Regulatory control of gestagens use in Russia in the era of individualized luteal phase support for assisted reproduction cycles

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Approximately 12-18% of couples are infertile, according to WHO for the last 20 or 30 years. The most effective approach in the infertility treatment is assisted reproductive technology (ART). Despite the active development of this area and the constant improvement of the existing protocols, the gap between the pregnancy rate and the live birth rate reaches almost 30%. One of the serious difficulties standing in the way of the achieving a better reproductive outcome is the lag of the regulatory framework from the amount for some aspect’s elaboration, for example, the gestagens use for ART in Russia. The purpose of this review is to accumulate the latest data on the luteal phase support individualization in the post-transfer period based on biomarker — serum progesterone level, to analyze possible ways to overcome insurance and expert risks when using unregulated progesterone doses and dosage regimens, to emphasize the need for continuity in luteal phase support and pregnancy after ART to ensure the increase in the main criterion of ART effectiveness — live birth.

Keywords:

assisted reproductive technologies

progesterone

luteal phase support

normative regulation

individualization

live birth

Authors:

Pestova T.I.

GBUZ «OPTS»

Koloda Yu.A.

OOO «Reproduction Center «Line of Life»;
Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0003-2502-575X

Smirnova A.A.

KDF-Zapad LLC

ORCID: 0000-0003-3035-5921

L’vova A.G.

GMS fertility clinic

ORCID: 0000-0003-0840-1434

Boyarskij K.Yu.

North-Western State Medical University named after I.I. Mechnikov;
Center of Human Reproduction «Genesis»

ORCID: 0000-0002-5324-0863

Denisova Yu.V.

Russian Medical Academy of Continuous Professional Education;
Pletnev City Clinical Hospital

ORCID: 0000-0003-1753-0537

Received:

29.05.2024

Accepted:

30.07.2024

List of references:

