Review of the results of clinical studies of follitropin delta in ovarian stimulation protocols. The first experience of its use in Russia
- Authors: Kalugina A.S.1,2, Boyarsky K.Y.3,4, Makolkin A.A.5, Zvereva I.O.6,7, Voznesenskaya J.V.8, Kholodov D.V7
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Affiliations:
- Academician I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia
- Scanfert Clinic
- I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
- Genesis Reproduction Center
- Delta Fertility Clinic
- M.V. Lomonosov Moscow State University of Fine Chemical Technologies
- Fomin Clinic
- European Medical Center
- Issue: No 11 (2021)
- Pages: 246-264
- Section: Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/249574
- DOI: https://doi.org/10.18565/aig.2021.11.246-264
- ID: 249574
Cite item
Open Access
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Abstract
The paper presents the results of the clinical studies ESTHER-1, ESTHER-2, MARCS, STORK, and GRAPE, which have evaluated the efficacy of follitropin delta for ovarian stimulation (OS) in infertility programs with assisted reproductive technologies (ART). The ESTHER-1 and ESTHER-2 studies have been conducted on 1,326 women from several countries around the world. The studies have evaluated the effectiveness of individual calculation of the dosage of the OS drug, as well as its safety profile, especially in terms of the development of ovarian hyperstimulation syndrome (OHSS), one of the most common and serious complications of controlled OS. The ESTHER-2 study has assessed the safety profile of the second and third OS cycles. The STORK and GRAPE studies of 347 patients from Japan and 1009 women from several Asian countries have evaluated the efficacy of follitropin delta, taking into account the ethnic characteristics of the patients. The MARCS study enrolling 110 patients has analyzed the efficacy of a mixed protocol of follitropin delta and a highly purified urine-derived menopausal gonadotropin. The conducted clinical studies have shown that individual calculation of the dosage of follitropin delta offers benefits in a significant reduction in the risks of OHSS with comparable or better indicators for the number of oocytes collected, in the frequency of pregnancy, etc., which also allow the use of smaller total follitropin delta doses than those in the standard regimens. Following a review of the studies examples of clinical experience with follitropin delta in mono- and mixed protocols for women with low, normal, and high ovarian reserves are given. Conclusion: The gained experience with follitropin delta confirms its eff icacy in both mono- and mixed protocols in patients with low, normal and high ovarian reserves. Follitropin delta helps achieve a predictable ovarian response while minimizing the risk of OHSS, including patients with endocrine factor infertility (including polycystic ovary syndrome).
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About the authors
Alla S. Kalugina
Academician I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia; Scanfert Clinic
Email: alla19021962@gmail.com
reproductologist, Dr. Med. Sci., Professor of the Department of Obstetrics, Gynecology and Neonatology
Konstantin Yu. Boyarsky
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia; Genesis Reproduction Center
Email: konstantinboyarsky@icloud.com
reproductologist, Ph.D., Associate Professor of the S.N. Davydov Department of Obstetrics and Gynecology, Pediatric Faculty
Alexander A. Makolkin
Delta Fertility Clinicreproductologist
Irina O. Zvereva
M.V. Lomonosov Moscow State University of Fine Chemical Technologies; Fomin Clinic
Email: zvereva.sochi2014@gmail.com
embryologist, Ph.D., Associate Professor of the Department of Analytical Chemistry named after IP. Alimarin, Department of Fundamental and Engineering Chemistry
Julia V. Voznesenskaya
European Medical Center
Email: klimka7@yahoo.com
reproductologist, Head of the EMC Medical School of Reproduction
D. V Kholodov
Fomin Clinic
Email: dmitrykholodov@gmail.com
References
- World Health Organization. Infertility. Available at: https://www.who.int/news-room/fact-sheets/detail/infertility
- Гусаров Д.А., Государев А.И., Гусарова В.Д., Бырихина Д.В., Ижаева Ф.М. Создание промышленной технологии биосинтеза фолликулостимулирующего гормона в культуре клеток СНО. Разработка и регистрация лекарственных средств. 2016; 2: 80-4
- Andersen A.N., Nelson S.M., Fauser B.C.J.M., Garcia-Velasco J.A., Klein B.M., Arce J.-C.; ESTHER-1 study group. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil. Steril. 2017; 107(2): 387-396.e4. https://dx.doi.org/10.1016/j.fertnstert.2016.10.033
- Fernandez-Sanchez M, Visnova H., Yuzpe A., Klein B.M., Mannaerts B., Arce J.-C.; ESTHER-1 and ESTHER-2 Study Group. Individualization of the starting dose of follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles. Reprod. Biomed. Online. 2019; 38(4): 528-37. https://dx.doi.org/10.1016/j.rbmo.2018.12.032
- Bosch E., Havelock J., Martin F.S., Rasmussen B.B., Klein B.M., Mannaerts B. et al.; ESTHER-2 Study Group. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial. Reprod. Biomed. Online. 2019; 38(2): 195-205. https://dx.doi.org/10.1016/j.rbmo.2018.10.012
- Bissonnette F., Masip J.M., Kadoch I.-J., Librach C., Sampalis J., Yuzpe A. Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin. Fertil. Steril. 2021; 115(4): 991-1000. https://dx.doi.org/10.1016/j.fertnstert.2020.09.158
- Bleil M.E., Gregorich S.E., Adler N.E., Sternfeld B., Rosen M.P., Cedars M.I. Race/ethnic disparities in reproductive age: an examination of ovarian reserve estimates across four race/ethnic groups of healthy, regularly cycling women. Fertil. Steril. 2014; 101(1): 199-207. https://dx.doi.org/10.1016/j.fertnstert.2013.09.015
- Nelson S.M., Aijun S., Ling Q., Tengda X., Wei X., Yan D. et al. Ethnic discordance in serum anti-Mullerian hormone in healthy women: a population study from China and Europe. Reprod. Biomed. Online. 2020; 40(3): 461-7. https://dx.doi.org/10.1016/j.rbmo.2019.11.013
- Ishihara O., Klein B.M., Arce J.-C.; Japanese Follitropin Delta Phase 2 Trial Group. Randomized, assessor-blind, antimullerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta. Fertil. Steril. 2021; 115(6): 1478-86. https://dx.doi.org/10.1016/j.fertnstert.2020.10.059.
- Ishihara O., Arce J.-C.; Japanese Follitropin Delta Phase 3 Trial (STORK) Group. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. Reprod. Biomed. Online. 2021; 42(5): 909-18. https://dx.doi.org/10.1016/j.rbmo.2021.01.023.
- Qiao J., Zhang Y., Liang X., Ho T., Huang H.-Y., Kim S.-H. et al. A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients. Hum. Reprod. 2021; 36(9): 2452-62. https://dx.doi.org/10.1093/humrep/deab155.
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