NICS-AI: 1. Collection of spent blastocyst culture medium and embryo cryopreservation: after thorough removal of granulosa cells from the zona pellucida, Day-4 embryos are washed and the medium is refreshed. When the embryo reaches an expanded stage-4 blastocyst (about 180 um), pre-freeze collapse is performed and the culture medium is collected. Samples are stored at -20 ℃ pending testing; blastocysts are vitrified. 2. Testing and scoring: samples undergo whole-genome amplification, library preparation, and sequencing. An AI-assisted model integrates sequencing results (including CNV resolution, mosaicism, euploidy/sex chromosome status, number of abnormal chromosomes), morphology grade, and day of blastulation to generate a composite implantation potential score (reported as \<10 or 10-66). 3. Frozen-thawed single blastocyst transfer: embryos are prioritized for transfer from highest to lowest composite score. If scores are identical, embryos are prioritized by cryopreservation order.
Morphology group: 1. When the embryo reaches an expanded stage-4 blastocyst (about 180 um), pre-freeze collapse is performed and the culture medium is collected. Samples are stored at -20 C pending testing; blastocysts are vitrified. 2. Single-blastocyst transfer in frozen-thawed cycles, determined solely by the day of blastulation and morphological grading: i) Day 5 blastocysts are prioritized over Day 6 blastocysts (Day 5 \> Day 6); ii) For blastocysts formed on the same day, prioritization follows this order: 6AA \> 6BA \> 6AB \> 5AA \> 5BA \> 5AB \> 4AA \> 4BA \> 4AB \> 6BB \> 5BB \> 4BB \> 6CA \> 5CA \> 6CB \> 5CB \> 4CA \> 4CB \> 6AC \> 5AC \> 6BC \> 5BC \> 4AC \> 4BC; iii) If both the day of blastulation and the morphological grade are identical, embryos are transferred according to the order of cryopreservation (e.g., based on the cryo-straw identification number). 3. For all enrolled patients, the study-designated (enrolled) blastocysts are prioritized for transfer.
Background: Morphology-based embryo selection cannot detect aneuploidy, which is common in advanced maternal age and recurrent pregnancy loss. NICS-AI combines non-invasive chromosome screening (NICS) of cell-free DNA from spent blastocyst culture medium with AI integration of developmental day and morphology to improve embryo ranking.
Methods: This multicenter, single-blind, parallel randomized controlled trial will include 520 participants. Participants undergoing conventional IVF will be eligible if they meet either (i) female age 35-43 years or (ii) recurrent miscarriage (≥2 losses \<28 gestational weeks, including biochemical pregnancy with serum hCG \>25 IU/L). They must consent to blastocyst culture/vitrification and frozen-thawed single blastocyst transfer (SBT), and have ≥2 Day-5/Day-6, 2PN-derived blastocysts with morphology grade ≥4BC/4CB at randomization. Key exclusions include any ICSI-based fertilization or PGT-related procedures, known genetic disease meeting PGT indications, donor oocytes, untreated uterine anomalies/hydrosalpinx, or contraindications to pregnancy/ART.
Randomization/interventions: Participants will be randomized 1:1 to NICS-AI-guided selection or morphology-based selection. In the NICS-AI arm, culture-medium DNA is tested and an AI-derived composite implantation score ranks embryos; controls use morphology alone (tie-break by cryopreservation order).
Outcomes/analysis: The primary endpoint is live birth after the first SBT (delivery with ≥1 live-born infant per transfer cycle, per randomized participant). Secondary endpoints include first clinical pregnancy, early miscarriage (\<12 weeks, excluding biochemical pregnancy), ongoing pregnancy to 12 weeks, and cumulative pregnancy/live birth outcomes within 1 year (≤3 SBTs from one retrieval). Safety includes fetal malformations and neonatal outcomes through 1 year postpartum.
| Facility | City | Region | Status |
|---|---|---|---|
| Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Guangzhou | Guangdong |
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07461077 on ClinicalTrials.gov ↗ ← All trials in China