Randomized trials have found benefits of both vaginal progesterone and 17-alpha-hydroxyprogesterone caproate in the prevention of recurrent preterm birth. A previous meta-analysis directly comparing the two was limited by low-quality evidence, and national and international society guidelines remain conflicting regarding progestin formulation recommended for prevention of recurrent preterm birth. The aim of this updated systematic review with meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-alpha-hydroxyprogesterone caproate in the prevention of spontaneous preterm birth in patients with singleton gestations and previous spontaneous preterm birth.
Searches were performed in MEDLINE, Ovid, Scopus, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews (PROSPERO), SciELO, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) with the use of a combination of keywords and text words related to \"preterm birth,\" \"preterm delivery,\" \"singleton,\" \"cervical length,\" \"progesterone,\" \"progestogens,\" \"vaginal,\" \"17-alpha-hydroxy-progesterone caproate,\" and \"intramuscular\" from inception of each database to September 2021. No restrictions for language or geographic location were applied.
We included all randomized controlled trials of asymptomatic singleton gestations with previous spontaneous preterm birth that were randomized to prophylactic treatment with either vaginal progesterone (ie, intervention group) or intramuscular 17-alpha-hydroxyprogesterone caproate (ie, comparison group). Post hoc sensitivity analysis was performed for studies with low risk of bias and studies with protocol registration.
The primary outcome was preterm birth <34 weeks\' gestation. The summary measures were reported as relative risks with 95% confidence intervals.
Seven randomized controlled trials including 1910 patients were included in the meta-analysis. Patients who received vaginal progesterone had a significantly lower rate of preterm birth at <34 weeks (14.7% vs 19.9%; relative risk, 0.74; 95% confidence interval, 0.57-0.96), preterm birth at <37 weeks (36.0% vs 46.6%; relative risk, 0.76; 95% confidence interval, 0.69-0.85), and preterm birth at <32 weeks of gestation (7.9% vs 13.6%; relative risk, 0.58; 95% confidence interval, 0.39-0.86), compared with women who received intramuscular 17-alpha-hydroxyprogesterone caproate. There were no significant differences in the rate of preterm birth at <28 weeks\' gestation. Adverse drug reactions were significantly lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (15.6% vs 22.2%; relative risk, 0.71; 95% confidence interval, 0.54-0.92). Perinatal mortality was lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (2.2% vs 4.4%; relative risk, 0.51; 95% confidence interval, 0.25-1.01). In sensitivity analysis including trials rated with at least 4 Cochrane tools as of \"low risk of bias,\" 4 trials were included (N=575), and there was no longer a significant difference in preterm birth at <34 weeks\' gestation between vaginal progesterone and 17-alpha-hydroxyprogesterone caproate (12.2% vs 13.9%; relative risk, 0.87; 95% confidence interval, 0.57-1.32).
Overall, vaginal progesterone was superior to 17-alpha-hydroxyprogesterone caproate in the prevention of preterm birth at <34 weeks\' gestation in singleton pregnancies with previous spontaneous preterm birth. Although sensitivity analysis of high-fidelity studies showed the same trend, findings were no longer statistically significant.

OBJECTIVE: We aimed to predict the perinatal outcomes and costs of health services following labour induction for late-term pregnancies.
METHODS: We conducted a cohort study of 245 women who underwent labour induction during their 41st week of gestation. The cervical condition was assessed upon admission using the Bishop score and ultrasound cervical length measurements. We estimated the direct costs of labour induction, and a predictive model for perinatal outcomes was constructed using the decision tree analysis algorithm and a logit model.
RESULTS: A very unfavourable Bishop score at admission (Bishop score <2) (OR, 3.43 [95% CI, 1.77-6.59]), and a history of previous caesarean section (OR, 7.72 [95% CI, 2.43-24.43]) or previous vaginal delivery (OR, 0.24 [95% CI, 0.09-0.58]) were the only variables with predictive capacity for caesarean section in our model. The mean cost of labour induction was €3465.56 (95% confidence interval [CI], 3339.53-3591.58). Unfavourable Bishop scores upon admission and no history of previous deliveries significantly increased the cost of labour induction. Both of these criteria significantly predicted the likelihood of a caesarean section in the decision tree analysis.
