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

NCT07461077 | Not Yet Recruiting DMC

• 1 other identifier: SYS-5010-202609
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

NICS; AI; single embryo transfer; live birth rate; Embryo quality

Outcome Measures

Primary Outcomes (1)

• Live birth rate of the first frozen embryo transfer

  live birth: number of deliveries resulting in at least one live-born infant per embryo transfer cycle Live birth rate of the first frozen embryo transfer = (No. of deliveries with live-born infant(s) after the last embryo transfer / No. of randomized patients) × 100%

  At delivery (following the first frozen embryo transfer)

Secondary Outcomes (7)

• Clinical pregnancy rate of the first frozen embryo transfer

  4 weeks after the first frozen embryo transfer

• Early miscarriage rate of the first frozen embryo transfer

  From clinical pregnancy confirmation to 12 gestational weeks (following the first frozen embryo transfer)

• Ongoing pregnancy rate of the first frozen embryo transfer

  At 12 gestational weeks (following the first frozen embryo transfer)

• Cumulative clinical pregnancy rate

  From the first single-blastocyst transfer; clinical pregnancy assessed at 4 weeks after each transfer; up to three transfers within 12 months after randomization.

• Cumulative early miscarriage rate

  From the first single-blastocyst transfer; follow-up through 12 gestational weeks for each pregnancy achieved (max 3 transfers within 12 months after randomization).

Study Arms (2)

NICS-AI group

EXPERIMENTAL

Other: NICS-AI

Morphology group

ACTIVE COMPARATOR

Other: Morphology group

Interventions

NICS-AI OTHER

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.

NICS-AI group

Morphology group OTHER

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.

Morphology group

Eligibility Criteria

• Age: 20 Years - 43 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Conventional IVF insemination;
• Meeting either of the following:
• Advanced maternal age: female age 35-43 years;
• Recurrent miscarriage: ≥2 spontaneous pregnancy losses (\<28 gestational weeks), including biochemical pregnancy (hCG \>25 IU/L) ;
• Willingness to culture all Day 3 embryos to the blastocyst stage in the fresh cycle, or to culture ≥6 embryos (with at least one embryo ≥7 cells), and to cryopreserve all blastocysts as single-blastocyst vitrification;
• Willingness to undergo frozen-thawed single-blastocyst transfer;
• At least two blastocysts formed on Day 5/Day 6 from 2PN fertilization, with morphological grading ≥4BC/4CB;
• Provision of written informed consent.

You may not qualify if:

• Any use of intracytoplasmic sperm injection-based fertilization, including but not limited to ICSI, TESA, and PGT-related cycles;
• Known monogenic disorders or chromosomal abnormalities at enrollment;
• Patients who use donated eggs to achieve pregnancy;
• Definite conditions affecting uterine cavity anatomy or endometrial receptivity, such as untreated uterine malformations (e.g., septate uterus, unicornuate uterus, didelphys uterus) or untreated hydrosalpinx;
• Contraindications to pregnancy or to assisted reproductive technology;
• Any other condition deemed by the investigators to make the participant unsuitable for this study.

Sponsors & Collaborators

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

Study Sites (1)

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

Guangzhou, Guangdong, 510120, China

Location

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Central Study Contacts

Ping Yuan, Doctor

CONTACT

+8613751885713; kekeyp1983@163.com

Haijing Zhao

CONTACT

+8615217456163; zhaohj0502@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 10, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): March 31, 2032
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)