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

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

Detailed Description
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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.

Official Title
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An Observational Study FOLLITROPIN Comparing the Efficacy of Follitropin Alpha Biosimilar: the Real-world Data

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

Intervention / Treatment
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* Drug: Follitropin Alfa
* Drug: Follicle Stimulating Hormone/Luteinizing Hormone
* Drug: Follitropin Alfa
* Drug: Follitropin Alfa
* Drug: Follicle Stimulating Hormone/Luteinizing Hormone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH<br>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. | Drug: Follitropin Alfa<br>* Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH or agonist of GnRH.<br>* Other names: Biosimilar;|
| Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH<br>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. | Drug: Follicle Stimulating Hormone/Luteinizing Hormone<br>* Subcutaneous injection of follitropin alpha biosimilar, with daily dose 100-300 IU for at least 5 days, than added another gonadotropin for a maximum of 10 days, using antagonists of GnRH or agonist of GnRH.<br>* Other names: Follitropin alfa biosimilar;|
| Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH<br>The OS protocols included: monotherapy protocols with using only follitropin alpha biosimilar and antagonists of GnRH. | Drug: Follitropin Alfa<br>* Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH only for suppression.<br>* Other names: Follitropin alfa biosimilar;|
| Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH<br>The OS protocol included: monotherapy protocols with using only follitropin alpha biosimilar and agonists of GnRH. | Drug: Follitropin Alfa<br>* Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using agonists of GnRH only for suppression.<br>* Other names: Follitropin alfa biosimilar;|
| The overall protocols<br>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 | Drug: Follicle Stimulating Hormone/Luteinizing Hormone<br>* Overall ovarian stimulation protocols with follitropin alpha biosimilar for at least 5 days+other recombinant and menotropins and short (antagonists of GnRH) or long protocol (agonist of GnRH).<br>* Other names: Follitropin alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Oocytes Retrieved | 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). | From date of start of ovarian stimulation with follitropin alpha up to 15 days | 
| Percentage of Participants With Ongoing Clinical Pregnancy Per 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). | At least 6 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Mature Oocytes | 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). | From date of start of ovarian stimulation with follitropin alpha up to 15 days | 
| Number of Fertilized Oocytes | 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). | From date of start of ovarian stimulation with follitropin alpha up to 16 days | 
| Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 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). | From date of start of ovarian stimulation with follitropin alpha up to 16 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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follitropin alpha, follicle-stimulating hormone, in vitro fertilization, assisted reproductive technologies, biosimilar, follitropin alfa, real-world data