An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data

Completed

Conditions: Reproductive Issues
Reproductive Disorder
Gynecologic Disease
Fertility Disorders
Fertility Issues
IVF

Interventions: Drug: Follicle Stimulating Hormone/Luteinizing Hormone
Drug: Follitropin Alfa

Registration Number: NCT04854707

Lead Sponsor: IVFarma LLC

Brief Summary: Aim to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 5484

Inclusion Criteria

Women with established causes of infertility and indications for the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation "On the use of assisted reproductive technologies, contraindications and limitations to their use" No. 107 n dated August 30, 2012.
Infertility due to female and/or male factor.
Presence of ovaries accessible for aspiration of follicles.
Anatomical and functional capability of uterus to bear pregnancy.

Exclusion Criteria

Women with established contraindications to the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation "On the use of assisted reproductive technologies, contraindications and limitations to their use" No. 107 n dated August 30, 2012.
Presence of pregnancy
Hypersensitivity to follitropin alfa or excipients.
Ovarian cysts (not associated with polycystic ovarian syndrome), uterine hemorrhage of unclear etiology
Premature ovarian failure
Presence of clinically significant systemic disease
Presence of chronic cardiovascular, hepatic, renal or pulmonary disease
Neoplasia
Narcomania, alcoholism

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH	Follicle Stimulating Hormone/Luteinizing Hormone	The OS protocols included: mixed protocols (recombinant with addition of urinary-derived gonadotropins) and antagonists/agonists of GnRH (ganirelix, cetrorelix, triptorelin, buserelin), where follitropin alpha biosimilar used for at least 5 days during OS.
The overall protocols	Follicle Stimulating Hormone/Luteinizing Hormone	The OS protocols included: (1) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH, (2) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH
Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH	Follitropin Alfa	The ovarian stimulation (OS) protocols included monotherapy protocols with using follitropin alpha biosimilar only and antagonists/agonists of of gonadotropin-releasing hormone (GnRH): ganirelix, cetrorelix, triptorelin, buserelin.
Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH	Follitropin Alfa	The OS protocol included: monotherapy protocols with using only follitropin alpha biosimilar and agonists of GnRH.
Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH	Follitropin Alfa	The OS protocols included: monotherapy protocols with using only follitropin alpha biosimilar and antagonists of GnRH.

Primary Outcome Measures

Name	Time	Method
Number of Oocytes Retrieved	From date of start of ovarian stimulation with follitropin alpha up to 15 days	The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the ovulation inducer (HCG or GnRH-agonist). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer	At least 6 weeks after embryo transfer	Ongoing clinical pregnancy per embryo transfer (detection of gestational sac and heartbeat from 6 weeks after transfer), n (ongoing pregnancy rate per transfer with known outcome, %). Due to delayed embryo transfers, the analysed population for "Ongoing clinical pregnancy per embryo transfer" was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2007 embryo transfers (1542 with known outcome); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2213 embryo transfers (1800 with known outcome); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 1809 embryo transfers (1466 with known outcome) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 404 embryo transfers (334 with known outcome).

Secondary Outcome Measures

Name	Time	Method
Total Dose of Follitropin Alpha Biosimilar Protocol, IU	From date of start of ovarian stimulation with follitropin alpha up to 16 days	Mean dose of follitropin alpha biosimilar for ovarian stimulation. Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Number of Mature Oocytes	From date of start of ovarian stimulation with follitropin alpha up to 15 days	Mature oocytes (MII stage of development). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Number of Fertilized Oocytes	From date of start of ovarian stimulation with follitropin alpha up to 16 days	Fertilization rate (FR) is percentage of transformation of oocytes into two pronuclei (presence of two pronuclei: zygotes with 2PN). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).

Trial Locations

Locations (33): Clinical Hospital "Mother and Child"
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Ufa, Russian Federation
Clinic "Mother and Child" Krasnodar
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Krasnodar, Russian Federation
Clinic "Mather and Child" Lefortovo
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Moscow, Russian Federation
Clinic "Mather and Child" Savelovskaya
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Moscow, Russian Federation
Clinic "Mother and Child"
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Nizhny Novgorod, Russian Federation
Clinical Hospital MD GROUP (Perinatal Center on Sevastopolskiy)
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Moscow, Russian Federation
AltraVita IVF clinic
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Moscow, Russian Federation
Clinical Hospital Lapino
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Moscow Oblast, Russian Federation
Center of Reproductive Medicine and Genetics "Nova Clinic"
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Moscow, Russian Federation
Medika-2
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Novokuznetsk, Russian Federation
Center for reproductive medicine, Barnaul
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Barnaul, Russian Federation
Clinic "Mother and Child" Perm
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Perm, Russian Federation
Clinic "Mother and Child" Volgograd
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Volgograd, Russian Federation
Center for reproductive medicine, Krasnoyarsk
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Krasnoyarsk, Russian Federation
Center for reproductive medicine, Novosibirsk
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Novosibirsk, Russian Federation
Clinical Hospital "Avicenna"
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Novosibirsk, Russian Federation
Ceter for reproductive medicine, Omsk
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Omsk, Russian Federation
Clinic "Mother and Child" Rostov-on-Don
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Rostov-on-Don, Russian Federation
Clinic "Mather and Child"
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Ryazan', Russian Federation
Clinic "Mather and Child" Tula
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Tula, Russian Federation
Clinic "Mother and Child" Saint-Petersburg
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Saint Petersburg, Russian Federation
Clinic "Mather and Child" Vladivostok
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Vladivostok, Russian Federation
Clinic "Mother and Child" Vladimir
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Vladimir, Russian Federation
Clinic "Mother and Child" South-West
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Moscow, Russian Federation
Center for reproductive medicine, Irkutsk
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Irkutsk, Russian Federation
Clinical Institute of Reproductive Medicine
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Ekaterinburg, Russian Federation
Clinic "Mother and Child" Kostroma
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Kostroma, Russian Federation
Clinic "Mother and Child" Kazan
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Kazan, Russian Federation
Clinic "Mother and Child" Khodynskoe Pole
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Moscow, Russian Federation
Clinic "Mother and Child" Kuntsevo
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Moscow, Russian Federation
"Genesis" Reproduction Centre
🇷🇺
Saint Petersburg, Russian Federation
Clinic "Mother and Child" Voronezh
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Voronezh, Russian Federation
Clinic "Mother and Child" Yaroslavl
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Yaroslavl, Russian Federation