- Using the vaginal progesterone in prophylaxis of preterm birth: if there are benefits?
Using the vaginal progesterone in prophylaxis of preterm birth: if there are benefits?
HEALTH OF WOMAN. 2016.4(110):28–36; doi 10.15574/HW.2016.110.28
Using the vaginal progesterone in prophylaxis of preterm birth: if there are benefits?
Mogilevkina I., Gurianov V.
National Medical Academy of Postgraduate Education P. L. Shupyk, Kiev
A.A. Bogomolets National Medical University, Kiev
The objective: to conduct data and conclusions analysis provided by the investigators of OPPTIMUM Study in terms of compliance to ethical principles and principles of biostatistics.
Patients and methods. Рublished data by NormanJ. et al., Vaginal progesterone prophylaxis for preterm birth (OPPTIMUM): a multicenter, randomized, double-blind trial//Lancet. 2016; on-line calculator: https://www.sealedenvelope.com/power/binary-superiority; Gpower and MedCalc v.16.4.1. software.
Results. OPPTIMUM study has several problems which make the research outcomes and conclusions questionable. Usage of placebo during recent 2 years of the study in women with a cervix length Ј 25 mm (since the National protocols for medical care in this particular case has been changed) provokes an ethical question. From biostatistics point of view the study is associated with a low compliance (69%), which led to insufficient statistical power for evaluating obstetrics outcomes and effects of vaginal micronized progesterone in women with a short cervix.
Conclusion. The results of OPPTIMUM Study do not allow to make a conclusion that the efficacy of vaginal progesterone in improving outcomes in prevention of preterm birth in women with a singleton pregnancy and a short cervix is either non-existent or weak. FIGO recommendations from 2015 for usage of vaginal micronized progesterone for prophylaxis of preterm birth in women with a short cervix remain to be relevant because of no evidence to change them.
Key words: preterm birth, vaginal micronized progesterone.
1. Behrman RE, Butler AS, editors. 2007. Preterm Birth: Causes, Consequences, and Prevention. Institute of Medicine of the National Academies. The National Academies Press. Washington D.C.:772.
2. Ananth CV, Joseph KS, Oyelese Y et al. 2005. Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000. Obstet. Gynecol. 105:1084–1091. http://dx.doi.org/10.1097/01.AOG.0000158124.96300.c7; PMid:15863548
3. Jackson RA, Gibson KA, Wu YW, Croughan MS. 2004. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet. Gynecol. 103:551–563. http://dx.doi.org/10.1097/01.AOG.0000114989.84822.51; PMid:14990421
4. Goldenberg RL, Iams JD, Mercer BM et al. 1998. The preterm prediction study: the value of new vs. standard risk factors in predicting early and all spontaneous preterm births. Am. J. Public. Health. 88:233–238. http://dx.doi.org/10.2105/AJPH.88.2.233; PMid:9491013 PMCid:PMC1508185
5. Romero R, Espinosa J, Kusanovic JP et al. 2006. The preterm parturition syndrome. Br. J. Obstet. Gynecol. 113:17-42. http://dx.doi.org/10.1111/j.1471-0528.2006.01120.x; PMid:17206962
6. Romero R, Espinoza J, Mazor M, Chaiwarapongsa T. 2004. The preterm parturition syndrom. Preterm Birth /Eds. H. Critchely, P. Bennett, S. Thortnton S. London: RCOG Press:28–60.
7. Goldenberg RL, Culhane JF, Iams JD, Romero R. 2008. Epidemiology and causes of preterm birth. Lancet. 371:75–84. http://dx.doi.org/10.1016/S0140-6736(08)60074-4
8. Campbel S. 2011. Universal cervical-length screening and vaginal progesterone prevents early preterm birth, reduces neonatal morbidity and is cost saving: doing nothing is no longer an option. Ultrasound Obstet. Gynecol. 38:1–9. http://dx.doi.org/10.1002/uog.9073; PMid:21713990
9. Celik E, To M, Gajewska K et al. 2011. Cervical length and obstetric history predict spontaneous preterm birth: development and validation of a model to provide individualized risk assessment. Ultrasound Obstet. Gynecol. 31:549–554. http://dx.doi.org/10.1002/uog.5333; PMid:18432605
10. Fronseca E, Celik E, Parra M et al. 2007. Progesterone and the risk of preterm birth among women with a short cervix. New Engl. J. Med. 357:462–469. http://dx.doi.org/10.1056/NEJMoa067815; PMid:17671254
11. Best practice in maternal-fetal medicine. FIGO Working Group On Best Practice In Maternal-Fetal Medicine. Int. J. Gynaecol. Obstet. 2015. 128:80–82. http://dx.doi.org/10.1016/j.ijgo.2014.10.011; PMid:25481030
12. Norman JE, Marlow N, Messow CM et al. 2016, February 23. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomized, double-blind trial. Lancet. Published online.