Korsak VS, Smirnova AA, Shurygina OV. ART Register of RAHR, 2020. Russian Journal of Human Reproduction. 2022;28(6):12-27. (In Russ.). https://doi.org/10.17116/repro20222806112
Korsak VS, Smirnova AA, Shurygina OV. ART Register of RAHR, 2021. Russian Journal of Human Reproduction. 2023;29(6):25-40. (In Russ.). https://doi.org/10.17116/repro20232906125
Pfister A, Crawford NM, Steiner AZ. Association between diminished ovarian reserve and luteal phase deficiency. Fertility and Sterility. 2019;112(2):378-386. https://doi.org/10.1016/j.fertnstert.2019.03.032
Ku CW, Zhang X, Zhang VR, Allen JC, Tan NS, Østbye T, Tan TC. Gestational age-specific normative values and determinants of serum progesterone through the first trimester of pregnancy. Scientific Reports. 2021;11(1):4161. https://doi.org/10.1038/s41598-021-83805-w
Labarta E, Mariani G, Rodríguez-Varela C, Bosch E. Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles. Fertility and Sterility. 2022;117(1):96-103. https://doi.org/10.1016/j.fertnstert.2021.08.040
Sindrom polikistoznyh yaichnikov. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2021. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/recomend/258_2
European IVF Monitoring consortium (EIM), 1997-2019. Accessed July 20, 2024. https://www.eshre.eu/
Normal’nayaberemennost’. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2020. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/recomend/288
Vykidysh (Samoproizvol’nyi abort). Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2021. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/schema/670?ysclid=lywkf7oj1s206724684
Privychnyi vykidysh. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2021. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/schema/721_1?ysclid=lywm1wm1lk330493280
Istmiko-cervical’naya nedostatochnost’. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2020. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/schema/671_1?ysclid=lywm2rwpol92036117
Prezhdevremennye rody. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2020. Accessed July 20, 2024. (In Russ.). https://cr.minzdrav.gov.ru/schema/331_1?ysclid=lywm3lejlu475406822
Zhenskoe besplodie. Klinicheskie rekomendacii. Odobreno Nauchno-prakticheskim Sovetom Ministerstva zdravoohraneniya Rossijskoj Federacii. 2020. Accessed July 20, 2024. (In Russ.). https://moniiag.ru/wp-content/uploads/2019/07/Klinicheskie-rekomendatsii.-ZHenskoe-besplodie.pdf?ysclid=lywm56dqcm493927775
ESHRE guideline: ovarian stimulation for IVF/ICSI (translated into russian under the editorship of prof. V. Korsak). Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2021;9(2):34-47. (In Russ.). https://doi.org/10.33029/2303-9698-2021-9-2-34-51
Nouola-Martinez N, Halhali A, Barrera D. Steroid hormones and pregnancy. Gynecological Endocrinology. 2019;35(5):376-84. https://doi.org/10.1080/09513590.2018.1564742
van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support in assisted reproduction cycles. The Cochrane Database of Systematic Rewiews. 2015;2015(7):CD009154. https://doi.org/10.1002/14651858
Wu H, Zhang S, Lin X, He J, Wang S, Zhou P. Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis. Reproductive Biology and Endocrinology. 2021;19(1):165. https://doi.org/10.1186/s12958-021-00846-6
O’Brien JM, Defranco EA, Adair CD, Lewis DF, Hall DR, How H, Bsharat M, Creasy GW; Progesterone Vaginal Gel Study Group. Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial. Ultrasound in Obstetrics and Gynecology. 2009;34(6):653-659. https://doi.org/10.1002/uog.7338
Gromova OA, Torshin IYu, Tetruashvili NK, Limanova OA. Systematic analysis of experimental and clinical pharmacology of micronized progesterone preparations. Voprosy ginekologii, akusherstva i perinatologii. 2021;20(4):93-105. (In Russ.). https://doi.org/10.20953/1726-1678-2021-4-93-105
Huppertz B. Traditional and New Routes of Trophoblast Invasion and Their Implications for Pregnancy Diseases. International Journal of Molecular Sciences. 2019;21(1):289. https://doi.org/10.3390/ijms21010289
Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, Bellver J, Cruz F, Marzal A, Celada P, Olmo I, Alamá P, Remohi J, Bosch E. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Human Reproduction. 2021;36(3):683-692. https://doi.org/10.1093/humrep/deaa322
Melo P, Chung Y, Pickering O, Price MJ, Fishel S, Khairy M, Kingsland C, Lowe P, Petsas G, Rajkhowa M, Sephton V, Tozer A, Wood S, Labarta E, Wilcox M, Devall A, Gallos I, Coomarasamy A. Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis. Fertility and Sterility. 2021;116(6):1534-1556. https://doi.org/10.1016/j.fertnstert.2021.07.002
Progesterone Injection in Sesame Oil – FDA instruction for use. Accessed July 20, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017362s104lbl.pdf
Progesteron — Dal’himfarm — instrukciya po primeneniyu. Accessed July 20, 2024. (In Russ.). https://medi.ru/instrukciya/progesteron_22589/
Massarotti C, Ammar OF, Liperis G, Uraji J, Drakopoulos P, Labarta E, Maheshwari A, Cheong Y, Makieva S, Fraire-Zamora JJ. Progesterone in HRT-FET cycles: a game of hide and seek. Human Reproduction. 2023;38(10):2039-2043. https://doi.org/10.1093/humrep/dead153
Li TC, Aplin JD, Warren A, Graham RA, Dockery P, Cooke ID. Endometrial responses to three different progestins in artificial cycles: a prospective, crossover study. Fertility and Sterility. 1994;62(1):191-193. https://doi.org/10.1016/s0015-0282(16)56840-x
Barbosa MW, Silva LR, Navarro PA, Ferriani RA, Nastri CO, Martins WP. Dydrogesterone vs progesterone for luteal‐phase support: systematic review and meta‐analysis of randomized controlled trials. Ultrasound in Obstetrics and Gynecology. 2016;48(2):161-170. https://doi.org/10.1002/uog.15814
Cicinelli E, de Ziegler D, Bulletti C, Matteo MG, Schonauer LM, Galantino P. Direct transport of progesterone from vagina to uterus. Obstetrics and Gynecology. 2000;95(3):403-406. https://doi.org/10.1016/s0029-7844(99)00542-6
Baker VL, Jones CA, Doody K, Foulk R, Yee B, Adamson GD, Cometti B, DeVane G, Hubert G, Trevisan S, Hoehler F, Jones C, Soules M. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization. Human Reproduction. 2014;29(10):2212-2220. https://doi.org/10.1093/humrep/deu194
Turgut EN, Boynukalın FK, Gültomruk M, Yarkıner Z, Bahçeci M. Comparison of intramuscular versus subcutaneous aqueous progesterone for luteal phase support in artificially prepared frozen embryo transfer cycles. Turkish Journal of Obstetrics and Gynecology. 2020;17(4):240. https://doi.org/10.4274/tjod.galenos.2020.01460
Doblinger J, Cometti B, Trevisan S, Griesinger G. Subcutaneous progesterone is effective and safe for luteal phase support in IVF: an individual patient data meta-analysis of the phase III trials. PLoS One. 2016;11(3):e0151388. https://doi.org/10.1371/journal.pone.0151388
Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Human Reproduction. 2017;32(12):2437-2442. https://doi.org/10.1093/humrep/dex316
Boyarskij KYu, Brailko OV, Bykovskaya OS, Gzgzyan AM, Denisova YuV, Zorina IV, et al. Luteal phase support in ART programs the necessity of optimization and the importance of personalization. Russian Journal of Human Reproduction. 2022;28(3):66-77. (In Russ.).
Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertility and Sterility. 2015;103(4):e27-32. https://doi.org/10.1016/j.fertnstert.2014.12.128
de Ziegler D, Sator M, Binelli D, Leuratti C, Cometti B, Bourgain C, Fu YS, Garhöfer G. A randomized trial comparing the endometrial effects of daily subcutaneous administration of 25 mg and 50 mg progesterone in aqueous preparation. Fertility and Sterility. 2013;100(3):860-866. https://doi.org/10.1016/j.fertnstert.2013.05.029
du Boulet B, Ranisavljevic N, Mollevi C, Bringer-Deutsch S, Brouillet S, Anahory T. Individualized luteal phase support based on serum progesterone levels in frozen-thawed embryo transfer cycles maximizes reproductive outcomes in a cohort undergoing preimplantation genetic testing. Frontiers in Endocrinology. 2022;13:1051857. https://doi.org/10.3389/fendo.2022.1051857
Venturella R, Vaiarelli A, Buffo L, D’alessandro P, Colamaria S, Pedri S, Di Carlo C, Alviggi E, Forte M, Faustini F, Zullo F, Rienzi L, Ubaldi FM. Progesterone for preparation of the endometrium for frozen-thawed blastocyst transfer in vitro fertilization cycles: a prospective study on patients’ opinions on a new subcutaneous formulation. Gynecological Endocrinology. 2018;34(9):766-771. https://doi.org/10.1080/09513590.2018.1451508
