Abstract
BackgroundGonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa) and recombinant human luteinizing hormone (r-hLH; lutropin alfa) can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike.MethodsThis study investigated whether follitropin alfa (GONAL-f (R)), as lyophilized powder for reconstitution or solution from the GONAL-f (R) (filled-by-mass [FbM]) Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU) lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively.ResultsFollitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups.ConclusionFollitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to enable physicians to administer ratios of r-hFSH and r-hLH in the IU range from 3:1 to 8:1. Mixing of recombinant formulations offers flexibility for patients receiving follitropin alfa and lutropin alfa for ART protocols in clinical practice.
Highlights
Gonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols
Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU in mL follitropin alfa (75 IU) lyophilized powder to enable physicians to administer ratios of Recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) in the IU range from 3:1 to 8:1
Ratio Group 1: 75 IU in 1 mL follitropin alfa (75 IU) plus follitropin alfa/lutropin alfa 150 IU/75 IU (r-hFSH:r-hLH ratio 3:1) Step 1: A vial containing follitropin alfa 75 IU lyophilized powder was reconstituted with 1 mL of Water for injection (WFI) using a 1 mL plastic syringe with 22 GA × 1" needle
Summary
Gonadotrophins are routinely administered in assisted reproductive technology (ART) treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa) and recombinant human luteinizing hormone (r-hLH; lutropin alfa) can be administered individually or in a fixed combination. Recombinant human FSH (r-hFSH; follitropin alfa) and LH (r-hLH; lutropin alfa) can be administered independently or in combination, in accordance with individual patient needs. Various injection devices have been developed to simplify administration of gonadotrophins and allow patients to self-administer treatment [2]. Follitropin alfa (filled-bymass [FbM]) is provided in ready-to-use, prefilled pens that are designed for self-administration by patients [2,3]. The variety of commercially available preparations accommodates individualized dosing for diverse protocols for ovulation induction or controlled ovarian stimulation
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have