Outcomes of IVF programs using the short protocol with recombinant follitropin alfa preparations
DOI:
https://doi.org/10.37800/RM.3.2026.832Keywords:
controlled ovarian stimulation (COS), in vitro fertilization (IVF), recombinant follitropin alfa, Foligraf, Gonal-FAbstract
Relevance: Controlled ovarian stimulation (COS) is a key stage of in vitro fertilization (IVF) and significantly affects reproductive treatment outcomes. In clinical practice in the Republic of Kazakhstan, recombinant follitropin alfa preparations include Gonal-F (Merck Serono S.p.A., Rome, Italy), used for approximately 30 years, and Foligraf (Bharat Serums and Vaccines Limited, Mumbai, India), used for 5 years. Evaluation of the clinical efficacy, safety profile, and embryological outcomes associated with Foligraf use is of practical clinical interest.
The study aimed to evaluate the efficacy and safety of Foligraf for controlled ovarian stimulation in IVF programs
Materials and Methods: We conducted a retrospective, non-randomized, comparative cohort study to evaluate outcomes from completed IVF cycles with embryo transfer performed between 2023 and 2025. The study included patients under 35 years of age who underwent treatment using a short protocol with a gonadotropin-releasing hormone (GnRH) antagonist. Following the application of exclusion criteria (concomitant use of menotropins, GnRH agonist trigger, AMH levels outside the range of 1–3.5 ng/mL, advanced reproductive age, male factor infertility, multifollicular ovaries, and ICSI), two groups were formed: the study group, comprising 67 patients who received Foligraf, and the control group, comprising 88 patients who received Gonal-F. Final oocyte maturation was induced using recombinant human chorionic gonadotropin (rhCG), while fertilization was performed using conventional IVF.
Results: No statistically significant differences were observed between the groups in the number of oocytes retrieved, the number of mature MII oocytes, the number of two-pronuclear (2PN) zygotes, the blastulation rate, the number of good-quality embryos according to the Gardner classification, clinical pregnancy rate, or live birth rate (p > 0.05). The reproductive loss rate was 17.2% in the Foligraf group and 18.4% in the Gonal-F group (p = 1.0). No statistically significant differences were identified between the groups.
Conclusion: The results obtained are consistent with data from previously published studies evaluating the efficacy of Folligraf and Gonal-F. Further comparative studies are needed to evaluate the clinical efficacy and safety of Folligraf in different patient populations and with different treatment protocols.
References
1. Локшин В.Н., Сулейменова М.Д., Ахметова А.А., Арипова Р.С., Байкошкарова С.Б., Чалова Л.Р., Диамантиди Н.Н., Джусубалиева Т.М., Имтосими Д.Г., Карабалин А.А., Ким В.В., Крылдаков А.А., Лапина Е.В., Магарманова С.М., Макишева А.Т., Мухамедьяров Д.А., Нигматова Н.П., Нигметова К.Т., Отарбаев М.К., Покотило Л.И., Тарарака Н.С., Тарарака С.С., Толеубаева К.Т., Яхьярова М.П., Ермеков М.Ш., Есенаманова С.М. Вспомогательные репродуктивные технологии в Казахстане (данные Национального регистра, 2021 г.). Репрод Мед (Центр Азия). 2025;1:10-19.
Lokshin VN, Suleimenova MD, Akhmetova AA, Aripova RS, Baikoshkarova SB, Chalova LR, Diamantidi NN, Dzhusubalieva TM, Imtosimi DG, Karabalin AA, Kim VV, Kryldakov AA, Lapina EV, Magarmanova SM, Makisheva AT, Mukhamedyarov DA, Nigmatova NP, Nigmetova KT, Otarbayev MK, Pokotilo LI, Tararaka NS, Tararaka SS, Toleubayeva KT, Yakhyarova MP, Yermekov MSh, Yesenamanova SM. Assisted reproductive technologies in Kazakhstan: data from the National Register, 2021. Reprod Med (Centr Asia). 2025;1:10-19. Russian.
https://doi.org/10.37800/RM.1.2025.443
2. The European IVF Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE), Smeenk J, Wyns C, De Geyter Ch, Kupka MS, Bergh C, Cuevas Saiz I, De Neubourg D, Rezabek K, Tandler-Schneider A, Rugescu I, Goossens V. ART in Europe, 2020: results generated from European registries by ESHRE. Hum Reprod. 2025;40(11):2038-2055.
https://doi.org/10.1093/humrep/deaf179
3. Сыркашева А.Г., Агаршева М.В., Андреева М.Г., Долгушина Н.В., Калинина Е.А., Яроцкая Е.Л. Современные представления о дифференцированном подходе к выбору протокола стимуляции суперовуляции в циклах ЭКО. Акушерство и гинекология. 2016;(5):38-43.
