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Progestogens in Threatened Miscarriage

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Progestogens in Obstetrics and Gynecology

Abstract

Threatened miscarriage (bleeding during the first 20 weeks of pregnancy) may progress to miscarriage or may resolve. Progestational agents have been prescribed since the 1950s in order to prevent threatened miscarriage progressing to miscarriage. There is much theoretical data to support the use of progestogens. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Therefore, the question arises whether progestogens should be used in threatened miscarriage.

A recent Cochrane review found progestogens to be effective for the treatment of threatened miscarriage with no harmful effects on mother or fetus. Two trials of dydrogesterone and two trials of vaginal progesterone were compared to placebo. The overall results showed a statistically significant result in favour of progestogens. The results were not statistically different for vaginal progesterone (RR = 0.47 95 % CI, 0.17–1.30), whereas dydrogesterone was effective (RR = 0.54 CI 0.35–0.84). Based on these results, both the U.K. National Institute of Health and Care excellence (NICE) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) have claimed that progestogens improve the prognosis, but indicated the need for further trials. The author tried to expand the figures in the Cochrane review by including less robust trials in an expanded analysis. At that time there were no further trials available on vaginal progesterone although one further trial of vaginal micronised progesterone has since been published. Three additional randomised trials were identified comparing dydrogesterone to standard management in threatened miscarriage. 660 patients were eligible for analyses. There was a 47 % reduction in the miscarriage rate (OR = 0.47 CI 0.31–0.7), there was a 13 % (44/335) miscarriage rate after dydrogesterone administration compared to 24 % in control women.

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References

  1. Farrell T, Owen P. The significance of extra chorionic membrane separation in threatened miscarriage. BJOG. 1996;103:926–8.

    Article  CAS  Google Scholar 

  2. Everett C. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. BMJ. 1997;315:32–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Szekeres-Bartho J, Barakonyi A, Par G, Poigar B, Palkovics T, Szereday L. Progesterone as an immunomodulatory molecule. Int Immunopharmacol. 2001;1:1037–48.

    Article  CAS  PubMed  Google Scholar 

  4. Stovall TG, Ling FW, Andersen RN, Buster JE. Improved sensitivity and specificity of a single measurement of serum progesterone over serial quantitative beta-human chorionic gonadotrophin in screening for ectopic pregnancy. Hum Reprod. 1992;7:723–5.

    CAS  PubMed  Google Scholar 

  5. al-Sebai MA, Kingsland CR, Diver M, Hipkin L, McFadyen IR. The role of a single progesterone measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability. Br J Obstet Gynaecol. 1995;102:364–9.

    Article  CAS  PubMed  Google Scholar 

  6. Csapo AI, Pulkkinen MO. Indispensability of the human corpus luteum in the maintenance of early pregnancy: lutectomy evidence. Obstet Gynecol Surv. 1978;3:69–81.

    Article  Google Scholar 

  7. Weiss JL, Malone FD, Vidaver J, Ball RH, Nyberg DA, Comstock CH, et al. Threatened abortion: a risk factor for poor pregnancy outcome, a population-based screening study. Am J Obstet Gynecol. 2004;190:745–50.

    Article  PubMed  Google Scholar 

  8. Reginald PW, Beard RW, Chapple J, Forbes PB, Liddell HS, Mowbray JF, Underwood JL. Outcome of pregnancies progressing beyond 28 weeks gestation in women with a history of recurrent miscarriage. Brit J Obstet Gynaecol. 1987;94:643–8.

    Article  CAS  Google Scholar 

  9. Carp HJA, Toder V, Mashiach S, et al. Recurrent miscarriage: a review of current concepts, immune mechanisms, and results of treatment. Obst Gynecol Surv. 1990;45:657–69.

    Article  CAS  Google Scholar 

  10. Li TC, Makris M, Tomsu M, Tuckerman E, Laird S. Recurrent miscarriage: aetiology, management and prognosis. Hum Reprod Update. 2002;8:463–81.

    Article  CAS  PubMed  Google Scholar 

  11. Laufer MR, Ecker JL, Hill JA. Pregnancy outcome following ultrasound-detected fetal cardiac activity in women with a history of multiple spontaneous abortions. J Soc Gynecol Investig. 1994;1(2):138–42.

    CAS  PubMed  Google Scholar 

  12. Stovall TG, Ling FW, Carson SA, Buster JE. Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. Fertil Steril. 1992;57:456–7.

    CAS  PubMed  Google Scholar 

  13. Arck PC, Rücke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, et al. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reprod Biomed Online. 2008;17(1):101–13.

    Article  PubMed  Google Scholar 

  14. Tuckerman E, Laird SM, Stewart R, Wells M, Li TC. Markers of endometrial function in women with unexplained recurrent pregnancy loss. Hum Reprod. 2004;19:196–205.

    CAS  PubMed  Google Scholar 

  15. Abraham GE, Maroulis GB, Marshall JR. Evaluation of ovulation and corpus luteum function using measurements of plasma progesterone. Obstet Gynecol. 1974;44:522–5.

