Progesterone to prevent preterm birth in twin gestations: what is the next step forward?

Progesterone is a key hormone for pregnancy maintenance, and a decline in progesterone action is considered to be central to the initiation of parturition in most mammalian species, including primates.1, 2 This hormone acts in all components of the common pathway of parturition1-3 and promotes myometrial quiescence, inhibits cervical ripening, and down-regulates the production of chemokines [such as interleukin (IL)-8] by the chorioamniotic membranes.4 Importantly, the administration of progesterone receptor antagonists [i.e. mifepristone (RU486) or onapristone (ZK98299)] to pregnant women, non-human primates and guinea pigs can induce the onset of labor and cervical ripening.5 Thus, it is not surprising that many investigators have explored the use of progesterone for the prevention of preterm birth.

[1]  V. Serra,et al.  Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial , 2013, BJOG : an international journal of obstetrics and gynaecology.

[2]  R. Brant,et al.  Vaginal progesterone to prevent preterm birth in multiple pregnancy: a randomized controlled trial , 2012, Journal of perinatal medicine.

[3]  K. Nicolaides,et al.  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. , 2012, American journal of obstetrics and gynecology.

[4]  N. Uldbjerg,et al.  OC01.01: Prevention of preterm delivery in twin gestations (PREDICT): a multicentre randomised placebo‐controlled trial on the effect of vaginal micronised progesterone , 2011 .

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[6]  L. Sullivan,et al.  Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double‐blind, placebo‐controlled trial , 2011, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

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[9]  T. Garite,et al.  Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial. , 2010, American journal of obstetrics and gynecology.

[10]  R. Romero,et al.  Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis. , 2010, American journal of obstetrics and gynecology.

[11]  R. Romero,et al.  434: The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes , 2009 .

[12]  Steven Thornton,et al.  Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis , 2009, The Lancet.

[13]  J. Thorp,et al.  Prevention of Preterm Birth in Triplets Using 17 Alpha-Hydroxyprogesterone Caproate: A Randomized Controlled Trial , 2009, Obstetrics and gynecology.

[14]  R. Romero.  Prenatal medicine: The child is the father of the man* , 2009, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[15]  R. Romero,et al.  Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions. , 2008, American journal of obstetrics and gynecology.

[16]  Roberto Romero,et al.  Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment , 2007, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[17]  J. Weeks,et al.  Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double‐blind, placebo‐controlled trial , 2007, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[18]  J. Weeks,et al.  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 , 2007, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[19]  Elizabeth A Thom,et al.  A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. , 2007, The New England journal of medicine.

[20]  K. Nicolaides,et al.  Progesterone and the risk of preterm birth among women with a short cervix. , 2007, The New England journal of medicine.

[21]  R. Romero,et al.  The preterm parturition syndrome , 2006, BJOG : an international journal of obstetrics and gynaecology.

[22]  Gerard Tromp,et al.  The use of high‐dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome , 2006, BJOG : an international journal of obstetrics and gynaecology.

[23]  P. Bennett,et al.  Progesterone Represses Interleukin-8 and Cyclo-Oxygenase-2 in Human Lower Segment Fibroblast Cells and Amnion Epithelial Cells1 , 2003, Biology of reproduction.

[24]  S. Thornton,et al.  The involvement of progesterone in the onset of human labour. , 2003, European journal of obstetrics, gynecology, and reproductive biology.

[25]  M. Zugaib,et al.  Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. , 2003, American journal of obstetrics and gynecology.

[26]  H. Wolfe,et al.  Patients with an ultrasonographic cervical length < or =15 mm have nearly a 50% risk of early spontaneous preterm delivery. , 2000, American journal of obstetrics and gynecology.

[27]  K. Nicolaides,et al.  Cervical Length at 23 Weeks in Twins in Predicting Spontaneous Preterm Delivery , 1999, Obstetrics and gynecology.

[28]  J. Hobbins,et al.  Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor. , 1990, American journal of obstetrics and gynecology.

[29]  W. Grobman.  838: Randomized controlled trial of progesterone treatment for preterm birth prevention in nulliparous women with cervical length less than 30 mm , 2012 .