CONCLUSIONS: The cost of labour induction mostly depends on the likelihood of successful trial of labour. Combined use of the Bishop score and previous vaginal or caesarean deliveries improves the ability to predict the likelihood of a caesarean section and the economic costs associated with labour induction for late-term pregnancies. This information is useful for patient counselling.

OBJECTIVE: To assess the predictive value of sonographic cervical-length (CL) measurement in mid-gestation for spontaneous preterm birth (PTB) in asymptomatic triplet pregnancy.
METHODS: This was a retrospective study of asymptomatic triplet pregnancies followed at five Italian tertiary referral centers, between 2002 and 2015. CL was measured transvaginally between 18 and 24 weeks\' gestation. Pregnancies with medically indicated PTB were excluded. Demographic and pregnancy characteristics of pregnancies complicated by PTB were analyzed and the distributions of CL measurements in these patients were calculated. Logistic regression analysis was performed to assess the association between CL and PTB, adjusted for confounders. Performance of CL measurement in prediction of PTB < 28, < 30 and < 32 weeks of gestation was assessed.
RESULTS: A total of 120 triplet pregnancies were included in the final analysis. Median CL was 35 (interquartile range (IQR), 29-40) mm measured at a median gestational age of 20 + 2 (IQR, 20 + 0 to 23 + 4) weeks. Overall, 23 (19.2%), 17 (14.2%) and eight (6.7%) patients had a CL < 25, < 20 and < 15 mm, respectively. Spontaneous PTB < 32 weeks occurred in 41 (34.2%) cases, < 30 weeks in 23 (19.2%) and < 28 weeks in 12 (10%) cases. CL < 15 mm was significantly more frequent in the group of patients who delivered < 28 (P = 0.03) and < 30 (P = 0.01) weeks\' gestation, compared with those who delivered after 28 and after 30 weeks, respectively, while CL < 20 mm was more common in triplet pregnancies with delivery < 32 weeks compared with those delivered ≥ 32 weeks (P = 0.03). Logistic regression analysis was possible only for PTB < 32 weeks due to the small number of cases that delivered < 30 and < 28 weeks. After adjustment for confounders, CL was not significantly associated with PTB < 32 weeks (adjusted odds ratio, 0.97; 95% CI, 0.94-1.01). CL measurement had an area under the receiver-operating characteristics curve of 0.41 (95% CI, 0.20-0.62), 0.41 (95% CI, 0.26-0.56) and 0.42 (95% CI, 0.31-0.54) for the prediction of spontaneous PTB < 28, < 30 and < 32 weeks, respectively.
CONCLUSIONS: CL assessed in mid-gestation is a poor predictor of PTB < 28, < 30 and < 32 weeks\' gestation in asymptomatic triplet pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

In France, 60,000 neonates are born preterm every year (7.4%), half of them after the spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated with decreased prematurity (level of evidence [LE]1). It is therefore recommended (Grade A). Routine screening and treatment of vaginal bacteriosis is not recommended in the general population (Grade A). The only population for which vaginal progesterone is recommended is that comprising asymptomatic women with singleton pregnancies, no history of preterm delivery, and a short cervix at 16-24 weeks of gestation (Grade B). A history-indicated cerclage is not recommended for women with only a history of conization (Grade C), uterine malformation (professional consensus), isolated history of preterm delivery (Grade B), or twin pregnancies for primary (Grade B) or secondary (Grade C) prevention of preterm birth. A history-indicated cerclage is recommended for a singleton pregnancy with a history of at least 3 late miscarriages or preterm deliveries (Grade A). Ultrasound cervical length screening is recommended between 16 and 22 weeks for women with a singleton previously delivered before 34 weeks gestation, so that cerclage can be offered if cervical length <25mm before 24 weeks (Grade C). A cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with twin pregnancies (Grade A) or in populations of asymptomatic women with a short cervix (professional consensus). Although the implementation of universal screening by transvaginal ultrasound for cervical length at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In cases of preterm labor, (i) it is not possible to recommend any one of the several methods (ultrasound of the cervical length, vaginal examination, or fetal fibronectin assay) over any other to predict preterm birth (Grade B); (ii) routine antibiotic therapy is not recommended (Grade A); (iii) prolonged hospitalization (Grade B) and bed rest (Grade C) are not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (Grade B), unlike beta-agonists (Grade C), can be used for tocolysis in spontaneous preterm labor without preterm premature rupture of membranes. Maintenance tocolysis is not recommended (Grade B). Antenatal corticosteroid administration is recommended for all women at risk of preterm delivery before 34 weeks of gestation (Grade A). After 34 weeks, the evidence is insufficiently consistent to justify recommending systematic antenatal corticosteroid treatment (Grade B), but a course of this treatment might be indicated in clinical situations associated with high risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (Grade C). Repeated courses of antenatal corticosteroids are not recommended (Grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended for women at high risk of imminent preterm birth before 32 weeks (Grade A). Cesareans are not recommended for fetuses in vertex presentation (professional consensus). Both planned vaginal and elective cesarean delivery are possible for breech presentations (professional consensus). Delayed cord clamping may be considered if the neonatal or maternal state allows (professional consensus).