    CAS  PubMed  Google Scholar 

  16. Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod. 2003;18:1724–32.

    Article  CAS  PubMed  Google Scholar 

  17. Boue J, Boue A, Lazar P. The epidemiology of human spontaneous abortions with chromosomal anomalies. In: Blandau RJ, editor. Aging gametes. Karger & Co: Basel; 1975. p. 330.

    Google Scholar 

  18. Sanchez JM, Franzi L, Collia F, De Diaz SL, Panal M, Dubner M. Cytogenetic study of spontaneous abortions by transabdominal villus sampling and direct analysis of villi. Prenat Diag. 1999;19:601–3.

    Article  CAS  Google Scholar 

  19. Stein Z. Early fetal loss. Birth Def. 1981;17:95–9.

    CAS  Google Scholar 

  20. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Rajcan-Separovic E, Diego-Alvarez D, Robinson WP, Tyson C, Qiao Y, Harvard C, Fawcett C, Kalousek D, Philipp T, Somerville MJ, Stephenson MD. Identification of copy number variants in miscarriages from couples with idiopathic recurrent pregnancy loss. Hum Reprod. 2010;25:2913–22.

    Article  CAS  PubMed  Google Scholar 

  22. Wahabi HA, Fayed AA, Esmaeil SA, Al Zeidan RA. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev 2011;(12):CD005943.

    Google Scholar 

  23. El-Zibdeh MY, Yousef LT. Dydrogesterone support in threatened miscarriage. Maturitas. 2009;65 Suppl 1:S43–6.

    Article  CAS  PubMed  Google Scholar 

  24. Pandian RU. Dydrogesterone in threatened miscarriage: a Malaysian experience. Maturitas. 2009;65 Suppl 1:S47–50.

    Article  CAS  PubMed  Google Scholar 

  25. Gerhard I, Gwinner B, Eggert-Kruse W, Runnebaum B. Double-blind controlled trial of progesterone substitution in threatened abortion. Biol Res Pregnancy Perinatol. 1987;8:26–34.

    CAS  PubMed  Google Scholar 

  26. Palagiano A, Bulletti C, Pace MC, De Ziegler D, Cicinelli E, Izzo A. Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy. Ann N Y Acad Sci. 2004;1034:200–10.

    Article  CAS  PubMed  Google Scholar 

  27. National Institute for Health and Care Excellence. Nice clinical Guideline No. 154, Ectopic pregnancy and miscarriage. 2012; http://www.nice.org.uk/guidance/cg154

  28. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Progesterone support of the luteal phase and in the first trimester. 2013; www.ranzcog.edu.au

  29. Ehrenskjöld ML, Bondo B, Weile F. Treatment of threatened abortion with dydrogesterone. Ugeskr Laeger. 1967;129:1678–9 [Article in Danish].

    PubMed  Google Scholar 

  30. Mistò A. Experiences with 6-dehydro-retroprogesterone int the treatment of placental insufficiency. Ann Ostet Ginecol Med Perinat. 1967;89:102–12 [Article in Italian].

    PubMed  Google Scholar 

  31. Omar MH, Mashita MK, Lim PS, Jamil MA. Dydrogesterone in threatened abortion: pregnancy outcome. J Steroid Biochem Mol Biol. 2005;97:421–5.

    Article  CAS  PubMed  Google Scholar 

  32. Carp H. A systematic review of dydrogesterone for the treatment of threatened miscarriage. Gynecol Endocrinol. 2012;28:983–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Yassaee F, Shekarriz-Foumani R, Afsari S, Fallahian M.The effect of progesterone suppositories on threatened abortion: a randomized clinical trial. J Reprod Infertil. 2014; 15:147–51.

    PubMed Central  PubMed  Google Scholar 

  34. Chernyshov VP, Vodyanik MA, Pisareva SP. Lack of soluble TNF-receptors in women with recurrent spontaneous abortion and possibility for its correction. Am J Reprod Immunol. 2005;54:284–91.

    Article  CAS  PubMed  Google Scholar 

  35. Shearman RP, Garrett WJ. Double-blind study of effect of 17- hydroxyprogesterone caproate on abortion rate. Br Med J. 1963;1(5326):292–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Ruddok NK, Shi SQ, Jain S, Moore G, Hankins GDV, Romero R, Garfield RE. Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions. Am J Obstet Gynecol. 2008;199(391):e1–7.

    Google Scholar 

  37. Sauebrei EE. Early pregnancy: pre-embryonic and embryonic periods. In: Sauebrei EE, Nguyen KT, Nolan RL, editors. A practical guide to ultrasound in obstetrics and gynecology. Philadelphia, PA: Lippincott-Raven Publishers; 1998. p. 122–31.

    Google Scholar 

  38. Bennett GL, Bromley B, Lieberman E, Benacerraf BR. Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography. Radiology. 1996;200(3):803–6.

    Article  CAS  PubMed  Google Scholar 

  39. Tuuli MG, Norman SM, Odibo AO, Macones GA, Cahill AG. Perinatal outcomes in women with subchorionic hematoma: a systematic review and meta-analysis. Obstet Gynecol. 2011;117:1205–12.

