Effect of non-invasive preimplantation genetic testing for aneuploidies (ni-PGT) on cumulative ongoing pregnancy in infertile women of advanced maternal age: a multicentre, open-label, randomised controlled trial protocol.

introductionEmbryo aneuploidy increases substantially with maternal age, contributing to implantation failure and miscarriage. Conventional morphological assessment cannot determine euploidy. Non-invasive preimplantation genetic testing (ni-PGT) evaluates cell-free DNA in spent embryo culture medium, potentially improving embryo selection without trophectoderm biopsy. Robust evidence of clinical benefit in women aged 35-42 years remains limited. METHODS AND ANALYSIS: This is a multicentre, open-label, parallel-group randomised controlled trial conducted in three centres in China. Infertile women aged 35-42 years undergoing their first intracytoplasmic sperm injection cycle and having ≥2 good-quality days 5-6 blastocysts (Gardner grade ≥4BC,defined as an expansion grade of at least 4, with an inner cell mass grade of B or better and a trophectoderm grade of C or better) will be randomised 1:1 to ni-PGT-guided embryo selection or conventional morphology-based selection. Randomisation will be stratified by study centre using variable permuted block sizes of 4 and 6 and implemented through a unified centralised randomisation system. After a multicentre set-up period for investigator training and harmonisation of spent culture-medium sampling procedures, during which no participant was enrolled or randomised, recruitment and randomisation commenced on 14 February 2025 at the lead site; additional sites started recruitment after local ethics approval and site initiation. A freeze-all strategy will be applied; frozen-thawed single blastocyst transfer will start from the second menstrual cycle after oocyte retrieval.For the primary endpoint, embryo transfers using embryos from the index retrieval cycle that occur within 12 months after randomisation and within the first three frozen-thawed single embryo transfer attempts will contribute to the cumulative outcome, whichever occurs first. Clinical care will not be restricted beyond this prespecified analysis range. The primary outcome is the cumulative ongoing pregnancy rate within 12 months after randomisation, defined as the proportion of participants achieving at least one ongoing pregnancy (clinical pregnancy continuing to ≥12 weeks' gestation) following a qualifying embryo transfer within the prespecified analysis range. Key secondary outcomes include early miscarriage rate (<12 weeks) in the first transfer cycle, biochemical and clinical pregnancy, time to live birth, number of transfers to live birth, pregnancy/perinatal complications, neonatal birth weight and congenital anomalies. The primary analysis will follow the intention-to-treat principle, comparing groups using relative risks with 95% CIs. A total of 354 participants (177 per group) will be recruited. ETHICS AND DISSEMINATION: The trial will be conducted according to the Declaration of Helsinki. Ethics approval has been obtained from all participating centres before participant recruitment at each site. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2400088283.