Advanced AgeNICSAI-SBT-RCTNCT07461077
Noninvasive Implantation Potential vs Morphology-Based Selection in IVF Single Blastocyst Transfer
A study testing NICS-AI and Morphology group in people with Advanced Age and Recurrent Pregnancy Loss(RPL), run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 43 years, women only
- Conditions the study is for
- Advanced Age, Recurrent Pregnancy Loss(RPL), Infertility (IVF Patients)
- What is being tested?
- NICS-AI and Morphology group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 520 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2026to 31 Mar 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510120
Ping Yuan, Doctor, +8613751885713, kekeyp1983@163.com
About this study
Official title: Clinical Outcomes of Non-invasive Embryo Implantation Potential Assessment Versus Conventional Morphological Selection for Single Blastocyst Transfer Following Conventional IVF: A Multicenter Randomized Controlled Trial
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.
Read more
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
- Being tested
- NICS-AI, Morphology group
- Keywords
- NICS, AI, single embryo transfer, live birth rate, Embryo quality
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NICS-AIOther
- 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.
- 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).
- 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 groupOther
- 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.
- Single-blastocyst transfer in frozen-thawed cycles, determined solely by the day of blastulation and morphological grading:
- 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).
- For all enrolled patients, the study-designated (enrolled) blastocysts are prioritized for transfer.
| Study group | Role | What they receive |
|---|---|---|
| NICS-AI group | Experimental | Not described Receives: Other: NICS-AI |
| Morphology group | Active comparator | Not described Receives: Other: Morphology group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: At delivery (following the first frozen embryo transfer)
Secondary outcomes (7)
Clinical pregnancy rate of the first frozen embryo transfer
clinical pregnancy: ultrasonographic detection of one or more gestational sacs, including intrauterine pregnancy, ectopic pregnancy, and heterotopic pregnancy。 Clinical pregnancy rate of the first frozen embryo transfer = (No. of patients achieving clinical pregnancy of the first frozen embryo transfer / No. of randomized patients) × 100%
Measured: 4 weeks after the first frozen embryo transfer
Early miscarriage rate of the first frozen embryo transfer
early miscarriage: spontaneous pregnancy loss before 12 completed gestational weeks, excluding biochemical pregnancy) Early spontaneous miscarriage rate of the first frozen embryo transfer = (No. of patients with early spontaneous miscarriage <12 weeks of the first frozen embryo transfer / No. of patients with clinical pregnancy) × 100%
Measured: From clinical pregnancy confirmation to 12 gestational weeks (following the first frozen embryo transfer)
Ongoing pregnancy rate of the first frozen embryo transfer
Ongoing pregnancy rate at 12 gestational weeks after the first frozen embryo transfer, Ongoing pregnancy rate of the first frozen embryo transfer = (No. of participants with an ongoing pregnancy at 12 gestational weeks following the first FET / No. of randomized participants) × 100%
Measured: At 12 gestational weeks (following the first frozen embryo transfer)
Cumulative clinical pregnancy rate
Cumulative clinical pregnancy rate: within a single oocyte-retrieval cycle; up to three single-blastocyst transfers within 1 year after randomization; meeting the definition of clinical pregnancy Cumulative clinical pregnancy rate = (No. of patients achieving clinical pregnancy during the transfer period / No. of randomized patients) × 100%
Measured: 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
Cumulative early miscarriage rate: within a single oocyte-retrieval cycle; up to three single-blastocyst transfers within 1 year after randomization; meeting the definition of early miscarriage Cumulative early miscarriage rate = (No. of patients with early spontaneous miscarriage <12 weeks during the transfer period / No. of patients with clinical pregnancy during the transfer period) × 100%
Measured: From the first single-blastocyst transfer; follow-up through 12 gestational weeks for each pregnancy achieved (max 3 transfers within 12 months after randomization).