WHO. Anatomical Therapeutic Chemical. G03D/Progestogens. Accessed July 20, 2024. https://www.classinform.ru
Perechen’ zhiznenno neobkhodimykh i vazhneyshikh lekarstvennykh preparatov dlya meditsinskogo primeneniya na 2022 god. Rasporyazhenie Pravitelstva Rossijskoj Federacii ot 12.10.2019 N 2406-r s izmeneniyami, vnesennymi rasporyazheniem Pravitelstva Rossijskoj Federacii ot 24.12.2022 vstupivshimi v silu s 01.01.2023. Accessed July 20, 2024. (In Russ.). https://government.ru/docs/all/124156/
Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii ot 19.03.2021 № 231n (red. ot 01.07.2021) «Ob utverzhdenii Poryadka provedeniya kontrolya obemov, srokov, kachestva i usloviy predostavleniya meditsinskoy pomoshchi po obyazatelnomu meditsinskomu strakhovaniyu zastrakhovannym litsam, a takzhe ee finansovogo obespecheniya» (Zaregistrirovano v Minyuste Rossii 13.05.2021 № 63410). Accessed July 20, 2024. (In Russ.). https://normativ.kontur.ru/document?moduleId=1&documentId=468321&ysclid=lywnjrxm4l407017771
Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii № 803not 31.07.2020 «O Poryadke ispolzovaniya vspomogatelnykh reproduktivnykh tekhnologiy, protivopokazaniyakh i ogranicheniyakh k ikh primeneniyu». Accessed July 20, 2024. (In Russ.). https://www.garant.ru/products/ipo/prime/doc/74676088/
Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii № 556n ot 30.11.2012 «Ob utverzhdenii Standarta meditsinskoy pomoshchi pri besplodii s ispolzovaniem vspomogatelnykh reproduktivnykh tekhnologiy» (s izmeneniyami ot 01.02.2018). Accessed July 20, 2024. (In Russ.). https://minzdrav.gov.ru/documents/8491-prikaz
Prikaz Ministerstva zdravoohraneniya i social’nogo razvitiya Rossijskoj Federacii ot 05.05.2012 g. № 502n «O Poryadke sozdaniya i deyatelnosti vrachebnoy komissii meditsinskoy organizatsii». Accessed July 20, 2024. (In Russ.). https://rg.ru/documents/2012/06/22/komissia-dok.html?ysclid=lywnru4j4b227537403
Practice Committees of the American Society for Reproductive Medicine and the Society for Reproductive Endocrinology and Infertility. Diagnosis and treatment of luteal phase deficiency: a committee opinion. Fertility and Sterility. 2021;115(6):1416-1423. https://doi.org/10.1016/j.fertnstert.2021
Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reproductive BioMedicine Online. 2018;36(6):630-645. https://doi.org/10.1016/j.rbmo.2018.02.001
Shoham G, Leong M, Weissman A. 10-year follow-up on the practice of luteal phase support using worldwide web-based surveys. Reproductive Biology and Endocrinology. 2021;19(1):15. https://doi.org/10.1186/s12958-021-00696-2
Sator M, Radicioni M, Cometti B, Loprete L, Leuratti C, Schmidl D, Garhöfer G. Pharmacokinetic and safety profile of a novel progesterone aqueous formulation administration by the s.c. route. Gynecological Endocrinology. 2013;29(3):205-208. https://doi.org/10.3109/09513590.2012.736560
Ramos NN, Pirtea P, Benammar A, Ziegler D, Jolly E, Frydman R, Poulain M, Ayoubi JM. Is there a link between plasma progesterone 1-2 days before frozen embryo transfers (FET) and ART outcomes in frozen blastocyst transfers? Gynecological Endocrinology. 2021;37(7):614-617. https://doi.org/10.1080/09513590.2020.1825669
Ranisavljevic N, Huberlant S, Montagut M, Alonzo PM, Darné B, Languille S, Anahory T, Cédrin-Durnerin I. Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses. Frontiers in Endocrinology. 2022;13:892753. https://doi.org/10.3389/fendo.2022.892753
Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Humaidan P, Yarali H. Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review. Frontiers in Endocrinology. 2021;12:688237. https://doi.org/10.3389/fendo.2021.688237
Bjuresten K, Landgren BM, Hovatta O, Stavreus-Evers A. Luteal phase progesterone increases live birth rate after frozen embryo transfer. Fertility and Sterility. 2011;95(2):534-537. https://doi.org/10.1016/j.fertnstert.2010.05.019

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