To the content
4 . 2023

FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first-trimester miscarriage

Abstract



Funding. FIGO received an unrestricted educational grant from Abbott Pharmaceuticals.

Conflict of interest. Ramesh Ganapathy declares a UK patent granted for medical apparatus, unrelated to the present publication. Moshe Hod declares a lecture honorarium from Abbott Pharmaceuticals. All other authors have no conflicts of interest to declare.

Сontributios. All authors performed different parts of the analysis, drafted the manuscript, reviewed the papers from the searches, contributed to data interpretation, and revised the manuscript. The final version was approved by all authors.

Data availability. Data sharing not applicable for this article as no datasets were generated or analyzed during the current study.

Shehata H., Elfituri A., Doumouchtsis S.K., Zini M.E., Ali A., Jan H., Ganapathy R., Divakar H., Hod M. FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first-trimester miscarriage. Int J Gynaecol Obstet. 2023 Apr; 161 Suppl 1: 3–16.

DOI: https://doi.org/10.1002/ijgo.14717

References

1. Royal College of Obstetricians and Gynaecologists. The Investigation and Treatment of Couples with Recurrent Miscarriage (Green-top Guideline No. 17). RCOG Press, 2011.

2. Practice Committee of the American Society for reproductive medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012; 98: 1103–11.

3. Swyer G.I., Daley D. Progesterone implantation in habitual abortion. Br Med J. 1953; 1: 1073–7.

4. Society for Maternal- Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012; 206: 376–86.

5. Meis P.J., Klebanoff M., Thom E., et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxy-progesterone caproate. N Engl J Med. 2003; 348: 2379–85.

6. Szekeres-Bartho J., Par G., Dombay G., Smart Y.C., Volgyi Z. The antiabortive effect of progesterone-induced blocking factor in mice is manifested by modulating NK activity. Cell Immunol. 1997; 177: 194–9.

7. Romero R., Nicolaides K., Conde-Agudelo A., 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 meta-analysis of individual patient data. Am J Obstet Gynecol. 2012; 206 (2): 124.e1–19.

8. O’Brien J.M., Lewis D.F. Prevention of preterm birth with vaginal progesterone or 17-alpha-hydroxy-progesterone caproate: a critical examination of efficacy and safety. Am J Obstet Gynecol. 2016; 214: 45–56.

9. Romero R., Stanczyk F.Z. Progesterone is not the same as 17a-hydroxy-progesterone caproate: implications for obstetrical practice. Am J Obstet Gynecol. 2013; 208: 421–6.

10. Ruddock N.K., Shi S.Q., Jain S., et al. Progesterone, but not 17-alpha-hydroxy-progesterone caproate, inhibits human myometrial contractions. Am J Obstet Gynecol. 2008; 199 (4): 391.e1–7.

11. Saccone G., Schoen C., Franasiak J.M., Scott R.T. Jr, Berghella V. Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril. 2017; 107: 430–8.e3.

12. Guyatt G.H., Oxman A.D., Vist G.E., et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 336 (7650): 924–6.

13. Coomarasamy A., Williams H., Truchanowicz E., et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015; 373: 2141–8.

14. El-Zibdeh M.Y. Dydrogesterone in the reduction of recurrent spontaneous abortion. J Steroid Biochem Mol Biol. 2005; 97: 431–4.

15. Corner G.W. Sr. The early history of progesterone. Gynecol Invest. 1974; 5: 106–12.

16. Regidor P.A. The clinical relevance of progestogens in hormonal contraception: present status and future developments. Oncotarget. 2018; 9: 34 628–38.

17. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005; 8 (suppl 1): 3–63.

18. Zutshi V., Rathore A., Sharma K. (eds). Hormones in Obstetrics and Gynaecology. 2nd ed. New Delhi: Jaypee, 2005.

19. Cometti B. Pharmaceutical and clinical development of a novel progesterone formulation. Acta Obstet Gynecol Scand. 2015; 94 (suppl 161): 28–37.

20. Shehata H., Ali A., Silva-Edge M., et al. Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? A cohort study and systematic review of the literature. BMJ Open. 2022; 12: e059519.

21. Casper R.F. Luteal phase support for frozen embryo transfer cycles: intramuscular or vaginal progesterone? Fertil Steril. 2014; 101: 627–8.

22. Malassiné A., Frendo J.L., Evain-Brion D. A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update. 2003; 9: 531–9.

23. Daya S., Ward S., Burrows E. Progesterone profiles in luteal phase defect cycles and outcome of progesterone treatment in patients with recurrent spontaneous abortion. Am J Obstet Gynecol. 1988; 158: 225–32.

24. Critchley H.O., Jones R.L., Lea R.G., et al. Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy. J Clin Endocrinol Metab. 1999; 84: 240–8.

25. Mor G., Aldo P., Alvero A.B. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. 2017; 17: 469–82.

26. Csapo A.I., Pulkkinen M.O., Ruttner B., Sauvage J.P., Wiest W.G. The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies. Am J Obstet Gynecol. 1972; 112: 1061–7.

