An observational study «FOLLITROPIN» comparing the efficacy of follitropin alpha biosimilar: the real-world data
D. P. Kamilova,
M. M. Ovchinnikova,
E. Sh. Ablyaeva,
M. M. Leviashvili,
N. S. Stuleva,
E. V. Broitman,
M. A. Ganikhina,
E. N. Mayasina,
L. F. Iskhakova,
K. Yu. Boyarskiy,
E. N. Ovsyannikova,
Z. B. Barakhoeva,
S. V. Nikitin,
I. A. Bendusov,
Yu. A. Fetisova,
M. A. Yudina,
E. S. Tararashkina,
D. T. Khetagurova,
D. V. Blinov,
M. A. Polzikov https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.212
Abstract
Introduction. The efficacy and safety of biosimilar follitropin alpha have been demonstrated in randomized blinded prospective clinical trials of phases I and III. Unfortunately, there is a gap between the clinical trials and real clinical practice data. The real-world patient data helps to create an evidence-based background for successful implementation of medicine at everyday practice in a nonselected population.
Aim: to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.
Materials and Methods. A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.
Results. The overall clinical efficacy of ovarian stimulation cycles (N = 5484) was: oocytes retrieved - 9.5 ± 7.2, mature (MII) - 6.8 ± 6.6, fertilized (2PN) - 6.1 ± 5.8, clinical pregnancy per ET (PR) - 38.4 %. Mixed gonadotropin protocols (N = 2625) vs. monotherapy with Primapur® (N = 2859): oocytes retrieved - 8.6 ± 6.8 vs. 10.3 ± 7.4 (p < 0.001), mature (MII) - 6.7 ± 6.2 vs. 7.7 ± 6.9 (p < 0.001), fertilized (2PN) - 5.8 ± 5.2 vs. 7.2 ± 6.2 (p < 0.001). There were statistically significant differences between oocyte yields in mixed vs. monotherapy protocols due to subgroup differences, including age, body mass index (BMI) and IVF/ICSI attempts. No statistically significant differences were found for PR: 39.3 % vs. 37.6 % (p = 0.314). Monotherapy protocols with GnRH antagonist OS (N = 2183) vs. GnRH agonist (N = 676) revealed: oocytes retrieved - 10.5 ± 7.5 vs. 9.6 ± 7.0 (p = 0.032), mature (MII) - 7.6 ± 6.9 vs. 6.7 ± 5.7 (p < 0.001), fertilized (2PN) - 7.3 ± 6.3 vs. 5.7 ± 5.0 (p < 0.001). There were statistically significant differences between BMI and IVF/ICSI attempts. No statistically significant differences were found for PR: 37.9 % vs. 35.9 % (p = 0.482). All medicines were well tolerated and no serious adverse reactions were reported.
Conclusion. This was the largest retrospective observational study conducted in the field of fertility in Russia and involved 5484 ovarian stimulation protocols at 35 IVF clinics. The obtained results demonstrated similar clinical efficacy for follitropin alpha biosimilar Primapur® in different OS protocols in real clinical practice.
About the Authors
D. P. Kamilova
GC «Mother and Child»
Russian Federation
Russian Federation
Dilorom P. Kamilova - MD, PhD, Chief Physician, Clinic «Mother and Child» Kuntsevo, Chief IVF Specialist of MD Medical Group.
Moscow.
M. M. Ovchinnikova
GC «Mother and Child»
Russian Federation
Russian Federation
Maria M. Ovchinnikova - MD, Reproductologist, Head of the IVF Department, Lapino Clinical Hospital, MD Medical Group.
Moscow Region.
E. Sh. Ablyaeva
GC «Mother and Child»
Russian Federation
Russian Federation
Elmira Sh. Ablyaeva - MD, PhD, Head of the Department of Reproductology, Clinic «Mother and Child» Khodynskoe Pole, MD Medical Group.
Moscow.
M. M. Leviashvili
GC «Mother and Child»
Russian Federation
Russian Federation
Mziya M. Leviashvili - MD, PhD, Reproductologist, Clinic «Mother and Child» Khodynskoe Pole, MD Medical Group.
Moscow.
N. S. Stuleva
Sechenov University; Center of Reproductive Medicine and Genetics «Nova Clinic»
Russian Federation
Russian Federation
Nadezhda S. Stuleva - MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University; Obstetrician-Gynecologist, Center of Reproductive Medicine and Genetics «Nova Clinic».
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; 20 Lobachevsky Str., Moscow 119415.
E. V. Broitman
GC «Mother and Child»
Russian Federation
Russian Federation
Evgeniya V. Broitman - MD, Head of the ART Department, Clinical Hospital «Avicenna», MD Medical Group.
Novosibirsk.
M. A. Ganikhina
GC «Mother and Child»
Russian Federation
Russian Federation
Maria A. Ganikhina - MD, Reproductologist, Head of the IVF Department, Clinical Hospital «Mother and Child», MD Medical Group.
Tyumen.
E. N. Mayasina
Clinical Institute of Reproductive Medicine
Russian Federation
Russian Federation
Elena N. Mayasina - MD, PhD, Vice Director General for Clinical Care, Reproductologist, Clinical Institute of Reproductive Medicine.
Ekaterinburg.
