Personalizing the first dose of FSH for IVF/ICSI patients through machine learning: a non-inferiority study protocol for a multi-center randomized controlled trial.

Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2006-

Follicle Stimulating Hormone*/adverse effects ; Ovarian Hyperstimulation Syndrome*/etiology ; Ovarian Hyperstimulation Syndrome*/prevention & control; Male ; Pregnancy ; Humans ; Female ; Adult ; Sperm Injections, Intracytoplasmic/methods ; Prospective Studies ; Ovulation Induction/adverse effects ; Ovulation Induction/methods ; Semen ; Fertilization in Vitro/methods ; Pregnancy Rate ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Background: Adequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years.
Methods: This is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer.
Discussion: To our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application.
Trial Registration: ClinicalTrials.gov, NCT05948293 . Registered on 14 July 2023.
(© 2024. The Author(s).)

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DI-2019-24 Agència de Gestió d'Ajuts Universitaris i de Recerca; PID2019-104156GB-I00 Ministerio de Ciencia e Innovación

Keywords: Artificial intelligence; Controlled ovarian stimulation; Decision support system; FSH; IVF; Machine learning

ClinicalTrials.gov NCT05948293

9002-68-0 (Follicle Stimulating Hormone)

Date Created: 20240111 Date Completed: 20240115 Latest Revision: 20240115

20240115

PMC10782678

10.1186/s13063-024-07907-2

38212837