OBJECTIVE: To investigate whether the ovarian stimulation with follitropin delta in an individualized algorithm-based manner is inferior to recombinant human-follicle stimulating\'s follitropin alfa or follitropin beta conventional dosing regarding a series of established primary endpoints.
METHODS: We conducted a registered systematic review (CRD42024512792) on PubMed-MEDLINE, Web of Science™, Cochrane Database of Systematic Reviews, and Scopus. Our search was designed to cover all relevant literature, particularly randomized controlled trials. We critically and comparatively analyzed the outcomes for each primary endpoint based on the intervention, reflected by the positive βhCG test, clinical pregnancy, vital pregnancy, ongoing pregnancy, live birth, live birth at 4 weeks, and multiple pregnancies.
RESULTS: Six randomized controlled trials were included in the quality assessment as priority manuscripts, revealing an 83.3% low risk of bias. Follitropin delta led to non-significant differences in each parameter of interest from positive βhCG test (691; 53.44% vs. 602; 46.55%), ongoing pregnancies (603; 53.79% vs. 518; 46.20%), clinical and vital pregnancies (1,073; 52.80% vs. 959; 47.19%), to live birth and at 4 weeks (595; 54.14% vs. 504; 45.85%) with only 2 losses, and even multiple pregnancies (8; 66.66% vs. 4; 33.33%). However, follitropin delta was well-tolerated among hypo- and hyper-responders without significant risk of ovarian hyperstimulation syndrome and/or preventive interventions in contrast with follitropin alfa or follitropin beta.
CONCLUSIONS: The personalized individualized-based algorithm dosing with follitropin delta is non-inferior to conventional follitropin alfa or follitropin beta. It is as effective in promoting a similar response in women without significant comparable adverse effects.

BACKGROUND: Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.
RESULTS: A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6-9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0-4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0-6.0mcg FD.
CONCLUSIONS: Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.