Comparative assessment of the efficacy of micronized progesterone medications in the IVF programs

Mayasina E.N., Buev Yu.E., Askerov R.A., Yamalyeva N.Sh., Kichigina E.A., Kornilova A.S., Salimov D.F.

Clinical Institute of Reproductive Medicine, Yekaterinburg, Russia

Ovarian stimulation in the in vitro fertilization (IVF) programs is accompanied by a defect in the luteal phase of the cycle, therefore hormonal support after embryo transfer into the uterine cavity is an integral part of the treatment. Vaginal administration is the most common route for the progesterone delivery.
Objective: To compare efficacy and tolerability of two forms of vaginal micronized progesterone, namely capsules (Utrogestan, Besins Healthcare) and gel (Miragel, Vertex JSC), in the IVF programs.
Materials and methods: The study included 309 patients: the patients of the first group (n=154) received micronized progesterone in the form of a vaginal gel at a dose of 90 mg per day, the patients of the second group (n=155) were administered micronized progesterone in capsules 200 mg 3 times a day vaginally. Efficacy was assessed using the following parameters: clinical pregnancy rate, early pregnancy loss rate, live birth rate. The medication tolerability was compared using the assessment of the patients’ questionnaires.
Results: Clinical pregnancy rate in the first group was 59.1%, and it was 55.2% in the second group; early pregnancy loss rate was 14.2% and 15.1%, respectively; live birth rate in the first group was 49.4%, and it was 45.2% in the second group. There were no statistically significant differences between the groups. The rate of premature births in the first group was 0%, and it was 7.1% in the second group. According to the patients’ survey, micronized progesterone in the form of a gel was better tolerated.
Conclusion: The comparative assessment of the vaginal administration of micronized progesterone in the form of gel and capsules demonstrated high efficacy of the medication. The vaginal gel was better tolerated and more convenient for the patients, according to the survey. Miragel can be administered to support the luteal phase in the IVF programs.

Authors’ contributions: Mayasina E.N. – developing the concept and design of the study; Mayasina E.N., Askerov R.A., Buev Yu.E., Yamalyeva N.Sh., Kornilova A.S., Kichigina E.A. – collecting and processing the material; Salimov D.F. – statistical analysis of the data; Askerov R.A. – editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has not been sponsored.
Ethical Approval: The study was approved by the Ethical Review Board of the Clinical Institute of Reproductive Medicine, Yekaterinburg.
Patient Consent for Publication: The patients provided an informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Mayasina E.N., Buev Yu.E., Askerov R.A., Yamalyeva N.Sh., Kichigina E.A., Kornilova A.S., Salimov D.F. Comparative assessment of the efficacy of  micronized progesterone medications in the IVF programs.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (3): 133-140 (in Russian)
https://dx.doi.org/10.18565/aig.2024.38

Keywords

progesterone
vaginal progesterone gel
luteal phase support
IVF
in vitro fertilization
infertility
ART
assisted reproductive technologies

