Resolution of the I Ukrainian forum on miscarriages

On May 23–24, 2024, the 1st Ukrainian Forum on Miscarriages took place

Authors

  • T.F. Tatarchuk SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-5498-4143
  • N.P. Honcharuk P.L. Shupyk National Healthcare University of Ukraine; Kyiv City Maternity Hospital No. 1, Kyiv , Ukraine https://orcid.org/0000-0001-7207-3696
  • N.Y. Pedachenko P.L. Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0002-0821-2943
  • D.H. Konkov National Pirogov Memorial Medical University, Vinnytsia, Ukraine https://orcid.org/0000-0002-9375-7509
  • A.M. Kalinchuk Kyiv City Center of Reproductive and Perinatal Medicine, Kyiv, Ukraine
  • E.H. Manzhalii O.O. Bogomolets National Medical University; Ukrainian Liver Foundation; Global Longevity Institute; clinic Verum Expert, Kyiv, Ukraine https://orcid.org/0000-0003-0920-4627
  • T.K. Znamenska SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; Association of Neonatologists of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0001-5402-1622
  • T.M. Tutchenko SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine»; “DILA” Medical Laboratory, Kyiv, Ukraine https://orcid.org/0000-0002-3003-3650
  • M.V. Haytovych O.O. Bogomolets National Medical University, Kyiv, Ukraine

DOI:

https://doi.org/10.18370/2309-4117.2024.73.35-44

Keywords:

Ukrainian Forum on Miscarriages, resolution, pregnancy loss, threatened miscarriage, repeated miscarriage, progestagens, dydrogesterone

Abstract

Today, there is an urgent need to develop and implement a regulatory document on abortion. This is due to the catastrophic state of reproduction of the Ukrainian population – the annual decrease in the number of labor, birth rates and the demographic crisis in Ukraine in general. Pregnancy loss not only causes obstetric complications, but also causes significant damage of the mental health of the woman and her partner, including depression and post-traumatic stress disorder.
This resolution is a joint position of the leading specialists of Ukraine on the issue of miscarriages based on domestic experience, results of randomized controlled trials and meta-analyses, as well as clinical recommendations of scientific societies of the world. The presented information is designed to help improve clinical approaches to the management of miscarriage in today’s conditions, in order to save every pregnancy and to not lose a baby.
During the Forum, the practical issues of diagnosis and treatment of miscarriage, modern management of threatened and habitual miscarriage, hormonal support of pregnant women and the use of progestogens, the influence of the first half of pregnancy on the birth of a healthy child, the impact of liver diseases on the choice of therapy in a pregnant woman, and others issues were considered.
World clinical experience has convincingly proven the high effectiveness of progestogens in the therapy of threatened and repeated miscarriages. However, not all progestogens are equally effective in reducing the risk of miscarriage and live birth in case of threatened miscarriage. Micronized progesterone and dydrogesterone are the most effective. Dydrogesterone differs from progesterone in its mechanism of action and affinity for progesterone receptors. A strong evidence base has been accumulated about a high profile of effectiveness and a low frequency of maternal and fetal complications for dydrogesterone, the use of which is approved by leading foreign associations.
Drug interactions and their effects on the liver should also be taken into account. Drugs that are indicated for pregnant women should be prescribed in the smallest therapeutic dose, which should be effective.

Author Biographies

T.F. Tatarchuk, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work;
Head of the Endocrine Gynecology Department;
chief researcher, Department of Reproductive Health

N.P. Honcharuk, P.L. Shupyk National Healthcare University of Ukraine; Kyiv City Maternity Hospital No. 1, Kyiv

MD, professor, Obstetrics, Gynecology and Perinatology Department;
director

N.Y. Pedachenko, P.L. Shupyk National Healthcare University of Ukraine, Kyiv

MD, professor, Obstetrics, Gynecology and Perinatology Department

D.H. Konkov, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Obstetrics and Gynecology Department No. 1

A.M. Kalinchuk, Kyiv City Center of Reproductive and Perinatal Medicine, Kyiv

Prenatologist, ultrasound doctor, Department of Prenatal Diagnostics

E.H. Manzhalii, O.O. Bogomolets National Medical University; Ukrainian Liver Foundation; Global Longevity Institute; clinic Verum Expert, Kyiv

MD, associate professor, Department of Propedeutics of Internal Medicine;
president;
CEO;
Chief of Hepatology department

T.K. Znamenska, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; Association of Neonatologists of Ukraine, Kyiv

MD, professor, deputy director of perinatal medicine, head of the Neonatology Department;
president

T.M. Tutchenko, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine»; “DILA” Medical Laboratory, Kyiv

PhD, senior researcher, Endocrine Gynecology Department;
Department of Reproductive Health;
Scientific consultant

M.V. Haytovych, O.O. Bogomolets National Medical University, Kyiv

MD, professor, head of the Department of Clinical Pharmacology and Clinical Pharmacy

References

  1. The birth rate in Ukraine has decreased by 28% since the beginning of the Great War. [Internet]. Opendatabot. 2023. Available from: Access mode: https://opendatabot.ua/analytics/birth-crisis-2023.
  2. ESHRE Guideline Group on RPL. The European Society of Human Reproduction and Embryology Guidelines. Hum Reprod Open 2018 Apr 6;2018(2):hoy004. DOI: 10.1093/hropen/hoy004
  3. Keyhan S, Muasher L, Muasher SJ. Chapter 16. Spontaneous Abortion and Recurrent Pregnancy Loss: Etiology, Diagnosis, Treatment. In: Lobo RA, Gershenson DM, Lentz GM, et al., eds. Comprehensive Gynecology. 7th edn. Philadelphia: Elsevier; 2017: 329–347.
  4. WHO Definitions and indicators in family planning and maternal and child health and reproductive health. [Internet]. World Health Organization. 2021. Available from: https://apps.who.int/iris/bitstream/handle/10665/108284/E68459.pdf?seq
  5. Quenby S, GallosI D, Dhillon-Smith RK, et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.Lancet. 2021; 397(10285): 1658–1667. DOI: 10.1016/S0140-6736(21)00682-6.
  6. El Hachem H, Crepaux V, May-Panloup P, et al. Recurrent pregnancy loss: Current perspectives. Int J Womens Health. 2017; 9: 331–345. DOI: 10.2147/IJWH.S100817
  7. Tavoli Z, Mohammadi M, Tavoli A, et al. Quality of life and psychological distress in women with recurrent miscarriage: A comparative study. Health Qual Life Outcomes. 2018; (1). DOI: 10.1186/s12955-018-0982-z
  8. Lok IH, Neugebauer R. Psychological morbidity following miscarriage. Best Pract Res Clin Obstet Gynaecol. 2007; 21(2): 229–247. DOI: 10.1016/j.bpobgyn.2006.11.007
  9. What is the psychological impact of miscarriage? [Internet]. FIGO, 2018. Available from: https://www.figo.org/news/what-psychological-impact-miscarriage.
  10. Bashiri A, Harlev A, Agarwal A. Recurrent Pregnancy Loss: Evidence-Based Evaluation. Diagnosis and Treatment. 2016 Jan. DOI:10.1007/978-3-319-27452-2
  11. Arias-Sosa LA, Acosta ID, Lucena-Quevedo E, et al. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss. J Assist Genet 2018 Mar;35(3):355–366. DOI: 10.1007/s10815-017-1108-y
  12. Macklon NS, Geraedts JPM, Fauser BCJM. Conception to ongoing pregnancy: The “black box” of early pregnancy loss. Hum Reprod Update. 2002;8(4):333–343. DOI: 10.1093/humupd/8.4.333
  13. Ectopic pregnancy and miscarriage: diagnosis and initial management. NICE guideline [NG126]. [Internet]. NICE. 2019. April 17. Available from: https://www.nice.org.uk/guidance/ng126
  14. Recurrent pregnancy loss. Guideline of the European Society of Human Reproduction and Embryology 2023. [Internet]. ESHRE. 2023. Available from: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss.
  15. Diagnosis and treatment of luteal phase deficiency: a committee opinion (2021). [Internet]. ASMR. 2021 Available from: https://www.asrm.org/practice-guidance/practice-committee-documents/diagnosis-andtreatment-of-luteal-phase-deciency-a-committee-opinion-2021/
  16. Stilley J.A.W., Birt JA, Sharpe-Timms KL. Cellular and molecular basis for endometriosis-associated infertility. Cell. Tissue Res. 2012; 349(3):849–862. DOI: 10.1007/s00441-011-1309-0.
  17. Hill CJ, Fakhreldin M, Maclean A, et al. Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications. J. Clin. Med. 2020; 9(6):1905. DOI: 10.3390/jcm9061905.
  18. Hodgson RM, Lee HL, Wang R et al. Interventions for endometriosis-related infertility: a systematic review and network meta-analysis. Fertil Steril.2020 Feb; 113(2): 374–382. DOI: 10.1016/j.fertnstert.2019.09.031.
  19. Becker C.M., Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod. Open. 2022 Feb 26; 2022 (2):hoac009. DOI: 10.1093/hropen/hoac009.
  20. International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023. [Internet]. Monash University. 2023. Available from: https://www.monash.edu/__data/assets/pdf_file/0003/3371133/PCOS-Guideline-Summary-2023.pdf.
  21. Toth B, Wurfel W, Bohlmann M, et al. Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050). Geburtshilfe Frauenheilkd. 2018; 78(4):364–381. DOI:10.1055/a-0586-4568
  22. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Progesterone support of the luteal phase and in the first trimester. [Internet]. Available from: https://ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Progesterone-support-of-the.pdf?ext=.pdf
  23. American Society for Reproductive Medicine. Fertility and Sterility. [Internet]. Published by Elsevier Inc. 2015. Vol. 103, No. 4, April. Available from: http://dx.doi.org/10.1016/j.fertnstert.2014.12.12
  24. Li YH, Marren A. Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice. The Royal Australian College of General Practitioners. AJGP VOL. 47, NO. 7, JULY 2018. DOI: 10.31128/AJGP-01-18-4459
  25. Shehata H, Elfituri A, Doumouchtsis SK. FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first-trimester miscarriage. Int J Gynecol Obstet. 2023. 161:3–16. DOI: 10.1002/ijgo.14717.
  26. Zhao Y, D’Souza R, Gao Y, et al. Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta-analysis. Acta Obstet Gynecol Scand. 2024 Mar 13. DOI: 10.1111/aogs.14829
  27. Colombo D, Ferraboschi P, Prestileo P, Toma L. A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy. J. Steroid Biochem. Mol. Biol. 2006;98:56–62. DOI: 10.1016/j.jsbmb.2005.07.009.
  28. Stanczyk FZ, Hapgood JP, Winer S, Mishell JrD.R. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr. Rev. 2013;34:171–208 DOI: 10.1210/er.2012-1008.
  29. Rižner TL, Brožič P, Doucette C, et al. Selectivity and potency of the retroprogesterone dydrogesteronein vitro. Steroids. 2011;76:607–615 DOI: 10.1016/j.steroids.2011.02.043
  30. Schindler AE, Campagnoli C, Druckmann R, et al. Classification and pharmacology of progestins. Maturitas. 2003; 46: S7–S16. DOI: 10.1016/j.maturitas.2008.11.013
  31. Chinese Association of Reproductive Medicine. Standards and Specifications Clinical practice guidelines for progesterone in pregnancy maintenance and luteal phase support. Chin J Reprod Contracep 2021;41(2):95–105. DOI: 10.1111/jebm.12346
  32. Israel Guidelines Recurrent Pregnancy Loss: Bashiri A, Orbito R, Carp H, et al. Recurrent Pregnancy Loss. [Internet]. Position Paper Number 215. 2021. Available online: https://ima-contentfiles.s3.amazonaws.com/Ne167_pregnencyLost.pdf
  33. Obstetrical and Gynaecological Society of Malaysia. [Internet]. OGSM. 2020. Available from: https://ogsm.org.my/guidelines_gen.php.
  34. Arab H, Alharbi AJ, Oraif A, et al. The Role Of Progestogens In Threatened And Idiopathic Recurrent Miscarriage. International Journal of Women’s Health. 2019:11:589–596. DOI: 10.2147/IJWH.S224159
  35. Schindler AE, Carp H, Druckmann R, et al. European Progestin Club Guidelines for prevention and treatment of threatened or recurrent (habitual) miscarriage with progestogens. Gynecol Endocrinol 2015;31(6):447–449. DOI: 10.3109/09513590.2015.1017459
  36. FOGSI position statement on the use of progestogens. [Internet]. Available from: https://www.fogsi.org/wp-content/uploads/2015/11/Progesterone-position-paper-Oct-2015.pdf.
  37. Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy. Fertil Steril. 2008 Nov. 90(5 Suppl):S206–12. DOI: 10.1016/j.fertnstert.2008.08.049
  38. ACOG’s Guide to Managing Miscarriage: Follow Patient Preference. Updated clinical management of early pregnancy loss focuses on patient choice / Ed. S. Gupta. [Internet]. Medpagetoday, 04.22.2015. Available from: http://www.medpagetoday.com/ OBGYN/Pregnancy/51131
  39. Casikar I, Riemke TJ, Alhamdan D, Condous G. Expectant management of spontaneous first- trimester miscarriage: prospective validation of the ‘2-week rule. Ultrasound. Obstet. Gynecol. 2010. 35(2):223–7. DOI: 10.1002/uog.7486
  40. Coutinho CM, Sotiriadis A, Odibo A, et al. ISUOG Practice Guidelines on the role of ultrasound in the prediction of spontaneous preterm birth. Ultrasound Obstet Gynecol. 2022 60 (3):435–56. DOI: 10.1002/uog.26020.
  41. Barnhart KT, Katz I, Hummel A, Gracia CR. Presumed diagnosis of ectopic pregnancy. Obstet Gynecol. 2002 Sep. 100(3):505–10. DOI: 10.1016/s0029-7844(02)02142-7
  42. Lewis R. First Do No Harm: Guidelines Define a Nonviable Pregnancy. [Internet]. Medscape Medical News. 2024 12 Sep. Available from: http://www.medscape.com/viewarticle/812346.
  43. Doubilet PM, Benson CB, Bourne T, Blaivas M, et al. Diagnostic Criteria for Nonviable Pregnancy Early in the First Trimester. N Engl J Med. 2013 Oct 10. 369(15):1443–51. DOI: 10.1056/NEJMra1302417.
  44. Huchon C, Deffieux X, Beucher G, et al Pregnancy loss: French clinical practice guidelines. Eur J Obstet Gynecol Reprod Biol. 2016 Jun 201:18–26. DOI: 10.1016/j.ejogrb.2016.02.01
  45. Ghosh J, Papadopoulou A, Devall AJ, et al. Methods for managing miscarriage: a network meta-analysis. Cochrane Database Syst Rev. 2021 Jun 1;6(6):CD012602. DOI: 10.1002/14651858.CD012602.pub2.
  46. Zgheib NK, Branch RA. Drug metabolism and liver disease: a drug-gene-environment interaction. Drug MetabRev. 2017 Feb; 49(1):35–55. DOI: 10.1080/03602532.2016.1271807.
  47. Almazroo OA, Miah MK, Venkataramanan R. Drug Metabolism in the Liver. Clin Liver Dis. 2017 Feb;21(1):1–20. DOI: 10.1016/j.cld.2016.08.001.
  48. Garcia ALA. Effect of Pregnancy on Pre-existing Liver Disease Physiological Changes During Pregnancy. Annals of Hepatology. 2006 Jul-Sep;5(3):184-6.
  49. Liver Tox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. [Internet]. Progestins 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548237/.
  50. Sukhikh G, Baranov I, Melnichenko G, et al. Lotus I: A Phase III randomized controlled trial of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization, with focus on the Russian subpopulation. Scientific and Practical Journal, Obstetrics and Gynecology. 2017 Jul 25. DOI: 10.18565/aig.2017.7.75-95.
  51. Tournaye H, Sukhikh GT, Kahler E, Griesinger G, et al. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Human Reproduction. 2017; 32(5): 1019-1027. DOI: 10.1093/humrep/dex023
  52. Instruction for the medical use of the drug DufastonR. [Internet]. Available from: https://mozdocs.kiev.ua/likiview.php?id=15524.
  53. Griesinger G, Blockeel C, Kahler E, et al. Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis. PLoS ONE 2020;15(11):e241044. DOI: 10.1371/journal.pone.0241044
  54. Griesinger G, Blockeel C, Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril 2018;110(4S):O212. DOI: 10.1016/j.fertnstert.2018.03.034
  55. Griesinger G, Blockeel C, Sukhikh GT, et al. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod 2018;33(12):2212–21. DOI: 10.1093/humrep/dey306
  56. Podzolkova N, Tatarchuk T, Doshchanova A, et al. Dydrogesterone treatment for menstrual-cycle regularization in routine clinical practice: a multicenter observational study. Reproductive Endocrinology. 2016;32(3):246–9. DOI: 10.3109/09513590.2015.1115832.
  57. Katalinic A, Noftz MR, Garcia-Velasco JA, et al. No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis. Hum Reprod Open. 2024 Jan 23;2024(1):hoae004.DOI: 10.1093/hropen/hoae004.

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Published

2024-10-18

How to Cite

Tatarchuk, T., Honcharuk, N., Pedachenko, N., Konkov, D., Kalinchuk, A., Manzhalii, E., Znamenska, T., Tutchenko, T., & Haytovych, M. (2024). Resolution of the I Ukrainian forum on miscarriages: On May 23–24, 2024, the 1st Ukrainian Forum on Miscarriages took place. REPRODUCTIVE ENDOCRINOLOGY, (73), 35–44. https://doi.org/10.18370/2309-4117.2024.73.35-44

Issue

No. 73 (2024)

Section

Pregnancy and childbirth

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