follitropin alfa
Regulatory sources consulted
Approved indications
- Ovulation induction in women with oligo-ovulation or anovulation not due to primary ovarian failure.
- Development of multiple follicles in assisted-reproduction programs.
- Induction of spermatogenesis, with hCG, in men with hypogonadotropic hypogonadism.
Contraindications
Absolute
- Hypersensitivity to FSH or excipients, primary gonadal failure, uncontrolled thyroid, adrenal, or pituitary endocrinopathy, or hypothalamic/pituitary tumor.
- In women: undiagnosed genital bleeding or ovarian cyst/enlargement of undetermined origin.
Clinical warnings
- Major warning · Ultrasound and hormonal monitoring are required. Withhold hCG and follow protocol if ovarian hyperstimulation syndrome risk develops. — FDA/DailyMed, set_id ae85b9c3-e7eb-4981-a5d9-346050e8f189
- Major warning · It may cause ovarian hyperstimulation syndrome, torsion, thromboembolism, multiple or ectopic pregnancy, pregnancy loss, and severe allergic reactions. — FDA/DailyMed, set_id ae85b9c3-e7eb-4981-a5d9-346050e8f189
Drug interactions
- ModeratehCG or clomiphene citrate
Mechanism: Concomitant use may potentiate the follicular response.
Recommendation: Individualize and closely monitor ovarian response; do not increase the dose without specialist assessment.
CIMA/AEMPS, ficha técnica 95001021https://cima.aemps.es/cima/dochtml/ft/95001021/FT_95001021.html
- ModerateGnRH agonists or antagonists
Mechanism: Pituitary desensitization may increase the follitropin alfa dose needed to obtain an adequate ovarian response.
Recommendation: Adjust only according to ultrasound and hormonal monitoring by a fertility specialist.
CIMA/AEMPS, ficha técnica 95001021https://cima.aemps.es/cima/dochtml/ft/95001021/FT_95001021.html
Adverse events
Common (≥1%)
Headache · Abdominal or pelvic pain · Ovarian cyst · Nausea · Injection-site reaction · Acne or gynecomastia in men
Rare but serious
Severe ovarian hyperstimulation syndrome · Thromboembolism · Anaphylaxis
Pregnancy and lactation
Not indicated during pregnancy or breastfeeding.
Recent literature (PubMed)
Is ovarian stimulation with follitropin delta in its individualised fixed-dose regimen at least as efficacious as follitropin alfa in a conventional dosing regimen in Asian population? Ovarian stimulation with individualised follitropin delta dosing resulted in a non-inferior ongoing pregnancy rate, a significantly higher live birth rate and a significantly lower incidence of early ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions compared to conventional follitropin alfa dosing. Previous randomised controlled trials conducted in Japan as well as in Europe, North- and South America have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum anti-Müllerian hormone (AMH) level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates. Randomised, controlled, multi-centre, assessor-blind trial conducted in 1009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle. Randomisation was stratified by age (<35, 35-37, 38-40 years). The primary endpoint was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority limit -10.0%; analysis adjusted for age stratum). The follitropin delta treatment consisted of a fixed daily dose individualised according to each patient's initial AMH level and body weight (AMH <15 pmol/l: 12 μg; AMH ≥15 pmol/l: 0.19 to 0.10 μg/kg; min-max 6-12 μg). The follitropin alfa dose was 150 IU/day for the first 5 days with subsequent potential dose adjustments according to individual response. A GnRH antagonist protocol was applied. OHSS was classified based on Golan's system. Women with an ongoing pregnancy were followed until live birth and 4 weeks after. The number of oocytes retrieved was significantly (P < 0.001) lower with individualised follitropin delta versus conventional follitropin alfa (10.0 ± 6.1 vers