References

  1. Регистр ВРТ. Отчет за 2021 год. Российская ассоциация репродукции человека. 29c. Доступно по: https://www.rahr.ru/d_registr_otchet/RegistrVRT_2021.pdf [Registr VRT. Otchet za 2021 god. Rossiiskaya assotsiatsiya reproduktsii cheloveka. 29p. Available at: https://www.rahr.ru/d_registr_otchet/RegistrVRT_2021.pdf (in Russian)].
  2. van der Linden M., Buckingham K., Farquhar C., Kremer J.A., Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst. Rev. 2015; 2015(7): CD009154. https://dx.doi.org/10.1002/14651858.CD009154.pub3.
  3. Министерство здравоохранения Российской Федерации. Клинические рекомендации «Женское бесплодие». 2021. Доступно по: https://cr.minzdrav.gov.ru/recomend/641_1 [Ministry of Health of the Russian Federation. Clinical guidelines "Women’s infertility". 2021. Available at: https://cr.minzdrav.gov.ru/recomend/641_1 (in Russian)].
  4. Zhao J., Hao J., Li Y. Individualized luteal phase support after fresh embryo transfer: unanswered questions, a review. Reprod. Health. 2022; 19(1): 19. https://dx.doi.org/10.1186/s12978-021-01320-7.
  5. Pritts E.A., Atwood A.K. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum. Reprod. 2002; 17(9): 2287-99. https://dx.doi.org/10.1093/humrep/17.9.2287.
  6. Mizrachi Y., Raziel A., Weissman A. When can we safely stop luteal phase support in fresh IVF cycles? A literature review. Front. Reprod. Health. 2020; 2: 610532. https://dx.doi.org/10.3389/frph.2020.610532.
  7. Greenbaum S., Athavale A., Klement A.H., Bentov Y. Luteal phase support in fresh and frozen embryo transfers. Front. Reprod. Health. 2022; 4: 919948. https://dx.doi.org/10.3389/frph.2022.919948.
  8. Child T., Leonard S.A., Evans J.S., Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod. Biomed. Online. 2018; 36(6): 630-45. https://dx.doi.org/10.1016/j.rbmo.2018.02.001.
  9. Shoham G., Leong M., Weissman A. 10-year follow-up on the practice of luteal phase support using worldwide web‐based surveys. Reprod. Biol. Endocrinol. 2021; 19(1): 15. https://dx.doi.org/10.1186/s12958-021-00696-2.
  10. Назаренко Т.А., Зыряева Н.А., Магамадова М.У. Эффективность гестагенов в зависимости от их состава и способа введения. Проблемы репродукции. 2013; 2: 20-5. [Nazarenko T.A., Zyriaeva N.A., Magamadova M.U. Gestagens efficacy according to their composition and the route of administration. Russian Journal of Human Reproduction. 2013; (2): 20‑5. (in Russian)].
  11. Сыркашева А.Г., Петросян Я.А., Долгушина Н.В. Гестагены в программах вспомогательных репродуктивных технологий. Гинекология. 2019; 21(2): 76-9. [Syrkasheva A.G., Petrosyan Ya.A., Dolgushina N.V. Gestagens in assisted reproductive technology programs. Gynecology. 2019; 21(2): 76-9. (in Russian)]. https://dx.doi.org/10.26442/20795696.2019.2.190238.
  12. Корнеева И.Е., Камилова Д.П., Тапильская Н.И., Маясина Е.Н., Фаткуллина Л.С., Чибисова А.Н., Гараева Г.В., Лазарева Л.М. Резолюция Совета экспертов в области акушерства и гинекологии «Новые возможности поддержки лютеиновой фазы препаратами прогестерона в рамках импортозамещения». Акушерство и гинекология. 2024; 1: 167-72. [Korneeva I.E., Kamilova D.P., Tapilskaya N.I., Mayasina E.N., Fatkullina L.S., Chibisova A.N., Garayeva G.V., Lazareva L.M. Resolution of the Council of experts in obstetrics and gynecology «New possibilities of luteal phase support with progesterone preparations in the framework of import substitution». Obstetrics and Gynecology. 2024; (1): 167-72. (in Russian)]. https://dx.doi.org/10.18565/aig.2024.15.
  13. Campaña-Seoane M., Peleteiro A., Laguna R., Otero-Espinar F.J. Bioad-hesive emulsions for control release of progesterone resistant to vaginal fluids clearance. Int. J. Pharm. 2014; 477(1-2): 495-505. https://doi.org/10.1016/j.ijpharm.2014.10.066.
  14. Gupta S., Gabrani R., Ali J., Dang S. Exploring novel approaches to vag-inal drug delivery. Recent Pat. Drug Deliv. Formul. 2011; 5(2): 82-94. https://dx.doi.org/10.2174/187221111795471418.
  15. Michnova L., Dostal J., Kudela M., Hamal P., Langova K. Vaginal use of micronized progesterone for luteal support. A randomized study comparing Utrogestan® and Crinone® 8. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2017; 161(1): 86-91. https://dx.doi.org/10.5507/bp.2017.007.
  16. Маясина Е.Н., Буев Ю.Е., Аскеров Р.А., Ямалыева Н.Ш., Кичигина Е.А., Корнилова А.С., Салимов Д.Ф. Сравнительный анализ эффективности вагинальных форм прогестерона в программах экстракорпорального оплодотворения. Проблемы репродукции. 2023; 29(5): 54-9. [Mayasina E.N., Buev Yu.E., Askerov R.A., Yamalyeva N.Sh., Kichigina E.A., Kornilova A.S., Salimov D.F. Comparative analysis of the effectiveness of vaginal forms of progesterone in IVF programs. Russian Journal of Human Reproduction. 2023; 29(5): 54-9. (in Russian)]. https://doi.org/10.17116/repro20232904154.
  17. Penzias A.S. Luteal phase support. Fertil. Steril. 2002; 77(2): 318-23. https://dx.doi.org/10.1016/s0015-0282(01)02961-2.
  18. Beckers N.G., Macklon N.S., Eijkemans M.J., Ludwig M., Felberbaum R.E., Diedrich K. et al. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist gotreatment. J. Clin. Endocrinol. Metab. 2003; 88(9): 4186-92. https://doi.org/10.1210/jc.2002-021953.
  19. Connell M.T., Szatkowski J.M., Terry N., DeCherney A.H., Propst A.M., Hill M.J. Timing luteal support in assisted reproductive technology: a systematic review. Fertil. Steril. 2015; 103(4): 939-946.e3. https://dx.doi.org/10.1016/j.fertnstert.2014.12.125.
  20. Dashti S., Eftekhar M. Luteal-phase support in assisted reproductive technology: an ongoing challenge. Int. J. Reprod. BioMed. 2021; 19(9): 761-72. https://dx.doi.org/10.18502/ijrm.v19i9.9708.
  21. Bergh C., Lindenberg S.; Nordic Crinone Study Group. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection. Hum. Reprod. 2012; 27(12): 3467-73. https://dx.doi.org/10.1093/humrep/des341.
  22. Wang Y., He Y., Zhao X., Ji X., Hong Y., Wang Y. et al. Crinone gel for luteal phase support in frozen-thawed embryo transfer cycles: a prospective randomized clinical trial in the Chinese population. PLoS One. 2015; 10(7): e0133027. https://dx.doi.org/10.1371/journal.pone.0133027.
  23. Тапильская Н.И., Гзгзян А.М., Коган И.Ю., Писарев В.В., Меркулов М.Е., Корнеева И.Е. Сравнительные фармакокинетические свойства и оценка безопасности воспроизведенного препарата прогестерона в форме вагинального геля: результаты открытого рандомизированного перекрестного исследования биоэквивалентности. Акушерство и гинекология. 2022; 8: 144-52. [Tapilskaya N.I., Gzgzyan А.М., Kоgan I.Yu., Pisarev V.V., Merkulov М.Е., Korneeva I.E. Pharmacokinetic properties and safety assessment of the generic vaginal gel progesterone preparation: results of an open-label, randomized, crossover bioequivalence study. Obstetrics and Gynecology. 2022; (8): 144-52. (in Russian)]. https://dx.doi.org/10.18565/aig.2022.8.144-152.

Received 20.02.2024

Accepted 18.03.2024

About the Authors

Elena N. Mayasina, PhD, obstetrician-gynecologist, Deputy General Director, Clinical Institute of Reproductive Medicine, 620014, Russia, Yekaterinburg,
Boris Yeltsin str., 3, office 503, +7(919)381-27-44, elena.mayasina@gmail.com, https://orcid.org/0000-0002-3387-819X
Yurii E. Buev, Clinical Institute of Reproductive Medicine (Yekaterinburg), dr.yebuev@mail.ru, https://orcid.org/0009-0001-2539-5796
Roman A. Askerov, Clinical Institute of Reproductive Medicine (Yekaterinburg), roman.askerov@gmail.com, https://orcid.org/0000-0002-0307-4609
Naylya Sh. Yamalyeva, Clinical Institute of Reproductive Medicine (Yekaterinburg), naylya.yamalyeva@icloud.com, https://orcid.org/0009-0008-0581-750X
Ekaterina A. Kichigina, Clinical Institute of Reproductive Medicine (Yekaterinburg), Doc.kichigina@gmail.com, https://orcid.org/0009-0008-4126-5976
Anna S. Kornilova, Clinical Institute of Reproductive Medicine (Yekaterinburg), korn-anna@yandex.ru, https://orcid.org/0009-0007-5278-8273
Daniil F. Salimov, Clinical Institute of Reproductive Medicine (Yekaterinburg), dfsalimov@mail.ru, https://orcid.org/0009-0004-2972-494X
Corresponding author: Elena N. Mayasina, elena.mayasina@gmail.com

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