Abstract
Purpose
The purpose of this study was to evaluate whether the prophylactic administration of vaginal progesterone would reduce the preterm birth rate in high-risk population including singleton and twin pregnancies.
Methods
This was a randomized, double blind, placebo-controlled study that included 150 high-risk pregnancies. Risk groups included prior spontaneous preterm birth, twin pregnancy, and uterine malformation. Micronized progesterone or placebo (100 mg) was administered daily by vaginal suppository between 24 and 34 weeks of gestation. We compared progesterone and placebo groups for incidence of preterm labor and preterm delivery. Data were compared by χ² analysis and Fisher exact test.
Results
There was a statistically significant difference in the rate of preterm labor between placebo and progesterone groups (45.7 vs. 25%, respectively; p < 0.05). More women delivered before 37 weeks in placebo group (57.2%) than in progesterone group (40%; p < 0.05). Administering progesterone also reduced the preterm birth before 34 weeks of gestation. The difference between placebo and progesterone group was statistically significant (24.3 vs. 8.8%; p < 0.05). However, there was no significant difference in neonatal death between placebo and progesterone groups.
Conclusion
Prophylactic vaginal progesterone reduced the rate of preterm labor and preterm delivery in high-risk pregnancies.
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References
National Center for Health Statics (NVSR) (2001) Deaths and percentage of total deaths for the 10 leading causes of neonatal and postnatal deaths: United States. Accessed February 7, 2005
Rush RW, Davey DA, Segall ML (1978) The effect of preterm delivery on perinatal mortality. Br J Obstet Gynecol 85:806–811
Gluckman PD, Hanson MA (2004) Living with the past: evolution, development and patterns of disease. Science 305:1733–1736
Rebar RW, Cedars MI (1992) Hypergonadotropic forms of amenorrhea in young women. Endocrinol Metab Clin North Am 21:173–191
Stites DP, Siiteri PK (1983) Steroids as immunosuppressants in pregnancy. Immunol Rev 75:117–138
Siiteri PK,Seron-Ferre M (1981) Some new thoughts on the feto-placental unit and parturition in primates. In: Novy MJ, Reskko JA (eds) Fetal endocrinology. Academic Press, New York, pp 1–34
Keirse MJN (1990) Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol 97:149–154
Goldstein P, Berrier J, Rosen S, Sacks HS, Chalmers TC (1989) A meta-analysis of randomised control trials of progestational agents in pregnancy. Br J Obstet Gynecol 96:265–274
Daya S (1989) Efficacy of progesterone support for pregnancy in women with recurrent miscarriage: a meta-analysis of controlled trials. Br J Obstet Gynecol 96:275–280
Hartikainen-Sorri AL, Kauppila A, Tuimala R (1980) Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy. Obstet Gynecol 56:692–695
da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M (2003) Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized plasebo-controlled double-blind study. Am J Obstet Gynecol 188:419–424
Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH et al (2003) Prevention of recurrent preterm delivery by 17 alpha- hydroxyprogesterone caproate. N Engl J Med 348:2379–2385
O’Brien JM, Adair CD, Lewis DF et al (2007) Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double blind, placebo-controlled trial. Ultrasound Obstet Gynecol 30:687–696
Dodd JM, Flenady V, Cinctta R, Crowther CA (2006) Prenatal administration of progesterone for preventing preterm birth. Cochrane Database Syst Rev 25(1):CD004947
Dodd JM, Flenady V, Cinctta R, Crowther CA (2008) Progesterone for the prevention of preterm birth: a systemic review. Obstet Gynecol 112(1):127–134
American College of Obstetricians and Gynecologist (2003) Use of progesterone to reduce preterm birth: ACOG committee opinion No.2919. Obstet Gynecol 102:1115–1116
Tita AT, Rouse DJ (2009) Progesterone for preterm birth prevention: an evolving intervention. Am J Obstet Gynecol 200(3):219–224
Friedler S, Roziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R (1999) Luteal support with micronized progesterone following in vitro fertilization using a down-regulation protocol with gonodotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod 14:1944–1948
Miles RA, Paulson RJ, Lobo RA, Pres MF, Dahmoush L, Sauer MV (1994) Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril 62:485–490
Cicinelli E, de Ziegler D, Bulletti C, Matteo MG, Schonauer LM, Galantino P (2000) Direct transport of progesterone from vagina to uterus. Obstet Gynecol 95(3):403–406
Garfield RE, Dannan MS, Daniel EE (1980) Gap junction formation in myometrium: control by estrogens, progesterone and prostaglandins. Am J Physiol 238:C81–C89
Challis JRG, Lye SJ (1994) The physiology of reproduction. In: Knobil E, Neill JD (eds) Parturition. Raven Press, New York, pp 985–1031
Amon E (1999) Preterm labor. In: Reece EA, Hobbins JC (eds) Medicine of the fetus and mothers. Lippincott-Raven, Philadelphia, pp 1529–1579
Fuchs AR, Fuchs F (1984) Endocrinology of human parturition: a review. Br J Obstet Gynecol 91:948–967
Mitchell B, McLain CB, Challis J (1982) Local modulation of progesterone production in human fetal membranes. J Clin Endocrin Metab 55:1237–1239
Romero R, Scoccia B, Mazor M, Wu YK, Benveniste R (1988) Evidence for a local change in the progesterone/estogen ratio in human parturition at term. Am J Obstet Gynecol 159:657–660
Bernal AL (2007) Overview: Preterm labour: mechanisms and management. BMC Pregnancy and Childbirth 7:1471-2393-7-S1-S2
Rath W (1994) Die Übertragung der Schwagerschaft. Prostoglandine als Ursache für den Gebeeurtsbeginn. Zebeburtsh U. Perinat 198:207–214
Cunningham FG, Macdonald PC, Gant NF, Leveno KJ, Gilstrap LC (1997) Preterm and post-term pregnancy and fetal growth retardation. Williams obstetrics, 20th edn. Prentice-Hall, New Jersey, pp 797–826
Lockwood CJ, Senyei AE, Dischie MR et al (1991) Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med 325:669–674
Mazor M, Hershkovitz R, Chaim W, Levy J et al (1994) Human preterm birth is associated with systemic and local changes in progesterone/17b-estradiol ratios. Am J Obstet Gynecol 171:231–236
Sanchez-Ramos L, Kaunitz AM, Delke I (2005) Progestational agents to prevent preterm birth: a meta-analysis of randomised controlled trials. Am J Gynecol 105:273–279
Farine D, Mundle WR, Dodd J (2008) The use of progesterone for prevention of preterm birth. J Obstet Gynecol Can 30:67–71
King JF, Grant AM, Keirse MJNC, Chalmers I (1988) Beta-mimetics in preterm labour: an overview of randomized controlled trials. Br J Obstet Gynecol 95:211–222
O’Leary JA (1986) Prophylactic tocolysis of twins. Am J Obstet Gynecol 154:904–905
Allbert JR, Wise CA, Lou CH, Gookin KS, Parmenter MA, Morrison JC (1992) Subcutaneous tocolytic infusion therapy for patients at very high risk for preterm birth. J Perinatol 12:28–31
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Cetingoz, E., Cam, C., Sakallı, M. et al. Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial. Arch Gynecol Obstet 283, 423–429 (2011). https://doi.org/10.1007/s00404-009-1351-2
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DOI: https://doi.org/10.1007/s00404-009-1351-2