A multicentric real-world observational study to describe the use and efficacy of follitropin delta for IVF/ICSI procedures in patients at risk of hypo-response

BackgroundAround 20% of patients undergoing assisted reproductive technology are at risk of hypo-response to ovarian stimulation. The aim of this study was to describe the real-world use of follitropin delta for ovarian stimulation in these patients, as defined by POSEIDON groups 3 and 4 [an anti-Müllerian hormone (AMH) level of <1.2 ng/ml].Materials and methodsThis study was a post-hoc analysis of participants from DELTA, a multi-centre, prospective, observational study conducted in normal care settings in fertility clinics at 14 active sites in France. A subset of 35 patients at risk of hypo-response to ovarian stimulation (mean AMH 0.7 ± 0.29 ng/ml) and treated with follitropin delta were included. Patients were followed for 10–11 weeks after the first fresh or frozen embryo transfer in case of subsequent pregnancy, and data on real-world follitropin delta use collected.ResultsMost patients (92.9%) had undergone their first IVF or ICSI. The prescribed daily dose was usually based on the approved algorithm (N = 26; 74.3%) with a mean daily dose of 14.2 ± 4.1 mcg, resulting in a mean total dose of 187.7 ± 135.6 mcg. The mean duration of ovarian stimulation was 11.6 ± 6.7 days with no premature discontinuations, while the mean number of oocytes retrieved among patients that started stimulation was 6.3 ± 4.3. A fresh transfer was performed for 21 patients (84.0%), with a mean of 1.04 ± 0.98 embryos transferred per patient. Seven patients (20.0%) achieved an ongoing pregnancy (28% per transfer). No adverse drug reactions were reported.ConclusionsThe results describe the real-world use of follitropin delta and demonstrate its suitability for POSEIDON group 3 and 4 patients. These data complement clinical trial outcomes, supporting clinician decision-making and improving IVF/ICSI outcomes

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally

Prospective multicenter observational real-world study to assess the use, efficacy and safety profile of follitropin delta during IVF/ICSI procedures (DELTA Study)

International audienceObjective: To describe the use, efficacy and safety profile of follitropin delta in women undergoing IVF/ICSI in routine clinical practice after one treatment cycle.Study design: This was a French multicenter, prospective, observational study conducted in 14 fertility centers between June 2020 and June 2021. During this period, 248 women undergoing IVF or ICSI were treated with follitropin delta for the first time. Women were followed up to 10-11 weeks after the first fresh or frozen embryo transfer. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy, and adverse drug reactions in routine clinical practice.Results: The analyzable population consisted of 223 patients with mean ± SD age of 33.0 ± 4.4 years, body weight of 65.7 ± 11.8 kg, and the median (IQR) AMH level was 2.6 (1.5-4.0) ng/mL. For 193 patients (86.5 %) it was the first IVF/ICSI cycle and for 30 (13.5 %) the second. The algorithm was used for the calculation of the starting dose for 88.3 % of the patients. The mean daily starting dose of follitropin delta was 11.4 ± 4.1mcg for the whole analyzable population and 14.4 ± 5.2 mcg for the sub-group of 26 patients dosed without the algorithm. The mean duration of stimulation with follitropin delta was 10.8 ± 5.2 days. The mean total dose of follitropin delta administered was 122.2 ± 80.0 mcg. An antagonist protocol was used in 90.3 % of patients. The mean ± SD number of oocytes retrieved among patients that started stimulation was 11.3 ± 6.8 and 46.1 % of patients achieved the targeted response of the algorithm of 8-14 oocytes retrieved. A fresh transfer was performed for 77.6 % of patients; the mean ± SD number of embryos transferred was 1.3 ± 0.5. The implantation rate was 36.0 %. Per started cycle, clinical pregnancy was reported in 35.0 % of the patients and ongoing pregnancy in 29.6 %. In total, 5 patients (2.2 %) reported an event of OHSS.Conclusion: Clinical results as collected in routine clinical practice are promising, showing a favorable effectiveness-safety profile of follitropin delta for a very varied patient population (including anovulatory PCOS, very poor responders, or non-IVF naïve patients). These real-world data complement results from clinical trials and provide useful information for usual clinical practice within a heterogeneous population group