Cumulative ongoing pregnancy rate
Cumulative ongoing pregnancy rate: within a single oocyte-retrieval cycle; up to three single-blastocyst transfers within 1 year after randomization; ongoing to 12 gestational weeks Cumulative ongoing pregnancy rate = (No. of patients with an ongoing pregnancy during the transfer period / No. of randomized patients) × 100%
Measured: From the first single-blastocyst transfer; follow-up through 12 gestational weeks for each pregnancy achieved (max 3 transfers within 12 months after randomization).
Cumulative live birth rate
Cumulative live birth rate: within a single oocyte-retrieval cycle; up to three single-blastocyst transfers within 1 year after randomization; meeting the definition of live birth Cumulative live birth rate = (No. of live births delivered during the transfer period / No. of randomized patients) × 100%
Measured: From the first single-blastocyst transfer; assessed at delivery for pregnancies achieved within 12 months after randomization (max 3 transfers).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start30 Apr 2026 (estimated)
- Primary completion30 Apr 2030 (estimated)
- Study completion31 Mar 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced AgeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 520 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07461077
- Sponsor's protocol ID
- SYS-5010-202609
- Acronym
- NICSAI-SBT-RCT
- Status last verified
- Mar 2026
- First submitted
- 9 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Outcomes of Non-invasive Embryo Implantation Potential Assessment Versus Conventional Morphological Selection for Single Blastocyst Transfer Following Conventional IVF: A Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07461077
- Acronym / sponsor ID
- NICSAI-SBT-RCT / SYS-5010-202609
- 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
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 520 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 30 Apr 2026 (estimated)
- Primary completion
- 30 Apr 2030 (estimated)
- Study completion
- 31 Mar 2032 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NICS-AI group | Experimental | Other: NICS-AI |
| Morphology group | Active comparator | Other: Morphology group |
Who may qualify
- Ages
- 20 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Conventional IVF insemination;
- Meeting either of the following:
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NICS-AI1. 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 | NICS-AI group |
| Morphology group1. 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. | Other | Morphology group |
Primary outcome
Live birth rate of the first frozen embryo transfer
Time frame: At delivery (following 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%
7 secondary outcomes
Clinical pregnancy rate of the first frozen embryo transfer
Time frame: 4 weeks after the first frozen embryo transfer
Early miscarriage rate of the first frozen embryo transfer
Time frame: From clinical pregnancy confirmation to 12 gestational weeks (following the first frozen embryo transfer)
Ongoing pregnancy rate of the first frozen embryo transfer
Time frame: At 12 gestational weeks (following the first frozen embryo transfer)
Cumulative clinical pregnancy rate
Time frame: 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
Time frame: From the first single-blastocyst transfer; follow-up through 12 gestational weeks for each pregnancy achieved (max 3 transfers within 12 months after randomization).
Cumulative ongoing pregnancy rate
Time frame: From the first single-blastocyst transfer; follow-up through 12 gestational weeks for each pregnancy achieved (max 3 transfers within 12 months after randomization).
Cumulative live birth rate
Time frame: From the first single-blastocyst transfer; assessed at delivery for pregnancies achieved within 12 months after randomization (max 3 transfers).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Advanced Age
RecruitingPhase 2
Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia
Active, not recruitingObservational study
Impact of Glaucoma and Visual Field Loss on Life Space
Primary Open-angle Glaucoma
Not yet recruitingPhase 2
Safety and Efficacy of Gemcitabine, Toripalimab and Dose- Modified Lenvatinib in Elderly Patients With Advanced Biliary Tract Cancer Intolerant to Conventional Chemotherapy
Advanced Biliary Tract Cancer
Not yet recruiting
Multicomponent Exercise and Pain Science Education for Fall Prevention in Older Adults With Chronic Musculoskeletal Pain (MovePainFall)
Chronic Pain, Musculoskeletal Pain
Not yet recruitingObservational study
Prognostic Value of Functional-Nutritional Status in Older Adults With Acute Coronary Syndrome
Acute Coronary Syndromes (ACS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NICS-AI and Morphology group in people with Advanced Age and Recurrent Pregnancy Loss(RPL), run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ping Yuan, Doctor (+8613751885713, kekeyp1983@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate of the first frozen embryo transfer (time frame: At delivery (following the first frozen embryo transfer)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.