How do ovarian responses using conventional dosing for follitropin delta 15 µg/day compare with follitropin alfa 225 IU/day in women undergoing ovarian stimulation? The ADAPT-1 trial demonstrates similar ovarian responses with follitropin delta 15 µg/day and follitropin alfa 225 IU/day starting doses in a conventional dosing regimen. Follitropin delta, a recombinant FSH (rFSH), is currently approved for ovarian stimulation using an individualized fixed daily dose based on serum anti-Müllerian hormone (AMH) and bodyweight (maximum 12 µg/day for first cycle and 24 µg/day in subsequent cycles). Other rFSHs, such as follitropin alfa, conventionally apply a starting dose of 150-225 IU, fixed for the initial days of stimulation, after which dose adjustments can be made (maximum 450 IU/day). Ovarian stimulation with follitropin delta 10 µg/day provides a similar ovarian response to follitropin alfa 150 IU/day for serum concentration and number of follicles ≥12 mm. ADAPT-1 was a randomized, accessor-blinded, multicentre trial comparing efficacy and safety of a starting dose of follitropin delta 15 µg/day with follitropin alfa 225 IU/day in conventional dosing regimens. The primary endpoint was the number of oocytes retrieved; mean difference between treatment groups was estimated using a negative binomial regression model (treatment and serum AMH level as factors). During the follow-up period, clinical pregnancies resulting from the first fresh/frozen transfers within 3 months of the start of stimulation, and ovarian hyperstimulation syndrome (OHSS) rates were assessed. Participants, 18-40 years, undergoing IVF/ICSI could enrol at specialist reproductive clinics in Austria, France, Italy, Spain, and the United Kingdom for ovarian stimulation if they had no contraindications for treatment with a starting gonadotropin dose of 225 IU/day. Patients could enrol if they reported infertility for at least 1 year if ≤37 years and at least 6 months for those >37 years, and regular me
The aim of this study was to provide an updated meta-analysis assessing the therapeutic equivalence between follitropin alfa biosimilars and the reference medication in women undergoing assisted reproductive technologies (ART). The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) for binary outcomes and the mean difference (MD) for continuous outcomes along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and χ2 tests. No differences were found concerning the number of oocytes retrieved at ovum pick-up, the primary endpoint recommended by the European Medicines Agency (EMA) (MD -0.04 CI [-0.78, 0.71], P=0.92). A significantly higher clinical pregnancy rate (OR 0.70 CI [0.53, 0.93], P=0.01) was observed in the reference product group in comparison to the biosimilar follitropin alfa, whereas no statistically significant differences were found for biochemical pregnancy rate, take home baby rate, total follitropin alfa dose, duration of stimulation, and ovarian hyperstimulation syndrome risk. The non-inferiority of biosimilar formulations in comparison to the reference product, with respect to number of oocytes retrieved at ovum pick-up, was shown.
Understanding the variability in ovarian response following administration of follicle-stimulating hormone medications in women undergoing in vitro fertilization may help inform prescribing decisions. A systematic review was conducted to compare the number of retrieved oocytes and fertility outcomes following the administration of different follicle-stimulating hormone medications. Databases were searched from inception to November 2024, including studies that compared two follicle-stimulating hormone medications, including follitropin alfa, follitropin beta, follitropin delta, and urofollitropin. Meta-analyses were performed in random effects models with the restricted maximum likelihood method. From 3867 identified articles, 26 (12613 participants) were included. More oocytes were retrieved with follitropin alfa compared to beta (mean difference 0.64, 95% CI 0.09-1.19). Compared to follitropin delta, more oocytes were retrieved with follitropin alfa and beta (1.38, 95% CI 0.09-2.67, and 1.40, 95% CI 0.41-2.39, respectively); however, higher total doses of follitropin alfa and beta were administered (199.29 IU, 95% CI 43.15-355.43 and 181.08 IU, 95% CI 55.67-306.49, respectively), and the risk of hyperstimulation increased (risk ratios 1.42, 95% CI 1.04-1.96 and 1.75, 95% CI 1.15-2.70, respectively). More oocytes were retrieved with urofollitropin compared to follitropin beta (1.12, 95% CI -1.63 to -0.62), with higher total doses of urofollitropin administered (782.32 IU, 95% CI -1493.79 to -70.85). Variability in ovarian response and hyperstimulation rates across the medications decreased when similar total doses were administered. Fertilization, pregnancy, and live birth rates were similar across the medications, despite differences in the number of retrieved oocytes. Additional research is required to evaluate oocyte quality across follicle-stimulating hormone medications.
This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings.