remain subjects of ongoing discussion. The aim of this manuscript is to present current knowledge on CRL discordance. METHODS: PubMed was searched for related articles with terms "Crown-Rump length", "Prenatal Screening", "Twin pregnancy", "Discordance". RESULTS: Twenty-two studies were included in our study with six reporting data on monochorionic and 16 assessing the correlation between CRL discordance and adverse pregnancy outcomes. Fetal loss at the 20th and 24th week of the pregnancy, SGA neonates, pre-term delivery (32 weeks), perinatal death (24 weeks) are all reported adverse outcomes associated with CRL discordance. The reported cut-off for increased risk of adverse perinatal outcomes is a discordance of at least 10% or more. CONCLUSIONS: Increased CRL (>10 %) discordance is linked to a higher risk of sFGR in both monochorionic and dichorionic pregnancies, fetal loss, and preterm delivery.

Choriocarcinoma After Term Pregnancy With a Subsequent Successful Pregnancy: A Rare Entity.

Gestational trophoblastic neoplasia (GTN) is a group of pregnancy-related disorders that arise from the cells of conception. They include gestational choriocarcinoma (CC), placental site trophoblastic tumor, and epithelioid trophoblastic tumor with these forms arising from a molar pregnancy, abortion, or a normal genetic pregnancy. Most cases of GTN are diagnosed when the serum hCG levels plateau or rise in patients being followed up after the diagnosis of hydatidiform mole but can also be suspected due to persistent vaginal bleeding after a normal pregnancy and delivery. Early diagnosis and treatment are pivotal for ensuring optimal outcomes and given the rarity of the disease, clinical management and treatment should be provided in specialized centers. Here, we present a rare case of a 31-year-old woman diagnosed with choriocarcinoma with pulmonary metastasis following an uncomplicated full-term pregnancy. After the suction evacuation and curettage, she underwent six cycles of chemotherapy with an excellent response, a fact that resulted in a subsequent pregnancy and birth without complications, occurring 18 months thereafter.

The role of the PLGF in the prediction of the outcome in pregnancies with a small for gestational age fetus.

PURPOSE: To explore the value of measuring maternal serum PLGF in the prediction of the outcome of small for gestational age fetuses (SGA). METHODS: Singleton pregnancies referred with suspicion of SGA in the third trimester were included if they had: no indication for nor signs of imminent delivery, fetal abdominal circumference (AC) at or below the 10th centile and/or estimated fetal weight (EFW) at or below the 10th centile and/or umbilical artery pulsatility index (Umb-PI) at or above the 90th centile for gestation. Women with pre-eclampsia at presentation were excluded. Maternal blood was drawn at the first (index) visit and analyzed retrospectively. RESULTS: Fifty-one fetuses were examined. Multiple regression analysis showed that family history of microsomia, index EFW and PLGF were significant predictors of the birthweight centile; index femur length centile and PLGF were significant predictors of pre-eclampsia; PLGF and index systolic blood pressure were significant predictors of iatrogenic preterm delivery < 37 weeks, whereas PLGF and index EFW were significant predictors of birthweight ≤ 5th centile and admission to the neonatal intensive care unit. For all outcomes, the addition of maternal-fetal parameters did not improve the prediction compared to PLGF alone. Using a cutoff of 0.3 MoM for PLGF would identify 94.1% of the pregnancies with iatrogenic preterm delivery and/or intra-uterine death and all of the cases that developed pre-eclampsia, for a screen positive rate of 54.9%. Women with PLGF ≤ 0.3 MoM had a poor fetal/maternal outcome (iatrogenic preterm delivery, pre-eclampsia, intra-uterine death) in 61.5% of cases. CONCLUSION: In pregnancies complicated by SGA, PLGF identifies a very high-risk group that may benefit from intense surveillance.

Congenital Heart Block and Its Association With Anti-Ro and Anti-La Antibodies in Pregnancy: A Case Report of a Rare Entity and a Review of the Current Evidence.

