Noninvasive Implantation Potential vs Morphology-Based Selection in IVF Single Blastocyst Transfer

Summary

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.

Conditions

• Advanced Age
• Recurrent Pregnancy Loss(RPL)
• Infertility (IVF Patients)
• Sequence Analysis
• Embryo Quality

Interventions

OTHER

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.

OTHER

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.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

43 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2030-04-30

Completion

2032-03-31

Countries

• China

Study Locations