The continuum of ovarian response leading to BIRTH, a real world study of ART in Spain

Abstract

Background: The first biosimilar of recombinant follicle stimulating hormone (rFSH) launched in Europe was Bemfola® in 2014 following a clinical development programme demonstrating efficacy and safety to the satisfaction of the European Medicines Agency. Since then the increasing use of biosimilar rFSH has provided the opportunity to study both effectiveness across the whole population and the variation of rFSH use during routine clinical care in a real-world setting in Spain. Methods: This is a real-world study of 1222 women treated in 26 assisted reproduction treatment centres throughout Spain providing experience of the use of a biosimilar recombinant follicle stimulating hormone in four distinct populations. The four populations studied were poor responders, suboptimal responders, normal responders and oocyte donors. The primary endpoint was the total number of oocytes retrieved. Secondary endpoints included number of days of rFSH stimulation, total dose of rFSH administered, number of MII oocytes, number of fertilized oocytes, quality of embryos, number of embryos transferred, implantation rates, clinical pregnancy rates following embryo transfer, number of multiple pregnancies and number of serious adverse reactions, including moderate-to-severe OHSS. Results: Differences were seen across the populations both in the characteristics of the women and ART outcomes suggestive of a continuum of fertility prognosis. In the poor responders, suboptimal responders, normal responders and oocyte donor populations the mean age in years was 39.9 (±SD 3.4), 38.4 (±SD 2.9), 34.4 (±SD 3.3) and 26 (±SD 4.6) respectively and number of oocytes retrieved was 4.1 (±SD 2.7), 8.6 (±SD 6.0), 12.2 (±SD 7.2) and 19.5 (±SD 9.5) respectively. The proportion of embryos graded as best quality was 18.5%, 33.0% and 43.8%, and graded as worst quality was 20.4%, 5.8% and 5.8% for poor responders, suboptimal responders and normal responders respectively. In a similar pattern, for poor responders, suboptimal responders and normal responders the implantation rates were 16.0%, (8/50), 22.4% (49/219), 30.6% (97/317) respectively and clinical pregnancy rates were 23.2% (10/43), 30.4% (59/194) and 37.0% (114/308) respectively. Adverse events were reported in only 7 of 1222 women (0.6%). Conclusions: Overall the results were consistent with the national ART results reported for Spain, hence this study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting. Trial registration: ClinicalTrials.gov identifier-NCT02941341.

Determining the cost-effectiveness of follitropin alfa biosimilar compared to follitropin alfa originator in women undergoing fertility treatment in France

“…Differences in type of pituitary desensitization used may contribute to differences in costs at this stage but were not the driving factor. Results displayed here are supported by similar cost savings analysis looking at gonadotropin costs only [29] , which aligns with the clinical equivalence between the two r-hFSH [5] , [7] , [8] , [9] , [10] and a previous cost effectiveness study which shows cost per live-birth is lower with follitropin alfa biosimilars than with follitropin alfa originator [18] .…”

“…This study investigates the cost-effectiveness of follitropin alfa biosimilar versus the originator in a French healthcare setting using inputs from real-world data and CLBR. As follitropin alfa biosimilar has previously shown non-inferiority to the originator in terms of oocyte retrieval and CLBR per ART ovarian stimulation cycle [7] , [8] , [9] , [10] , [11] , which is supported by the recommendation of interchangeability within the EU of all biosimilars with their originator [28] , differences in the overall ART costs originate mostly from the r-hFSH drug costs.…”

“…It includes all relevant clinical and economic events in ART management following one OS using either follitropin alfa originator (Gonal-f®, Merck KGaA, Darmstadt, Germany) or follitropin alfa biosimilar (Bemfola®, Gedeon Richter Plc, Budapest, Hungary). Clinical data within the model were taken from the REOLA study [7] , it used different starting dose categories which are effective in defining relevant real-world populations, as treating doctors define starting dose based on anticipated ovarian responsiveness [7] , [10] . The model follows fresh transfers and frozen transfers until live-birth or treatment discontinuation to provide the CLBR [17] , allowing the cost per CLB to be reported.…”

“…The follitropin alfa biosimilar Bemfola® (Gedeon Richter Plc, Budapest, Hungary) was the first r-hFSH alpha biosimilar launched in France in 2015 [5] , [6] . Several clinical trials and real-world studies demonstrated similar efficacy and safety between this follitropin alfa biosimilar and alternative FSH options [7] , [8] , [9] , [10] , [11] , and concluded that there are no clinically relevant differences [5] . The REOLA real-world study investigated cumulative live-birth rates (CLBR), the endpoint of interest [12] , [13] , and reported no apparent difference between the follitropin alfa biosimilar and originator in terms of CLBR according to starting dose of rFSH [7] .…”

Risk of dosing errors in ART treatment: user experience of single- vs multi-use follitropin alfa pens

“…During controlled ovarian stimulation for assisted reproductive technologies (ART), several different medications and dosing regimens are often used [1]. The medications involved include gonadotropin treatment in the form of FSH, which is self-injected daily, usually over a period of 9 to 11 days [2,3]. FSH is available in many different forms and administered through different systems, such as vials and syringes; disposable, single-use, pre-filled pens; multi-use pre-filled pens; and re-useable pens requiring insertion of cartridges [4][5][6][7].…”