A systematic review of dydrogesterone for the treatment of threatened miscarriage

Howard Carp, Howard Carp

Abstract

The objective of this systematic review was to assess whether the orally acting progestagen, dydrogesterone lowers the incidence of miscarriage in women with threatened miscarriage. A computerized search was performed in Medline, Embase, and Ovid Medline for original reports with the product name 'Duphaston' or 'dydrogesterone', and limited to clinical human data. Twenty-one reports of dydrogesterone treatment were identified with 1380 patients. Five randomized trials were identified, including 660 women who fulfilled the criteria for meta-analysis. The number of subsequent miscarriages or continuing pregnancies per randomized woman was compared in women receiving dydrogesterone compared to standard bed rest or placebo intervention. There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women [odds ratio for miscarriage 0.47, (CI = 0.31-0.7), 11% absolute reduction in the miscarriage rate]. The adverse and side effects were summarized in all 21 reports, and seemed to be minimal. Although all the predictive and confounding factors could not be controlled for, the results of this systematic review show a significant reduction of 47% in the odds for miscarriage when dydrogesterone is compared to standard care indicating a real treatment effect.

Figures

Figure 1.
Figure 1.
Flow chart for inclusion or exclusion of studies.
Figure 2.
Figure 2.
Common Odds Ratio for randomized studies (fixed effects).