Syrkasheva AG, Agarsheva MV, Andreeva MG, Dolgushina NV, Kalinina EA, Yarotskaya EL. Current concepts of a differentiated approach to choosing a superovulation stimulation protocol in IVF cycles. Obstetrics and Gynecology. 2016;(5):38-43. Russian.
https://doi.org/10.18565/aig.2016.5.38-43
4. ESHRE Guideline Group on Ovarian Stimulation, Ata B, Bosch E, Broer S, Griesinger G, Grynberg M, Kolibianakis E, Kunicki M, La Marca A, Lainas G, Le Clef N, Massin N, Polyzos NP, Sunkara SK, Timeva T, Töyli M, Urbancsek J, Broekmans F. ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025. Hum Reprod. 2026;41(4):498-514.
https://doi.org/10.1093/humrep/deag018
5. Howles CM. Advances in ART pharmacology: drug delivery systems and the pipeline. In: Domar AD, Sakkas D, Toth TL, editors. Patient-centered assisted reproduction: how to integrate exceptional care with cutting-edge technology. Cambridge: Cambridge University Press; 2020. p. 23-38.
https://doi.org/10.1017/9781108859486.004
6. Локшин В.Н., Абшекенова А.Т., Карибаева Ш.К., Рыбина А.Н., Аскар Е., Валиев Р.К. Оценка эффективности стимуляции суперовуляции прогестинами в программах ЭКО/ИКСИ у доноров ооцитов: ретроспективное обсервационное нерандомизированное исследование. Репрод Мед (Центр Азия). 2026;2:163-170.
Lokshin VN, Abshekenova AT, Karibayeva ShK, Rybina AN, Askar E, Valiyev RK. Evaluation of the effectiveness of progestin-primed ovarian stimulation in IVF/ICSI programs in oocyte donors: a retrospective observational non-randomized study. Reprod Med (Centr Asia). 2026;2:163-170. Russian.
https://doi.org/10.37800/RM.2.2026.730
7. Экспертный совет по возможностям импортозамещения препаратов фоллитропина альфа в циклах ЭКО. Акушерство, гинекология и репродукция. 2021;15(4):470-492.
Advisory Board on potential import substitution of follitropin alfa preparations in IVF cycles. Obstetrics, Gynecology and Reproduction. 2021;15(4):470-492. Russian.
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.246
8. Перминова С.Г., Назаренко Т.А., Корнеева И.Е., Башмакова Н.В., Митюрина Е.В., Алимова О.А., Белова И.С., Ершов А.В., Храмцова А.Ю., Джалилова Э.Р. Результаты сравнительного исследования эквивалентности биоаналогичного препарата фоллитропина альфа (раствор для подкожного введения) и оригинального препарата фоллитропина альфа (лиофилизат для приготовления раствора для подкожного введения) у женщин с различным ответом на овариальную стимуляцию в программе экстракорпорального оплодотворения: резюме результатов клинического исследования IV фазы. Акушерство и гинекология. 2022;(10):138-149.
Perminova SG, Nazarenko TA, Korneeva IE, Bashmakova NV, Mityurina EV, Alimova OA, Belova IS, Ershov AV, Khramtsova AYu, Dzhalilova ER. Results of a comparative equivalence study of a biosimilar follitropin alfa preparation, solution for subcutaneous administration, and the original follitropin alfa preparation, lyophilizate for solution for subcutaneous administration, in women with different ovarian responses in an in vitro fertilization program: summary of the results of a phase IV clinical trial. Obstetrics and Gynecology. 2022;(10):138-149. Russian.
https://doi.org/10.18565/aig.2022.10.138-149
9. Shah P, Bhat V, Bakshi R, Karakhalis LY, Vinod K, Khanna G, et al. A Phase 3 Noninferiority Study Comparing the Efficacy, Immunogenicity, and Safety of Foligraf®: A Biosimilar Recombinant Human Follicle-stimulating Hormone and Gonal-f® (Prefilled Pen) in Subjects Undergoing Controlled Ovarian Stimulation for Assisted Reproductive Technology. Int J Infertil Fetal Med. 2025;16(3):164–172.