    Article  PubMed  Google Scholar 

  40. Pelinescu-Onciul D, Radulescu-Botica R, Steriu M, Cheles C, Varlas V. Terapia cu progesteron micronizat a hematoamelor eciduale. Infomedica. 1999;2S:32–5.

    Google Scholar 

  41. Pelinescu-Onciul D. Subchorionic hemorrhage treatment with dydrogesterone. Gynecol Endocrinol. 2007;23 Suppl 1:77–81.

    Article  CAS  PubMed  Google Scholar 

  42. Kallen B, Castilla EE, Robert E, Lancaster PAL, Kringeelbach M, Mutchinick O, et al. An international case–control study on hypospadias. The problem with variability and the beauty of diversity. Eur J Epidemiol. 1992;8:256–63.

    Article  CAS  PubMed  Google Scholar 

  43. Kallen B, Martinez-Frias ML, Castilla EE, Robert E, Lancaster PAL, Kringelbach M, et al. Hormone therapy during pregnancy and isolated hypospadias: an international case–control study. Int J Risk Saf Med. 1992;3:183–98.

    CAS  PubMed  Google Scholar 

  44. Carmichael SL, Shaw GM, Laurent C, Croughan MS, Olney RS, Lammer EJ. Maternal progestin intake and risk of hypospadias. Arch Pediatr Adolesc Med. 2005;159:957–62.

    Article  PubMed  Google Scholar 

  45. Rock JA. Fetal malformations following progesterone therapy during pregnancy: a preliminary report. Fertil Steril. 1985;44:17–9.

    CAS  PubMed  Google Scholar 

  46. Check JH. The risk of fetal anomalies as a result of progesterone therapy during pregnancy. Fertil Steril. 1986;45:575–7.

    CAS  PubMed  Google Scholar 

  47. Bartholomeusz RK, Bruce NW. Effects of maternal progesterone supplementation on fetal, placental and corpus luteal weights in the rat. Biol Reprod. 1976;15:84–9.

    Article  CAS  PubMed  Google Scholar 

  48. Michaelis J, Michaelis H, Glück E, Koller S. Prospective study of suspected associations between certain drugs administered during early pregnancy and congenital malformations. Teratology. 1983;27:57–64.

    Article  CAS  PubMed  Google Scholar 

  49. Di Renzo GC, Mattei A, Gojnic M, Gerli S. Progesterone and pregnancy. Curr Opin Obstet Gynecol. 2005;17:598–600.

    Article  PubMed  Google Scholar 

  50. Brancazio LR, Murtha AP, Heine RP. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;349:1087–8.

    Article  CAS  PubMed  Google Scholar 

  51. O’Sullivan MD, Hehir MP, O’Brien YM, Morrison JJ. 17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy. Am J Obstet Gynecol. 2010;202:453.

    PubMed  Google Scholar 

  52. Yemini M, Borenstein R, Dreazen E, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151:574–7.

    Article  CAS  PubMed  Google Scholar 

  53. Meis PJ, Klebanoff M, Thom E, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379–85.

    Article  CAS  PubMed  Google Scholar 

  54. Keirse MJNC. Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol. 1990;97:149.

    Article  CAS  Google Scholar 

  55. Queisser-Luft A. Dydrogesterone use during pregnancy: overview of birth defects reported since 1977. Early Hum Dev. 1977;85:375–7.

    Article  Google Scholar 

  56. Tongsong T, Srisomboon J, Wanapirak C, Sirichotiyakul S, Pongsatha S, Polsrisuthikul T. Pregnancy outcome of threatened abortion with demonstrable fetal cardiac activity: a cohort study. J Obstet Gynaecol (Tokyo 1995). 1995;21:331–5.

    Article  CAS  Google Scholar 

  57. Tannirandorn Y, Sangsawang S, Manotaya S, Uerpairojkit B, Samritpradit P, Charoenvidhya D. Fetal loss in threatened abortion after embryonic/fetal heart activity. Int J Gynaecol Obstet. 2003;81:263–6.

    Article  CAS  PubMed  Google Scholar 

  58. Falco P, Milano V, Pilu G, David C, Grisolia G, Rizzo N, Bovicelli L. Sonography of pregnancies with first-trimester bleeding and a viable embryo: a study of prognostic indicators by logistic regression analysis. Ultrasound Obstet Gynecol. 1996;7:165–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Howard J. A. Carp M.B.B.S., F.R.C.O.G.

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Howard J. A. Carp M.B.B.S., F.R.C.O.G.

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  1. Howard J. A. Carp M.B.B.S., F.R.C.O.G.
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Correspondence to Howard J. A. Carp M.B.B.S., F.R.C.O.G. .

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  1. Tel Aviv University, Tel Aviv, Tel Aviv, Israel

    Howard J.A. Carp

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Carp, H.J.A. (2015). Progestogens in Threatened Miscarriage. In: Carp, H. (eds) Progestogens in Obstetrics and Gynecology. Springer, Cham. https://doi.org/10.1007/978-3-319-14385-9_4

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