L. F. Iskhakova
GC «Mother and Child»
Russian Federation
Russian Federation
Liliya F. Iskhakova - MD, Reproductologist, Clinical Hospital «Mother and Child», MD Medical Group.
Ufa.
K. Yu. Boyarskiy
«GENESIS» Reproduction Centre; Mechnikov North-Western State Medical University, Health Ministry of Russian Federation
Russian Federation
Russian Federation
Konstantin Yu. Boyarskiy - MD, PhD, Head of the Department of Reproduction and Family Planning, «Genesis» Reproduction Centre; Associate Professor, Department of Obstetrics and Gynecology, Davydov Pediatric Faculty, Mechnikov North-Western State Medical University.
64 Kirochnaya Str., Saint Petersburg 191015; 41 Kirochnaya Str., Saint Petersburg 191015.
E. N. Ovsyannikova
GC «Mother and Child»
Russian Federation
Russian Federation
Elena N. Ovsyannikova - MD, Reproductologist, Clinical Hospital «Mother and Child», MD Medical Group.
Samara.
Z. B. Barakhoeva
«AltraVita» Human Reproduction Clinic
Russian Federation
Russian Federation
Zarema B. Barakoeva - MD, PhD, Reproductologist, «AltraVita» Human Reproduction Clinic.
Moscow.
S. V. Nikitin
GC «Mother and Child»
Russian Federation
Russian Federation
Sergey V. Nikitin - MD, PhD, Head of the ART Department, Clinic «Mother and Child», MD Medical Group.
Saint Petersburg.
I. A. Bendusov
GC «Mother and Child»
Russian Federation
Russian Federation
Ivan A. Bendusov - MD, Head of the ART Department, Clinic «Mother and Child» South-West, MD Medical Group.
Moscow.
Yu. A. Fetisova
GC «Mother and Child»
Russian Federation
Russian Federation
Yulia A. Fetisova - MD, Reproductologist, IVF Department, Clinical Hospital (Perinatal Center on Sevastopolskiy), MD Medical Group.
Moscow.
M. A. Yudina
GC «Mother and Child»
Russian Federation
Russian Federation
Marina A. Yudina - MD, PhD, Obstetrician-Gynecologist, Clinic «Mother and Child», MD Medical Group.
Nizhny Novgorod.
E. S. Tararashkina
GC «Mother and Child»
Russian Federation
Russian Federation
Elena S. Tararashkina - MD, Reproductologist, IVF Department, Clinical Hospital (Perinatal Center on Sevastopolskiy), MD Medical Group.
Moscow.
D. T. Khetagurova
Pirogov Russian National Research Medical University, Health Ministry of Russian Federation
Russian Federation
Russian Federation
Diana T. Khetagurova - MD, Postgraduate Student, Pirogov Russian National Research Medical University.
Moscow.
D. V. Blinov
MD Medical Group; Institute for Preventive and Social Medicine
Russian Federation
Russian Federation
Dmitry V. Blinov - MD, PhD, MBA, Head of Medical and Scientific Affairs, Institute for Preventive and Social Medicine; Neurologist, Lapino Clinical Hospital, MD Medical Group.
Moscow Region; 4—10 Sadovaya-Triumfalnaya Str., Moscow 127006.
Scopus Author ID: 6701744871
Researcher ID: E-8906-2017
RSCI: 9779-8290
M. A. Polzikov
IVFarma LLC
Russian Federation
Russian Federation
Mikhail A. Polzikov - PhD (Chemistry), Director General, IVFarma LLC.
Moscow.
Scopus Author ID: 10139451800
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Review
Supporting agencies: We are grateful to thank the reproductologists who participated in this study aimed to investigate the efficacy of follitropin alpha biosimilar every day clinical practice: Avetyan E.S., Milimbaeva L.R., Railean A.L., Kazantsev V.A., Pavlenko I.I., Mazura A.A., Palamarchuk A.N., Ketiladze T.M., Sinitsyna E. V., Khomova A.A., Feoktistov A.A., Safonova A.D., Pilipenko A.A., Gukasyan S.N., Sakhabieva M.A., Belova A.E., RachenkE.Yu., Khovrina E.A., Lagutina M.V., Sterlikova N.A., Arevanyuk K.I., Kasyanova G.V., Kumaitova O.N., Osina E.A., Zorina I.V., Vovk L A.A., Marilova N.A., Kim N.A., Burlakova O.A., Kolesnikova Yu.V., Burnaeva Yu.A., Andreeva M.N., Baikova O.N., Vanyan R.E., Kalinina I.M., Yakunina N.A., Yanochkina T.G., Borets M.V. and other specialists; Ushakova T.I. help in statistical data analysis.
For citations:
Kamilova D.P., Ovchinnikova M.M., Ablyaeva E.S., Leviashvili M.M., Stuleva N.S., Broitman E.V., Ganikhina M.A., Mayasina E.N., Iskhakova L.F., Boyarskiy K.Yu., Ovsyannikova E.N., Barakhoeva Z.B., Nikitin S.V., Bendusov I.A., Fetisova Yu.A., Yudina M.A., Tararashkina E.S., Khetagurova D.T., Blinov D.V., Polzikov M.A. An observational study «FOLLITROPIN» comparing the efficacy of follitropin alpha biosimilar: the real-world data. Obstetrics, Gynecology and Reproduction. 2021;15(1):5-21. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.212
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