P-576 Pharmacokinetic and pharmacodynamic modelling to explore dosing regimens of corifollitropin alfa for ovarian stimulation without the need for additional daily recFSH injections
Notice bibliographique
Résumé
Abstract Study question Can ovarian stimulation in IVF patients be realized with one or two corifollitropin alfa (CFA) injections only? Summary answer For 94% of IVF patients, ovarian stimulation can be safely completed with a maximum of two CFA injections What is known already A single dose CFA replaces the first week of stimulation with daily recFSH, providing ovarian stimulation similar to daily 300 IU recFSH. Pharmacokinetic and pharmacodynamic (PK/PD) modelling has shown that a threshold serum FSH concentration of 1.1 ng/ml (∼ 6.72 IU/L) is required to maintain multiple follicular development, and that such FSH concentrations are maintained for 7 days following single injection. From day 8 onwards, most patients require daily recFSH injections to maintain serum FSH above threshold to complete the follicular growth. Patients requiring profound stimulation, e.g. prior to ‘freeze-all’, would benefit most from CFA only treatment, requiring less injections. Study design, size, duration This was a retrospective analysis using individual patient data from 4 large CFA trials, including totally 2397 IVF patients receiving a single injection of CFA followed by daily follitropin beta injections from day 8 of stimulation until triggering. Participants/materials, setting, methods A PK model developed for CFA was used to predict serum concentrations following different dosing regimens of CFA only. Clinical trial data from 2397 patients was used to estimate the distribution of the required length of stimulation and to evaluate the impact of different dosing regimens on the serum FSH concentrations up to the day of triggering. Main results and the role of chance At stimulation day 8, 21% of patients did not require additional FSH, whereas 25%, 27%, 14%, and 7% needed 1, 2, 3 or 4 days additional stimulation days to complete the cycle. Only 6% required more than 4 days additional stimulation. Patients below 60 kg remained longer above the threshold and additional dosing could have been delayed to stimulation day 9-11 depending on the initial dose (100 or 150 mg). In a 70 kg woman, daily doses of 7 mg CFA would be sufficient to maintain trough concentrations of FSH above the threshold, and a single dose of 15 and 30 mg on day 8 would sustain stimulation for another 2 and 4 days, respectively. A single dose of 30 mg on day 8 would increase FSH concentrations from 7 IU/L to a maximal level of approximately 12 IU/L, a fluctuation that is unlikely to recruit new small follicles during the late follicular phase. It is therefore suggested that patients can be safely treated with a second dose of 30 mg CFA on day 8 of stimulation, without risk of overdosing when receiving GnRH agonist triggering, and that 94% of patients will not need more than two doses. Limitations, reasons for caution The theoretical dosing regimens build upon this retrospective analysis and modelling needs to be validated in a clinical study to confirm that one additional dose of CFA is able to complete ovarian stimulation efficiently. Wider implications of the findings IVF patients planned to have ‘freeze-all’ following GnRH agonist triggering may be treated conveniently with one or max two injections of CFA for ovarian stimulation. Trial registration number not applicable
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».