Systemic lupus erythematosus (SLE) is a heterogeneous chronic, multisystem, inflammatory autoimmune disorder with variable clinical features, with its manifestations being attributed to the presence of multiple autoantibodies and their subsequent autoimmune reactions. Multiple organs may be involved, with the kidneys, the joints, and the skin being the most common, increasing maternal and fetal morbidity and mortality. Our current article describes the case of a 32-year-old primigravida who was referred to our department after the detection of fetal bradycardia and the strong suspicion of an underlying cardiac abnormality. After a detailed fetal and maternal assessment, the diagnosis of SLE-associated fetal congenital heart block was established, and the appropriate management and treatment were provided, factors that led to the uncomplicated delivery and prompt successful management of an otherwise severely affected fetus. Our work, also, includes a detailed review of the accumulated evidence regarding the association between autoantibodies and congenital heart block, the available screening modalities of the condition, and its potential therapeutic interventions.

The correlation between transient osteoporosis of the hip and pregnancy: A review.

Transient osteoporosis of the hip is indubitably a comparatively infrequent entity affecting both men and women worldwide. Its occurrence in the course of pregnancy, specifically in the third trimester, and lactation are of paramount concernment. The exact association between transient hip osteoporosis and pregnancy is precarious. Etiology and potential pathophysiological mechanisms behind this correlation are still to be utterly defined. Magnetic resonance imaging is highly regarded as the gold standard imaging method for assiduous assessment of this disorder. Physicians of copious medical specialties should practice scrupulous techniques for early and pertinent diagnosis when pregnant women are presented with persistent hip pain, as differential diagnosis with femoral head avascular necrosis can be exceedingly arduous. Treatment is predominantly conservative with protected weight-bearing and analgesic medication in the first line of management. In terms of prognosis, the disease ordinarily resolves spontaneously after a few months. Further research is required in order to elucidate the ambiguity surrounding the establishment of globally approved diagnosis and treatment guidelines for pregnancy-associated transient hip osteoporosis. This paper aims to accentuate the significance of this particular disorder by providing a succinct review of the existing literature, augmenting clinicians' knowledge about the features of pregnancy-related transient proximal femur osteoporosis.

MicroRNAs Can Influence Ovarian Cancer Progression by Dysregulating Integrin Activity.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Bladder Cancer during Pregnancy: A Review of the Literature.

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5-1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

First trimester maternal plasma proteomic changes predictive of spontaneous moderate/late preterm delivery.

OBJECTIVE: Identification of differentially expressed proteins (DEPs) in first trimester maternal plasma between pregnant women with a subsequent spontaneous moderate/late Preterm Delivery (sPTD) and women who delivered at term. The sPTD group consisted of women who delivered between 32°/7 and 366/7 weeks of gestation. METHODS: Isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS was used for the analysis of five first trimester maternal plasma samples obtained from women with a subsequent moderate/late preterm sPTD and five women with term deliveries. Enzyme-linked immunosorbent assay (ELISA) was further applied in an independent cohort of 29 sPTD cases and 29 controls to verify the expression levels of selected proteins. RESULTS: 236 DEPs, mainly linked to coagulation and complement cascade, were identified in first trimester maternal plasma obtained from the sPTD group. Decreased levels of selected proteins, namely, VCAM-1, SAA, and Talin-1, were further confirmed using ELISA, highlighting their potential as candidate predictive biomarkers for sPTD at32°/7 and 366/7 weeks of gestation. CONCLUSION: First trimester maternal plasma proteomic analysis revealed protein changes associated with subsequent moderate/late preterm sPTD.

Intrauterine Growth Restriction Due to Gestational Diabetes: From Pathophysiology to Diagnosis and Management.

Intrauterine growth restriction (IUGR) represents a condition where the fetal weight is less than the 10th percentile for gestational age, or the estimated fetal weight is lower than expected based on gestational age. IUGR can be caused by various factors such as maternal, placental or fetal factors and can lead to various complications for both the fetus and the mother, including fetal distress, stillbirth, preterm delivery, and maternal hypertension. Women with gestational diabetes are at an increased risk of developing IUGR. This article reviews the different aspects of gestational diabetes in addition to IUGR, the diagnostic methods available for IUGR detection, including ultrasound and Doppler studies, discusses the management strategies for women with IUGR and gestational diabetes and analyzes the importance of early detection and timely intervention to improve pregnancy outcomes.

Expression of Stemness Markers in the Cervical Smear of Patients with Cervical Insufficiency.

