Cervical pessary in pregnant women with a short cervix
An Arabin® pessary is a flexible, ring-like silicone pessary, which has been suggested to reduce the preterm birth rate. One multicenter randomized control trial (RCT) assessed if the pessary conferred benefit in women with singleton pregnancies and a short cervix in comparison with progesterone, finding no decrease in preterm birth below 37 weeks’ gestation.[149]Hoffman MK, Clifton RG, Biggio JR, et al. Cervical pessary for prevention of preterm birth in individuals with a short cervix: the TOPS randomized clinical trial. JAMA. 2023 Jul 25;330(4):340-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369212
http://www.ncbi.nlm.nih.gov/pubmed/37490086?tool=bestpractice.com
A 2022 Cochrane review found that the pessary may reduce the risk of delivery before 37 weeks (risk ratio [RR] 0.68, 95% CI 0.44 to 1.05) and 34 weeks (RR 0.72, 95% CI 0.33 to 1.55) in asymptomatic high risk women with singleton pregnancies compared with no treatment.[150]Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA, et al. Cervical pessary for preventing preterm birth in singleton pregnancies. Cochrane Database Syst Rev. 2022 Dec 1;12(12):CD014508.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014508/full
http://www.ncbi.nlm.nih.gov/pubmed/36453699?tool=bestpractice.com
However, the evidence was low- to moderate-certainty and should be interpreted with caution due to statistical heterogeneity, imprecision, and risk of bias. Efficacy compared with progesterone was also uncertain, and there was little effect from the pessary with regards to maternal infection, neonatal unit admission, or neonatal mortality.[150]Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA, et al. Cervical pessary for preventing preterm birth in singleton pregnancies. Cochrane Database Syst Rev. 2022 Dec 1;12(12):CD014508.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014508/full
http://www.ncbi.nlm.nih.gov/pubmed/36453699?tool=bestpractice.com
Studies found no benefit from the pessary for reducing preterm delivery rates in unselected twin pregnancies and in higher risk twin pregnancies with short cervix.[151]Norman JE, Norrie J, MacLennan G, et al. Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): an open-label randomised trial and updated meta-analysis. PLoS Med. 2021 Mar;18(3):e1003506.
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003506
http://www.ncbi.nlm.nih.gov/pubmed/33780463?tool=bestpractice.com
[152]D'Antonio F, Berghella V, Di Mascio D, et al. Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: a systematic review and network meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2021 Jun;261:166-77.
http://www.ncbi.nlm.nih.gov/pubmed/33946019?tool=bestpractice.com
Progesterone therapies
Progesterone therapies reduce the incidence of preterm birth in women who have had a previous spontaneous preterm birth and in women who were incidentally found to have a short cervix.[84]EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021 Mar 27;397(10280):1183-94.
https://eprints.whiterose.ac.uk/177300
http://www.ncbi.nlm.nih.gov/pubmed/33773630?tool=bestpractice.com
In the US, the Food and Drug Administration (FDA) has withdrawn its approval for intramuscular hydroxyprogesterone as large commercial studies have not confirmed benefit. However, one meta-analysis suggests both vaginal and intramuscular preparations of progesterone may be beneficial in singleton pregnancies, with both reducing preterm delivery before 34 weeks gestation in high-risk singleton pregnancies (RR 0.78, 95% CI 0.68 to 0.90 and RR 0.83, 95% CI 0.68 to 1.01 respectively).[84]EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021 Mar 27;397(10280):1183-94.
https://eprints.whiterose.ac.uk/177300
http://www.ncbi.nlm.nih.gov/pubmed/33773630?tool=bestpractice.com
Although this meta-analysis did include women without a short cervix or other risk factors for preterm delivery, the numbers were small, and hence evidence is lacking to routinely offer women with no risk factors prophylactic progesterone. Evidence to support the use of oral preparations is lacking.[84]EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021 Mar 27;397(10280):1183-94.
https://eprints.whiterose.ac.uk/177300
http://www.ncbi.nlm.nih.gov/pubmed/33773630?tool=bestpractice.com
In multiple pregnancies, progesterone was not beneficial and may increase adverse effects.[84]EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021 Mar 27;397(10280):1183-94.
https://eprints.whiterose.ac.uk/177300
http://www.ncbi.nlm.nih.gov/pubmed/33773630?tool=bestpractice.com
[85]Sotiriadis A, Papatheodorou S, Makrydimas G. Perinatal outcome in women
treated with progesterone for the prevention of preterm birth: a meta-analysis.
Ultrasound Obstet Gynecol. 2012 Sep;40(3):257-66.
http://onlinelibrary.wiley.com/doi/10.1002/uog.11178/full
http://www.ncbi.nlm.nih.gov/pubmed/22611023?tool=bestpractice.com
[86]Dodd JM, Grivell RM, OBrien CM, et al. Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy. Cochrane Database Syst Rev. 2019 Nov 20;2019(11):CD012024.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012024.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/31745984?tool=bestpractice.com
The effect of progesterone on neonatal and maternal outcomes is less certain. Meta-analyses suggest consistently favorable neonatal outcomes but highlight the uncertainty of this effect.[70]Care A, Nevitt SJ, Medley N, et al. Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis. BMJ. 2022 Feb 15;376:e064547.
https://www.bmj.com/content/376/bmj-2021-064547.long
http://www.ncbi.nlm.nih.gov/pubmed/35168930?tool=bestpractice.com
[84]EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021 Mar 27;397(10280):1183-94.
https://eprints.whiterose.ac.uk/177300
http://www.ncbi.nlm.nih.gov/pubmed/33773630?tool=bestpractice.com
Data is limited on the long-term effects of progesterone, but one systematic review reported no effects on children ages up to 8 years exposed to progesterone in utero, and a 4 year follow-up study showed no differences between 17-hydroxyprogesterone and placebo in any developmental outcomes assessed.[153]Northern AT, Norman GS, Anderson K, et al. Follow up of children exposed in utero to 17-alpha hydroxyprogesterone caproate compared with placebo. Obstet Gynecol. 2007 Oct;110(4):865-72.
http://www.ncbi.nlm.nih.gov/pubmed/17906021?tool=bestpractice.com
[154]Simons NE, Leeuw M, Van't Hooft J, et al. The long-term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review. BJOG. 2021 May;128(6):964-74.
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.16582
http://www.ncbi.nlm.nih.gov/pubmed/33112462?tool=bestpractice.com