https://doi.org/10.5005/jp-journals-10016-1395
10. Hu L, Zhang S, Quan S, Lv J, Qian W, Huang Y, Lu W, Sun Y. Efficacy and safety of recombinant human follicle-stimulating hormone in patients undergoing in vitro fertilization-embryo transfer. Aging (Albany NY). 2020;12(6):4918-4930.
https://doi.org/10.18632/aging.102919
11. Rashidi BH, Sayyari K, Heshmat R, Amanpour S, Tehraninejad ES, Masoumi M, Rezaei F. Comparing a biosimilar follitropin alfa (Cinnal-f®) with Gonal-f® in women undergoing ovarian stimulation: an RCT. Int J Reprod Biomed. 2021;19(11):1015-1024.
https://doi.org/10.18502/ijrm.v19i11.9917
12. Гонал-Ф®. Инструкция по медицинскому применению лекарственного средства [Электронный ресурс]. Утверждена приказом Председателя РГУ «Комитет контроля качества и безопасности товаров и услуг» МЗ РК от 31 декабря 2020 г. № 035216. [дата обращения: 29.08.2026]. Адрес доступа:
Gonal-F®. Instructions for medical use of the medicinal product [Internet]. Approved by Order No. 035216 of the Chairman of the Committee for Quality Control and Safety of Goods and Services of the Ministry of Health of the Republic of Kazakhstan, December 31, 2020. [cited 2026 Aug 29]. Russian. Available from:
https://prg.kz/document/?doc_id=37525824
13. ФОЛИГРАФ (фоллитропин альфа): инструкция по медицинскому применению лекарственного препарата [Электронный ресурс]. Алматы: MedElement; 2021 [дата обращения: 29.08.2026]. Адрес доступа:
Foligraf (follitropin alfa): instructions for medical use of the medicinal product [Internet]. Almaty: MedElement; 2021 [cited 2026 Aug 29]. Russian. Available from:
https://drugs.medelement.com/drug/фолиграф-150ме инструкция/984494981695215393?instruction_lang=RU
14. Министерство здравоохранения Республики Казахстан. Об утверждении правил и условий проведения вспомогательных репродуктивных методов и технологий: приказ Министра здравоохранения Республики Казахстан от 15 декабря 2020 года № ҚР ДСМ-272/2020, в редакции от 15 февраля 2023 года. Зарегистрирован в Министерстве юстиции Республики Казахстан 20 декабря 2020 года № 21816 [Интернет]. Астана; 2020 [дата обращения: 24.09.2026].
Ministry of Healthcare of the Republic of Kazakhstan. On approval of the rules and conditions for conducting assisted reproductive methods and technologies: Order of the Minister of Healthcare of the Republic of Kazakhstan No. ҚР ДСМ-272/2020 dated December 15, 2020, as amended on February 15, 2023. Registered with the Ministry of Justice of the Republic of Kazakhstan on December 20, 2020, No. 21816 [Internet]. Astana; 2020 [cited 2026 Sep 24]. Russian.
https://zakon.uchet.kz/rus/docs/V2000021816
15. Salame AA, Zhaffal MJ, Peramo B. Early pregnancy loss in IVF: a literature review. Middle East Fertil Soc J. 2024;29:30.
https://doi.org/10.1186/s43043-024-00191-9
16. Konishi H, Matsumoto H, Fujiwara S, Kitayama R, Kadogami D, Morimoto N, et al. Association between miscarriage rates in modified natural ovulation cycles and hormone replacement cycles during frozen-thawed embryo transfer in three IVF JAPAN GROUP fertility clinics: a retrospective analysis. Middle East Fertility Society Journal [Internet]. 2026 Mar 7 [cited 2026 Sept 23];31(1). Available from:
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 С.М. Есенаманова, Г.К. Бекбосинова, Б.К. Джакупова , К.З. Утянова
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The articles published in this Journal are licensed under the CC BY-NC-ND 4.0 (Creative Commons Attribution – Non-Commercial – No Derivatives 4.0 International) license, which provides for their non-commercial use only. Under this license, users have the right to copy and distribute the material in copyright but are not permitted to modify or use it for commercial purposes. Full details on the licensing are available at https://creativecommons.org/licenses/by-nc-nd/4.0/.