The presence of stem cells has been previously described in human precancerous and malignant cervical cultures. Previous studies have shown a direct interplay of the stem cell niche, which is present in practically every tissue with the extracellular matrix. In the present study, we sought to determine the expression of stemness markers in cytological specimens collected from the ectocervix among women with cervical insufficiency during the second trimester of pregnancy and women with normal cervical length. A prospective cohort of 59 women was enrolled of whom 41 were diagnosed with cervical insufficiency. The expression of OCT-4 and NANOG was higher in the cervical insufficiency group compared to the control group (-5.03 (-6.27, -3.72) vs. -5.81 (-7.67, -5.02) p = 0.040 for OCT4) and (-7.47 (-8.78, -6.27) vs. -8.5 (-10.75, -7.14), p = 0.035 for NANOG. Differences in the DAZL gene were not significantly different (5.94 (4.82, 7.14) vs. 6.98 (5.87, 7.43) p = 0.097). Pearson correlation analysis indicated the existence of a moderate correlation of OCT-4 and Nanog with cervical length. Considering this information, the enhanced activity of stemness biomarkers among pregnant women diagnosed with cervical insufficiency may be predisposed to cervical insufficiency, and its predictive accuracy remains to be noted in larger population sizes.

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications.

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

Inflammatory Molecules Responsible for Length Shortening and Preterm Birth.

It is estimated that inflammation at the placental-maternal interface is directly responsible for or contributes to the development of 50% of all premature deliveries. Chorioamnionitis, also known as the premature rupture of the amniotic membrane in the mother, is the root cause of persistent inflammation that preterm newborns experience. Beyond contributing to the onset of early labor, inflammation is a critical element in advancing several conditions in neonates, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity and periventricular leukomalacia. Notably, the immune systems of preterm infants are not fully developed; immune defense mechanisms and immunosuppression (tolerance) have a delicate balance that is easily upset in this patient category. As a result, premature infants are exposed to different antigens from elements such as hospital-specific microbes, artificial devices, medications, food antigens and hypoxia/hyperoxia. This has detrimental implications for preterm deliveries of less than 28 weeks because they have not yet evolved the mechanisms to tolerate maternal and self-antigens.

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.

of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6 weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6 weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6 weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6 weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0 weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0 weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

Efficacy and safety of oral and sublingual versus vaginal misoprostol for induction of labour: a systematic review and meta-analysis.

OBJECTIVE: Misoprostol is a synthetic PGE1 analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit maternal and neonatal adverse outcomes. The present meta-analysis investigates the efficacy and safety of oral compared to vaginally inserted misoprostol in terms of induction of labor and adverse peripartum outcomes. METHODS: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till April 2022. Randomized controlled trials that assessed the efficacy of oral misoprostol (per os or sublingual) compared to vaginally inserted misoprostol. Effect sizes were calculated in R. Sensitivity analysis was performed to evaluate the possibility of small study effects, p-hacking. Meta-regression and subgroup analysis according to the dose of misoprostol was also investigated. The methodological quality of the included studies was assessed by two independent reviewers using the risk of bias 2 tool. Quality of evidence for primary outcomes was evaluated under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, ranging from very low to high. RESULTS: Overall, 57 studies were included that involved 10,975 parturient. Their risk of bias ranged between low-moderate. There were no differences among the routes of intake in terms of successful vaginal delivery within 24 h (RR 0.90, 95% CI 0.80) and cesarean section rates (RR 0.92, 95% CI 0.82, 1.04). Sublingual misoprostol was superior compared to vaginal misoprostol in reducing the interval from induction to delivery (MD - 1.11 h, 95% CI - 2.06, - 0.17). On the other hand, per os misoprostol was inferior compared to vaginal misoprostol in terms of this outcome (MD 3.45 h, 95% CI 1.85, 5.06). Maternal and neonatal morbidity was not affected by the route or dose of misoprostol. CONCLUSION: The findings of our study suggest that oral misoprostol intake is equally safe to vaginal misoprostol in terms of inducing labor at term. Sublingual intake seems to outperform the per os and vaginal routes without increasing the accompanying morbidity. Increasing the dose of misoprostol does not seem to increase its efficacy. CLINICAL TRIAL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/V9JHF ).