Vaginal progesterone vs cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis

Conde-Agudelo, Agustín; Romero, Roberto; Nicolaides, Kypros H.; Chaiworapongsa, Tinnakorn; O’Brien, John; Çetingöz, Elçin; Fonseca, Eduardo Borges da; Creasy, George W.; Soma-Pillay, Priya; Fusey, Shalini; Çam, Çetin; Alfirević, Z̄arko; Hassan, Sonia S.

doi:10.1016/j.ajog.2012.10.877

Cited by 138 publications

(105 citation statements)

References 221 publications

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“…There are relatively few mouse models that have demonstrated a preterm birth phenotype, and these mouse models include the following: lipopolysaccharide inflammatory response (83), acute alcohol exposure in late pregnancy (84), progesterone-receptor antagonism (85), Stat5b knockout mice (86,87), inactivation of cannabinoid receptor CB1 (88), and Trp53 deletion in progesterone receptor expressing cell linages (89). A unique distinction of our model is that the gestation length was rescued by exogenous progesterone administration, the only proven clinical treatment for women with a history of preterm birth (90)(91)(92). Progesterone production in humans is different in that the syncytiotrophoblast of the placenta is the progesterone producing cells after the first 8 wk of gestation (93).…”

Section: Discussionmentioning

confidence: 99%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40-75% of human breast, ovarian, and prostate cancers. Because Becn1 is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becn1 provides essential functions in the ovary that are essential for mammalian reproduction.A utophagy is an evolutionarily conserved cellular process from yeast to mammals that recycles long-lived proteins and organelles to maintain cell energy homeostasis, and is classically activated through the nutrient sensor, mammalian target of rapamycin complex (1-3). Cellular material is encapsulated within a double phospholipid bilayer organelle called the "autophagosome," which fuses with a lysosome to degrade the internalized debris. Using genetic screens in yeast, more than 34 autophagyrelated (Atg) genes have been identified, with most having clear homologs in higher eukaryotes through protein-sequence identity (4-6). BECLIN1 (BECN1), a haploinsufficient tumor suppressor, is an essential autophagy protein that directs the initiation phase and maturation-fusion phase through its participation in two distinct phosphoinositide 3-kinase class III complexes (7-9). Autophagy is not only important for normal development, but it is linked to an array of diseases including neurodegenerative disorders, liver disease, heart disease, inflammatory diseases, and cancer (10, 11). We previously showed a role for BECN1 and autophagy in the establishment of the murine primordial follicle pools in a germ-line knockout model (12). In this study, we follow up on these results and investigate the role of BECN1 in ovarian granulosa cells.In mammals, the success of early pregnancy from embryo implantation to development of the conceptus depends on the function of an ephemeral endocrine gland, the "corpus luteum" (CL), which rapidly forms in the ovary from the remains of the ovulated follicle and migrating somatic cells through a process called "luteinization." Progesterone is an essential hormone that acts at several different levels during pregnancy, including the development of the endometrium for implantation of the embryo and the maintenance of pregnancy through quiescence of the myometrium (13,14). Luteal cells within the CL use cholesterol for steroidogenesis to produce progesterone ...

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Section: Discussionmentioning

confidence: 99%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…One review did an indirect comparison meta-analysis of vaginal progesterone and cerclage, 65 but did not combine the direct and indirect estimates or assess the probability of each intervention being the best. Our findings of reductions in PTB < 34 and <37 weeks and NND with progesterone are consistent with the previous individual systematic review on progesterone, although our findings on cerclage, with the inclusion of additional studies, differed from the previous meta-analysis, which included unpublished data 4 and in which a significant effect of cerclage in preventing PTB < 34, <37 and <28 weeks was found.…”

Section: Interpretation In Light Of Other Evidencementioning

confidence: 99%

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta‐analysis

Jarde

Lutsiv

Park

et al. 2017

BJOG

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Background Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it.Objectives To compare progesterone, cerclage and pessary, determine their relative effects and rank them.Search strategy We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews.Selection criteria We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study.Data collection and analysis We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT).Main results We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks.Conclusions Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae.Keywords Cervical cerclage, cervical pessary, network metaanalysis, preterm birth, progesterone, systematic review.Tweetable abstract Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.Please cite this paper as: Jarde A, Lutsiv O, Park CK, Beyene J, Dodd JM, Barrett J, Shah PS, Cook JL, Saito S, Biringer AB, Sabatino L, Giglia L, Han Z, Staub K, Mundle W, Chamberlain J, McDonald SD. Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

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“…Both interventions were associated with a statistically significant reduction in the risk of preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in reducing preterm birth or adverse perinatal outcomes 41 .…”

Section: Discussion:-mentioning

confidence: 99%

Pregnancy Outcome in Short Cervix: Progesterone vs Cervical Encerclage.

Gandotra¹,

Nimbargi²

2017

IJAR

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Vaginal progesterone vs cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis

Cited by 138 publications

References 221 publications

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta‐analysis

Pregnancy Outcome in Short Cervix: Progesterone vs Cervical Encerclage.

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