P–669 “Follitropin”: A retrospective, observational study comparing the efficacy of follitropin alpha biosimilar therapy in different ovarian stimulation protocols: real-world data
Authors: Polzikov M , Kamilova D , Ovchinnikova M , Mayasina E , Boyarsky K , Nikitin S , Bendusov I , Ganikhina M , Barakhoeva Z , Osina E , Ablyaeva E , Khetagurova D , Ushakova T , Blinov D 
Published: August 2021

Abstract

Study question
To investigate the therapeutic efficacy of follitropin alpha biosimilar therapy in nonselected patients undergoing IVF.

Summary answer
This large retrospective study demonstrated similar therapeutic efficacy for follitropin alpha biosimilar therapy in women who underwent ovarian stimulation (OS) using different protocols.

What is known already
Based on data from the last meta-analyses (Budani et al., 2020), follitropin alpha biosimilars showed similar efficacy and safety in randomized controlled trials aimed at proving the therapeutic equivalence in terms of oocytes retrieved in women undergoing OS. In most cases, normogonadotrophic patients were enrolled in such studies without any endocrine or ovarian disturbances. The absence of real-world data can be compensated by additional post-marketing studies aimed at investigating the efficacy of biosimilars in different OS protocols using antagonists and agonists of GnRH and OS with mixed gonadotropins.

Study design, size, duration
A retrospective, observational, anonymized cohort study conducted at 35 IVF clinics in Russia, named “FOLLITROPIN”, compared the efficacy of OS in 2020. The OS protocols analysed where follitropin alpha biosimilar (Primapur®) was applied for at least 5 days. All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins. No inclusion or exclusion criteria were applied. Overall, 5484 OS protocols were analysed.

Participants/materials, setting, methods
The efficacy of 5484 OS protocols was calculated, and two subgroups were extracted: (1) mixed gonadotropin OS protocols (N = 2625) vs monotherapy with Primapur® (N = 2859); (2) GnRH antagonist OS (N = 2183) vs GnRH agonist (N = 676) using only Primapur®. Demographic and clinical characteristics: (1) Age 34.9±4.8 vs 32.9±4.7 (p &lt; 0.001), BMI 23.9±4.7 vs 23.6±4.5 (p &lt; 0.001), IVF attempt 1.4±0.7 vs 1.3±0.6 (p &lt; 0.001); (2) Age 32.9±4.6 vs 33.1±4.9 (p = 0.449), BMI 23.7±4.6 vs 23.1±4.5 (p = 0.019), and IVF attempt 1.2±0.5 vs 1.4±0.9 (p &lt; 0.001).

Main results and the role of chance
The total efficacy of OS with Primapur®: oocytes retrieved: 9.5±7.2, MII: 6.8±6.6, 2PN: 6.1±5.8, clinical pregnancy per ET (PR) 6 weeks after ET: 38.4%. Subgroup 1 analysis: oocytes retrieved: 8.6±6.8 vs 10.3±7.4 (p &lt; 0.001), MII: 6.7±6.2 vs 7.7±6.9 (p &lt; 0.001), 2PN: 5.8±5.2 vs 7.2±6.2 (p &lt; 0.001). There were statistically significant differences between oocyte yields in mixed vs monotherapy protocols due to subgroup differences, including age, BMI and IVF attempts. No statistically significant differences were found for PR in subgroup 1: 39.3% [95% CI: 36.9–41.7%] vs 37.6% [95% CI: 35.3–39.8%] (p = 0.314). The major accompanying gonadotropin in the mixed protocol was menotropin (75% for mixed OS protocols). Subgroup 2 analysis: oocytes retrieved: 10.5±7.5 vs 9.6±7.0 (p = 0.032), MII: 7.6±6.9 vs 6.7±5.7 (p &lt; 0.001), 2PN: 7.3±6.3 vs 5.7±5.0 (p &lt; 0.001). There were statistically significant differences between oocyte yields in GnRH antagonist vs GnRH agonist monotherapy due to subgroup differences, including BMI and IVF attempts. No statistically significant differences were found for PR in subgroup 2: 37.9% [95% CI: 35.5–40.5%] vs 35.9% [95% CI: 30.8–41.1%] (p = 0.482). All medicines were well tolerated at the injection site, and no serious adverse reactions were reported. This large retrospective cohort study in a nonselected population demonstrated similar clinical efficacy for follitropin alpha biosimilar therapy.

Limitations, reasons for caution
The real-world patient data analysed in this study were representative, showing the ability of follitropin biosimilars to develop both folliculogenesis and clinical pregnancy in a nonselected population. Additional comparative studies are needed to confirm the efficacy of the biosimilars in patients with classified types of infertility causes, including unexplained infertility.
Wider implications of the findings: In this study, we demonstrated the therapeutic efficacy of biosimilars in terms of oocyte yield and clinical pregnancy development in women undergoing different OS protocols. Further large-scale studies with known hormonal levels before and during OS, as well as the micro- and macronutrient status of both parents, are needed.

Trial registration number
None