References

    1. Weiss JL, Malone FD, Vidaver J, Ball RH, Nyberg DA, Comstock CH, Hankins GD, et al. FASTER Consortium. Threatened abortion: A risk factor for poor pregnancy outcome, a population-based screening study. Am J Obstet Gynecol. 2004;190:745–750.
    1. Everett C. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. BMJ. 1997;315:32–34.
    1. Szekeres-Bartho J, Barakonyi A, Par G, Polgar B, Palkovics T, Szereday L. Progesterone as an immunomodulatory molecule. Int Immunopharmacol. 2001;1:1037–1048.
    1. 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;7:723–725.
    1. 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;102:364–369.
    1. Csapo AI, Pulkkinen M. Indispensability of the human corpus luteum in the maintenance of early pregnancy. Luteectomy evidence. Obstet Gynecol Surv. 1978;33:69–81.
    1. Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril. 1998;69:96–101.
    1. Di Renzo GC, Mattei A, Gojnic M, Gerli S. Progesterone and pregnancy. Curr Opin Obstet Gynecol. 2005;17:598–600.
    1. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2003;46(Suppl 1):S7–S16.
    1. Czajkowski K, Sienko J, Mogilinski M, Bros M, Szczecina R, Czajkowska A. Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone. Fertil Steril. 2007;87:613–618.
    1. Ehrenskjöld ML, Bondo B, Weile F. [Treatment of threatened abortion with dydrogesterone] Ugeskr Laeg. 1967;129:1678–1679. [Article in Danish]
    1. Mistò A. [Experiences with 6-dehydro-retroprogesterone int the treatment of placental insufficiency] Ann Ostet Ginecol Med Perinat. 1967;89:102–112. [Article in Italian]
    1. El-Zibdeh MY, Yousef LT. Dydrogesterone support in threatened miscarriage. Maturitas. 2009;65(Suppl 1):S43–S46.
    1. Omar MH, Mashita MK, Lim PS, Jamil MA. Dydrogesterone in threatened abortion: pregnancy outcome. J Steroid Biochem Mol Biol. 2005;97:421–425.
    1. Pandian RU. Dydrogesterone in threatened miscarriage: a Malaysian experience. Maturitas. 2009;65(Suppl 1):S47–S50.
    1. Vincze E, Molnár BG, Földesi I, Pál A. Treatment possibilities for threatened abortion using progesterone and progesterone-type drugs. J Hungarian Gynaecol. 2006;69:281–284.
    1. Bashmakova NV, Melkozerova OA, Vinokurova EA, Pepekyeva NA. Health condition of infants and born children to mothers with threatened miscarriages. Reproduction problems. 2004;2:1–3. [Article in Russian]
    1. Eggimann UH, Thürig E, Moser H, Bossi E. [Threatened abortion: patient characteristics, treatment results and consequences for the child] Schweiz Med Wochenschr. 1979;109:288–292. [Article in German]
    1. Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. Am J Reprod Immunol. 2005;53:166–171.
    1. Kalinka J, Radwan M. The impact of dydrogesterone supplementation on serum cytokine profile in women with threatened abortion. Am J Reprod Immunol. 2006;55:115–121.
    1. Manukhin IB, Gevorkyan MA, Minkina GN, Manukhina EI. Efficacy of Duphaston in treating threatened miscarriage in early stages of pregnancy. Reprod Issues. 2004;6:63–64.. [Article in Russian]
    1. Pelinescu-Onciul D. Subchorionic hemorrhage treatment with dydrogesterone. Gynecol Endocrinol. 2007;23(Suppl 1):77–81.
    1. Yamamoto K. [Study of 6-dehydro-retro-progesterone; especially in comparison with the effect of 17-alpha-ethynyl-19-nortestosterone] Zasshi Tokyo Ika Daigaku. 1968;26:385–403. [Article in Japanese]
    1. Chang IW. Clinical trial of isopregnenone, a new progestational agent. Preliminary study. Med Ann Dist Columbia. 1962;31:402–405.
    1. Gronow MJ. Ovarian hyperstimulation for successful in vitro fertilization and embryo transfer. Acta Obstet Gynecol Scand Suppl. 1985;131:1–80.
    1. Ketkar S. Role of dydrogesterone in threatened abortion. Obs Gynae Today. 2008;12:197–199.
    1. Aydar CK, Greenblatt RB. 6-Dehydro-retroprogesterone (duphaston) an interesting progesterone-like compound. Int J Fertil. 1964;9:585–595.
    1. Backer MH., Jr Isopregnenone (Duphaston): a new progestational agent. Obstet Gynecol. 1962;19:724–729.
    1. Gellé P, Schaeffer P. [Apropos of the use of dydrogesterone in gynecology and obstetrics; clinical experience] Bull Fed Soc Gynecol Obstet Lang Fr. 1965;17:369–370. [Article in French]
    1. Jamain M, Grenet C. [Utilization of 6-dehydro-retroprogesterone in obstetrics: indications; results] Bull Fed Soc Gynecol Obstet Lang Fr. 1969;21:26–31. [Article in French]
    1. Sureau C, Combourieu P. [Clinical Study Of 6-dehydro-retroprogesterone (dydrogesterone)] Bull Fed Soc Gynecol Obstet Lang Fr. 1964;16:263–269. [Article in French]
    1. Wahabi HA, Fayed AA, Esmaeil SA, Al Zeidan RA. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2011;12:CD005943.
    1. 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.
    1. 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;1034:200–210.
    1. Queisser-Luft A. Dydrogesterone use during pregnancy: overview of birth defects reported since 1977. Early Hum Dev. 2009;85:375–377.
    1. Arck PC, Rücke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, Blois SM, et al. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reprod Biomed Online. 2008;17:101–113.
    1. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage–results from a UK-population-based case-control study. BJOG. 2007;114:170–186.
    1. Gracia CR, Sammel MD, Chittams J, Hummel AC, Shaunik A, Barnhart KT. Risk factors for spontaneous abortion in early symptomatic first-trimester pregnancies. Obstet Gynecol. 2005;106:993–999.
    1. Achiron R, Tadmor O, Mashiach S. Heart rate as a predictor of first-trimester spontaneous abortion after ultrasound-proven viability. Obstet Gynecol. 1991;78:330–334.
    1. 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;21:331–335.
    1. 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;81:263–266.
    1. 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;7:165–169.
    1. Bennett GL, Bromley B, Lieberman E, Benacerraf BR. Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography. Radiology. 1996;200:803–806.
    1. Abraham GE, Maroulis GB, Marshall JR. Evaluation of ovulation and corpus luteum function using measurements of plasma progesterone. Obstet Gynecol. 1974;44:522–525.
    1. la Marca A, Morgante G, De Leo V. Human chorionic gonadotropin, thyroid function, and immunological indices in threatened abortion. Obstet Gynecol. 1998;92:206–211.
    1. Florio P, Luisi S, D’Antona D, Severi FM, Rago G, Petraglia F. Maternal serum inhibin A levels may predict pregnancy outcome in women with threatened abortion. Fertil Steril. 2004;81:468–470.
    1. Schmidt T, Rein DT, Foth D, Eibach HW, Kurbacher CM, Mallmann P, Römer T. Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy. Eur J Obstet Gynecol Reprod Biol. 2001;97:168–173.
    1. Fiegler P, Katz M, Kaminski K, Rudol G. Clinical value of a single serum CA-125 level in women with symptoms of imminent abortion during the first trimester of pregnancy. J Reprod Med. 2003;48:982–988.

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