13. Fetal fibronectin testing for reducing the risk of preterm birth. The WHO Reproductive Health Library summary. 2015, April.
14. Goldenberg R et al. 1998. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. American Journal of Public Health 88:233–238. http://dx.doi.org/10.2105/AJPH.88.2.233; PMid:9491013 PMCid:PMC1508185
15. Heath V et al. 2000. Cervicovaginal fibronectin and cervical length at 23 weeks of gestation: relative risk of early preterm delivery. British Journal of Obstetrics and Gynaecology 107:1276–1281. http://dx.doi.org/10.1111/j.1471-0528.2000.tb11620.x; PMid:11028581
16. Kiefer D, Vintzileos A. 2008. The Utility of Fetal Fibronectin in the Prediction and Prevention of Spontaneous Preterm Birth. Reviews in Obstetrics & Gynecology 1(3):106–112. PMid:19015761 PMCid:PMC2582650
17. Royal College of Obstetricians and Gynaecologists (RCOG). Cervical cerclage. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2011 May. (Green-top guideline; no. 60): 21.
18. Kurtzman J, Chandiramani M, Briley A, Poston L, Das A, Shennan A. 2009. Quantitative fetal fibronectin screening in asymptomatic high-risk patients and the spectrum of risk for recurrent preterm delivery. American Journal of Obstetrics & Gynecology. 200(3):263. e1-6.
19. Peaceman AM, Andrews WW, Thorp JM et al. 1997. Fetal fibronectin as a predictor of preterm birth in patients with symptoms: a multicenter trial. Am J Obstet. Gynecol. 177:13–18. PubMed. http://dx.doi.org/10.1016/S0002-9378(97)70431-9
20. Heath V et al. Cervicovaginal fibronectin and cervical length at 23 weeks of gestation: relative risk of early preterm delivery. An International Journal of Obstet. And Gynecology 107(10):1276–1281.
21. Fernandes MS, Pierron V, Michailovich D et al. 2005. Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J. Endocr. 187:89–101. http://dx.doi.org/10.1677/joe.1.06242; PMid:16214944
22. Karteris E, Zervou S, Pang Y et al. 2006. Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term. Molec. Endocr. 20:1519–1534. http://dx.doi.org/10.1210/me.2005-0243; PMid:16484338
23. Marx SG, Wentz MJ, Mackay LB et al. 2006. Effects of progesterone on iNOS, COX-2 and collagen expression in the cervix. J. Histochem. Cytochem. 54:623–639. http://dx.doi.org/10.1369/jhc.5A6759.2006; PMid:16399999
24. Romero R, Nicolaides K, Conde-Agudelo A et al. 2012. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Amer. J. Obstet. Gynecol. 2026:124. e-19.
25. Fronseca E, Celik E, Parra M et al. 2007. Progesterone and the risk of preterm birth among women with a short cervix. New Engl. J. Med. 357:462–469. http://dx.doi.org/10.1056/NEJMoa067815; PMid:17671254
26. Hassan SS, Romero R, Vidyadhari D et al. 2011. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, placebo-controlled trial. Ultrasound Obstet. Gynec. 38:18–31. http://dx.doi.org/10.1002/uog.9017; PMid:21472815 PMCid:PMC3482512
27. Cetingoz E, Cam C, Sakali M et al. 2011. Progesterone effect on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial. Arch. Gynecol. Obstet. 283:423–429. http://dx.doi.org/10.1007/s00404-009-1351-2; PMid:20091317
28. DeFranco EA, O’Brien JM, Adair CD et al. 2007. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 30:697–705. http://dx.doi.org/10.1002/uog.5159; PMid:1789957
29. Rode L, Kein K, Nicolaides K et al. 2011. Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet. Gynec. 38:272–280. http://dx.doi.org/10.1002/uog.9093; PMid:21739497