An Observational Study "FOLLITROPIN" Comparing the Efficacy of Follitropin Alpha Biosimilar: the Real-world Data
Conditions: Reproductive Issues, Reproductive Disorder, Fertility Disorders, Fertility Issues, Gynecologic Disease, IVF
Sponsor: IVFarma LLC

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STUDY SUMMARY 
Study title: 
An Observational Study "FOLLITROPIN" Comparing the Efficacy of 
Follitropin Alpha Biosimilar: The Real-world Data 
Study type: 
Phase IV 
Test product 
TN: Primapur®  
INN: follitropin alpha 
Dosage form: solution for subcutaneous injection 
Pharmaceutical form: pre-filled disposable syringe containing follitropin  
alpha  66 μg (900 IU), 33 μg (450 IU), 22 μg (300 IU), 
Manufacturer: Zavod Medsintez LLC, Russia 
Ethical and legal aspects: 
This study conducted in strict accordance with the following international 
and Russian documents: 
1. Principles of the World Medical Association Declaration of Helsinki 
(Fortaleza, Brazil, 2013).  
2. Constitution of the Russian Federation.  
3. Federal Law “On the fundamentals of protecting the health of citizens 
in the Russian Federation” dated November 21, 2011 No. 323-FZ, 
2011.  
4. Federal Law “On the Circulation of Medicines” No. 61-FZ dated 12 
April 2010. 
5. Federal Law "On personal data" No. 152-FZ dated July 27, 2006. 
6. 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. 
Study goals: 
To investigate the efficacy of follitropin alpha biosimilar 
therapy (Primapur®) in nonselected real-world population. 
Study objectives: 
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. 
The  
ovarian  
stimulation  
(OS)  
protocols  
included: 
monotherapy  protocols  with  using  only  follitropin alpha 
biosimilar  (Primapur®);  mixed  protocols  (recombinant  and 
urinary-derived  gonadotropins)  and follitropin alpha biosimilar; 
short protocols  with  using  antagonists  of  gonadotropin-
releasing  hormone  (GnRH)  and  long  protocols  with 

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GnRH  agonists.  The stimulation protocols were analyzed 
with Primapur® application for at least 5 days. 
Study design: 
Retrospective, observational 
(non-interventional), anonymized, 
cohort study  
Number of patients 
5500 patients 
Study centers 
35 in vitro fertilization (IVF) clinics in the Russian Federation 
Study population: 
Women aged 20-43 with established causes of infertility and indications 
for the use of assisted reproductive technologies (ART) and ovarian 
stimulation. 
Inclusion criteria: 
1. 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. 
2. Infertility due to female and/or male factor. 
3. Presence of ovaries accessible for aspiration of follicles. 
4. Anatomical and functional capability of uterus to bear pregnancy. 
 
Exclusion criteria: 
 
1. 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. 
2. Presence of pregnancy 
3. Hypersensitivity to follitropin alpha and other gonadotropins or 
excipients. 
4. Ovarian cysts (not associated with polycystic ovarian syndrome), 
uterine hemorrhage of unclear etiology 
5. Premature ovarian failure 
6. Presence of clinically significant systemic disease 
7. Presence of chronic cardiovascular, hepatic, renal or pulmonary 
disease 
8. Neoplasia 
9. Narcomania, alcoholism 
 
Dosage and duration of 
treatment; route of 
administration: 
Drug: Follicle Stimulating Hormone/Luteinizing Hormone 
Overall ovarian stimulation protocols with follitropin alpha 
biosimilar for at least 5 days (100-300 IU) and other recombinant 
follitropins and menotropins, short (antagonists of GnRH) or long 
protocols (agonist of GnRH).  
Concomitant therapy:  
 
All patients received approved medication by physician, accordingly 
to National guidelines. 

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Efficacy evaluation criteria: Study endpoints per patient: 
 
Primary point:  
• 
Total number of aspirated oocytes. 
• 
Incidence of clinical pregnancies (up to 6 weeks after the embryo(s) 
transfer). 
 
Secondary points:  
• 
Number of mature oocytes (MII stage). 
• 
Number of fertilized oocytes (zygotes with 2PN). 
• 
Total dose of a follitropin alpha biosimilar injected (IU). 
Safety evaluation criteria: 
• Incidence 
of 
serious 
adverse 
events 
e.g., 
severe 
ovarian 
hyperstimulation syndrome (%) with hospitalization. 
• Incidence of the adverse event, such as injection site pain (%). 
Groups/arms to compare: 
1. Monoprotocols: follitropin alpha biosimilar only and 
antagonists/agonists of GnRH 
(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). 
2. Mixed 
protocols: 
recombinant 
and 
urinary-derived 
gonadotropins and antagonists/agonists of GnRH. 
(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). 
3. Monoprotocols: follitropin alpha biosimilar only and 
antagonists of GnRH 
(The OS protocols included: monotherapy protocols with using only 
follitropin alpha biosimilar and antagonists of GnRH). 
4. Monoprotocols: follitropin alpha biosimilar only and agonist 
of GnRH 
(The OS protocol included: monotherapy protocols with using only 
follitropin alpha biosimilar and agonists of GnRH). 
5. The overall protocols 
(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). 
 
 
 
 
 
 

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Flow chart: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcome Measures: 
Primary outcomes: 
1. Number of Oocytes Retrieved 
2. Percentage of Participants With Ongoing Clinical Pregnancy Per 
Embryo Transfer 
Secondary outcomes: 
1. Number of Mature Oocytes 
2. Number of Fertilized Oocytes 
3. Total Dose of Follitropin Alpha Biosimilar Protocol 
Groups/Arms to compare 
1. Mixed protocols: recombinant and urinary-derived gonadotropins 
and antagonists/agonists of GnRH AND Monoprotocols: 
follitropin alpha biosimilar only and antagonists/agonists of 
GnRH 
2. Monoprotocols: follitropin alpha biosimilar only and antagonists 
of GnRH AND Monoprotocols: follitropin alpha biosimilar only 
and agonist of GnRH 
3. Overall protocols – descriptive statistics for all in vitro 
fertilization protocols 
 
Statistical processing of 
data: 
Description of methods of statistical data processing 
The quantitative data obtained during the study will be tested for 
normal distribution, using the Shapiro-Wilk test and, if necessary, the F-
test of equality of variances. For variables corresponding to the normal 
distribution, mean values and standard deviation of the mean will be 
calculated; Quantitative data not corresponding to the normal distribution 
will be described using the median and interquartile interval. Qualitative 
variables will be described using absolute and relative frequencies 
(percentages). 
Overall 
protocols 
Mixed 
protocols 
Monoprotocols 
Monoprotocols 
with antagonist 
GnRH 
Monoprotocols 
with agonist 
GnRH 

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In order to compare two groups of normally distributed quantitative 
data, the Student's t-test will be used; if quantitative data distribution 
differs from normal values, the Mann-Whitney U test will be used. For 
intergroup comparisons by qualitative characteristics, the Fisher's exact 
test will be used.  
Applicable significance level 
In this study, the indicators are considered statistically significant at 
the bilateral p-value level <0.05.