OBJECTIVE: To determine the measures to prevent spontaneous preterm birth (excluding preterm premature rupture of membranes)and its consequences.
METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted.
RESULTS: In France, premature birth concerns 60,000 neonates every year (7.4 %), half of them are delivered after spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated to a decrease of prematurity (level of evidence [LE] 1). This is therefore recommended (grade A). Routine screening and treatment of vaginal bacteriosis in general population is not recommended (grade A). Asymptomatic women with single pregnancy without history of preterm delivery and a short cervix between 16 and 24 weeks is the only population in which vaginal progesterone is recommended (grade B). A history-indicated cerclage is not recommended in case of only past history of conisation (grade C), uterine malformation (Professional consensus), isolated history of pretem delivery (grade B) or twin pregnancies in primary (grade B) or secondary (grade C) prevention of preterm birth. A history-indicated cerclage is recommended for single pregnancy with a history of at least 3 late miscarriages or preterm deliveries (grade A).). In case of past history of a single pregnancy delivery before 34 weeks gestation (WG), ultrasound cervical length screening is recommended between 16 and 22 WG in order to propose a cerclage in case of length<25mm before 24 WG (grade C). Cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with a twin pregnancy (grade A) and in populations of asymptomatic women with a short cervix (Professional consensus). Although the implementation of a universal transvaginal cervical length screening at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In case of preterm labor, (i) it is not possible to recommend one of the methods over another (ultrasound of the cervical length, vaginal examination, fetal fibronectin) to predict preterm birth (grade B); (ii) routine antibiotic therapy is not recommended (grade A); (iii) prolonged hospitalization (grade B) and bed rest (grade C) is not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (grade B), contrary to betamimetics (grade C), can be used for tocolysis in spontaneous preterm labour without preterm premature rupture of membranes. Maintenance tocolysis is not recomended (grade B). Antenatal corticosteroid administration is recommended to every woman at risk of preterm delivery before 34 weeks of gestation (grade A). After 34 weeks, evidences are not consistent enough to recommend systematic antenatal corticosteroid treatment (grade B), however, a course might be indicated in the clinical situations associated with the higher risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (grade C). Repeated courses of antenatal corticosteroids are not recommended (grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended to women at high risk of imminent preterm birth before 32WG (grade A). Cesarean is not recommended in case of vertex presentation (Professional consensus). Both planned vaginal or elective cesarean delivery is possible in case of breech presentation (Professional consensus). A delayed cord clamping may be considered if the neonatal or maternal state so permits (Professional consensus).
CONCLUSIONS: Except for antenatal corticosteroid and magnesium sulfate administration, diagnostic tools or prenatal pharmacological treatments implemented since 30 years to prevent preterm birth and its consequences have not matched expectations of caregivers and families.

OBJECTIVE: Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB.
METHODS: Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed.
RESULTS: Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53-0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40-0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0.53 (95% CI, 0.31-0.91); very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared with 17-OHPC (18.7% vs 23.5%; RR, 0.63 (95% CI, 0.47-0.83); low quality of evidence). For the comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was not reached) and by at least one degree due to indirectness (different interventions).