27. Babalioğlu R., Varol F.G., Ilhan R., Yalçin O., Cizmecioğlu F. Progesterone profiles in luteal-phase defects associated with recurrent spontaneous abortions. J Assist Reprod Genet. 1996; 13: 306–9.

28. Li T.C., Spuijbroek M.D., Tuckerman E., Anstie B., Loxley M., Laird S. Endocrinological and endometrial factors in recurrent miscarriage. BJOG. 2000; 107: 1471–9.

29. Haas D.M., Hathaway T.J., Ramsey P.S. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev. 2018; 10 (10): CD003511.

30. Hussain M., El-Hakim S., Cahill D.J. Progesterone supplementation in women with otherwise unexplained recurrent miscarriages. J Hum Reprod Sci. 2012; 5: 248–51.

31. Katalinic A., Shulman L.P., Strauss J.F., Garcia-Velasco J.A., van den Anker J.N. A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis. Reprod Biomed Online. 2022; 45: 365–73.

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

33. Omar M.H., Mashita M.K., Lim P.S., Jamil M.A. Dydrogesterone in threatened abortion: pregnancy outcome. J Steroid Biochem Mol Biol. 2005; 97: 421–5.

34. Schindler A.E., Campagnoli C., Druckmann R., et al. Classification and pharmacology of progestins. Maturitas. 2003; 46 (suppl 1): S7–16.

35. National Institute for Health and Care Excellence. Ectopic pregnancy and miscarriage: diagnosis and initial management. NICE guideline [NG126]. Published 17 April 2019. Last updated 24 November 2021.

36. Cicinelli E., Cignarelli M., Sabatelli S., et al. Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril. 1998; 69: 471–3.

37. Haas D.M., Ramsey P.S. Progestogen for preventing miscarriage. Cochrane Database Syst Rev. 2013; 10: CD003511.

38. Statement of Retraction. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. J Matern Fetal Neonatal Med. 2020; 33: 1073.

39. Kashanian M., KaramiAbd T., Sheikhansari N., AminiMoghaddam S., Jangjoo S. Efficacy of daily rectal micronized progesterone for prevention of preterm delivery: a randomized clinical trial. J Matern Fetal Neonatal Med. 2022; 35: 122–8.

40. Kumar P., Magon N. Hormones in pregnancy. Niger Med J. 2012; 53: 179–83.

41. Aboulghar M.M., El-Faissal Y., Kamel A., et al. The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial. BMC Pregnancy Childbirth. 2020; 20: 351.

42. Aghsa M.M., Rahmanpour H., Bagheri M., Davari-Tanha F., Nasr R. A randomized comparison of the efficacy, side effects and patient convenience between vaginal and rectal administration of Cyclogest® when used for luteal phase support in ICSI treatment. Arch Gynecol Obstet. 2012; 286: 1049–54.

43. Khrouf M., Slimani S., Khrouf M.R., et al. Progesterone for luteal phase support in In vitro fertilization: comparison of vaginal and rectal pessaries to vaginal capsules: a randomized controlled study. Clin Med Insights Womens Health. 2016; 9: 43–7.

44. Beigi A., Esmailzadeh A., Pirjani R. Comparison of risk of preterm labor between vaginal progesterone and 17-alpha-hydroxy-progesterone caproate in women with threatened abortion: a randomized clinical trial. Int J Fertil Steril. 2016; 10: 162–8.

45. Haghighi L., Rashidi M., Najmi Z., et al. Comparison of intramuscular progesterone with oral nifedipine for treating threatened preterm labor: a randomized controlled trial. Med J Islam Repub Iran. 2017; 31: 56.

46. Duan L., Yan D., Zeng W., Yang X., Wei Q. Effect of progesterone treatment due to threatened abortion in early pregnancy for obstetric and perinatal outcomes. Early Hum Dev. 2010; 86: 41–3.

47. Saccone G., Khalifeh A., Elimian A., et al. Vaginal progesterone vs intramuscular 17a-hydroxy-progesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017; 49: 315–21.

48. Samson F.D., Merriman A.L., Tate D.L., Apostolakis-Kyrus K., Gomez L.M. Adjuvant administration of 17-a-hydroxy-progesterone caproate in women with three or more second trimester pregnancy losses undergoing cervical cerclage is no more effective than cerclage alone. J Perinat Med. 2018; 46: 155–61.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITORS
CHIEF EDITOR
Sukhikh Gennadii Tikhonovich
Academician of the Russian Academy of Medical Sciences, V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Moscow
CHIEF EDITOR
Kurtser Mark Arkadievich
Academician of the Russian Academy of Sciences, MD, Professor, Head of the Obstetrics and Gynecology Subdepartment of the Pediatric Department, N.I. Pirogov Russian National Scientific Research Medical University, Ministry of Health of the Russian Federation
CHIEF EDITOR
Radzinsky Viktor Evseevich
Corresponding Member of the Russian Academy of Sciences, MD, Professor, Head of the Subdepartment of Obstetrics and Gynecology with a Course of Perinatology of the Medical Department in the Russian People?s Friendship University

Journals of «GEOTAR-Media»