CONCLUSIONS: Daily vaginal progesterone (either suppository or gel) started at about 16 weeks\' gestation is a reasonable, if not better, alternative to weekly 17-OHPC injection for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low or very low as assessed by GRADE, indicating that the true effect may be, or is likely to be, substantially different from the estimate of the effect. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. COMPARACIÓN ENTRE LA PROGESTERONA VAGINAL Y EL 17Α-HIDROXIPROGESTERONA CAPROATO INTRAMUSCULAR PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO ESPONTÁNEO RECURRENTE EN EMBARAZOS CON FETO ÚNICO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIOS: RESUMEN OBJETIVO: Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en inglés) por vía intramuscular con la progesterona por vía vaginal para la reducción del riesgo de parto pretérmino espontáneo (PPTE) en embarazos con feto único de gestantes con historial de PPTE. El objetivo de esta revisión sistemática y metaanálisis fue evaluar la eficacia de la progesterona vaginal en comparación con la 17-OHPC en la prevención de embarazos con feto único de gestantes con historial de PPTE. MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas para identificar todos los ECA con embarazos de feto único asintomáticos con historial de PPTE antes de ser asignados al azar a un tratamiento profiláctico, ya fuera con progesterona vaginal (grupo de intervención) o con 17-OHPC intramuscular (grupo de control). No se aplicaron restricciones respecto al idioma o la ubicación geográfica. El resultado primario fue PPTE < 34 semanas. Los resultados secundarios fueron PPTE <37 semanas, < 32 semanas, < 28 semanas y < 24 semanas, la reacción materna adversa al fármaco y los resultados neonatales. Las medidas del resumen se reportaron como riesgo relativo (RR) con IC del 95%. Para cada estudio incluido se evaluó el riesgo de sesgo.
UNASSIGNED: Se incluyeron tres ECA (680 mujeres). La media de la edad gestacional en el momento de la aleatorización fue de 16 semanas. A las mujeres se les administró progesterona hasta la semana 36 o hasta el parto. Con respecto a la progesterona vaginal, un estudio utilizó gel de 90 mg diariamente, otro utilizó un supositorio diario de 100 mg y el otro utilizó un supositorio diario de 200 mg. Todos los ECA incluidos en el grupo de comparación utilizaron 250 mg semanales de 17-OHPC por vía intramuscular. Las mujeres que recibieron progesterona vaginal tuvieron tasas significativamente más bajas de PPTE < 34 semanas (17,5% vs. 25,0%; RR 0,71 (IC 95%, 0,53-0,95); calidad de la evidencia baja) y < 32 semanas (8,9% vs. 14,5%; RR 0,62 (IC 95%, 0,40-0,94); calidad de evidencia baja), en comparación con las mujeres que recibieron 17-OHPC. No hubo diferencias significativas en las tasas de PPTE < 37 semanas, < 28 semanas y < 24 semanas. La tasa de mujeres que reportaron reacciones adversas a los medicamentos fue significativamente menor en el grupo de progesterona vaginal en comparación con el grupo de 17-OHPC (7,1% vs. 13,2%; RR 0,53 (IC 95%, 0,31-0,91); calidad de la evidencia muy baja). En cuanto a los resultados neonatales, la progesterona vaginal se asoció a una menor tasa de admisiones en la unidad neonatal de cuidados intensivos en comparación con la 17-OHPC (18,7% vs. 23,5%; RR 0,63 (IC 95%, 0,47-0,83); calidad de evidencia baja). Para la comparación del 17-OHPC con la progesterona vaginal se rebajó la calidad de las pruebas para todos los resultados en al menos un grado debido a imprecisiones (no se alcanzó el tamaño óptimo de la información) y en al menos un grado debido al carácter indirecto de los estudios (diferentes intervenciones).
UNASSIGNED: La progesterona vaginal administrada diariamente (ya fuera como supositorio o como gel) desde la semana 16 de gestación es una alternativa razonable, si no mejor, a una inyección semanal de 17-OHPC para la prevención de PPTE en mujeres con embarazos de feto único e historial de PPTE. Sin embargo, el nivel de calidad de las estimaciones del resumen fue bajo o muy bajo según lo evaluado por GRADE, lo que indica que el verdadero efecto puede ser, o es probable que sea, sustancialmente diferente de la estimación del efecto. 17Α-:META: : (randomized controlled trials,RCTs)(spontaneous preterm birth,SPTB)17α-(intramuscular 17α-hydroxyprogesterone caproate,17-OHPC)SPTB。metaSPTB17-OHPCSPTB。 : ,SPTBRCTs,RCTs()17-OHPC()。。34SPTB。37、32、2824SPTB,。(relative risk,RR)95%CI。。 : 3RCTs(680)。16。,36。,90 mg,100 mg,200 mg。,RCTs250 mg 17-OHPC。17-OHPC,34 [17.5%25.0%;RR,0.71(95% CI,0.53 ~ 0.95);]32[8.9%14.5%;RR,0.62(95% CI,0.40 ~ 0.94);]SPTB。37、2824SPTB。17-OHPC,[7.1%13.2%;RR,0.53(95% CI,0.31 ~ 0.91);]。,17-OHPC,[18.7%23.5%;RR,0.63(95% CI,0.47 ~ 0.83);]。17-OHPC,(),()。 : SPTBSPTB,16()17-OHPC,。,GRADE,,。.

OBJECTIVE: With current diagnostic resources, it is impossible to predict if a patient consulting in the obstetrics emergencies with symptoms of preterm labor, preterm delivery or not. A novel test for the detection of time to spontaneous preterm delivery was developed and would predict imminent delivery in 7 or 14 days from the time of testing. The diagnostic performances of detection test of PAMG-1 have been validated before digital examination. However digital examination is usually made in first line. The objective of this study was to assess the reproducibility of these diagnostic performances after digital examination and transvaginal ultrasound cervical length.
METHODS: A prospective and observational study was conducted in a level 3 maternity (University Hospital of Saint-Etienne), from June 2013 to January 2014. Patients consulted in the obstetrics emergencies for threatened preterm birth between 24-34 weeks were enrolled with written and signed consent. Reproducibility of this test was assessed after digital examination, transvaginal ultrasound cervical length and a long time after all investigations.
RESULTS: Forty-one patients were included in our study. Average gestational age was 29 weeks, digital examination was changed in 36 patients, whereas cervical length was less than 26mm for only 17 patients. In our study, 100% of tests results remain negative or positive after digital examination and 95,1% after transvaginal ultrasound. Our results confirmed this excellent specificity (97.5% [IC 95%; 86.8-99.9]) and negative predictive value (97.5% [IC 95%; 86.8-99.9]).
CONCLUSIONS: This work allowed to demonstrate the reproducibility of detection test of PAMG-1 after a digital examination. An initial management with detection test of PAMG-1 could allow reducing the rate of unnecessary hospitalization.

Recent discoveries suggest that T-regulatory lymphocytes (Treg) might play an important role in the pathophysiology of preterm labor. The aim of this study was to assess the relationship among the levels of maternal circulating Treg cells, uterine cervical length, and the risk of preterm labor. Sixty women with regular contractions and/or cervical incompetence at 24-32 weeks\' gestation were recruited into a prospective study. Each patient underwent transvaginal ultrasound examination of the cervical length, and regulatory T cells were quantified in peripheral blood samples by flow cytometry. Patients with cervical incompetence were prescribed vaginal progesterone until birth. Measurements of Treg levels and cervical length correlated with the timing of labor. The risk of preterm labor happening within 48 h of testing was demonstrated to be almost 35 times higher (OR=35.21, CI 13.3; 214, p<0.001) in the group with simultaneously low Treg values (<0.031 × 10(9)/L) and a shortened uterine cervix (<17.5mm), compared with the situation where both of these values were normal. Similar results were found in predicting preterm delivery before 34 weeks, or between 34 and 37 weeks. A statistically nonsignificant trend toward increased cervical length and increased Treg count was noted in the women on progesterone treatment. We show for the first time that the combined assessment of Treg cell count and cervical length is a much better predictor of preterm delivery than either parameter used on its own. This combined approach may offer clinical application in patients who present with risk factors for preterm labor.