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

Официальное название

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

Обзор

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.

Вмешательства

• Другое 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,
• Другое 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 ord

Первичные конечные точки

• Live birth rate of the first frozen embryo transfer [Срок оценки: At delivery (following the first frozen embryo transfer)]

Вторичные конечные точки (7)

• Clinical pregnancy rate of the first frozen embryo transfer [Срок оценки: 4 weeks after the first frozen embryo transfer]
• Early miscarriage rate of the first frozen embryo transfer [Срок оценки: From clinical pregnancy confirmation to 12 gestational weeks (following the first frozen embryo transfer)]
• Ongoing pregnancy rate of the first frozen embryo transfer [Срок оценки: At 12 gestational weeks (following the first frozen embryo transfer)]
• Cumulative clinical pregnancy rate [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From the first single-blastocyst transfer; assessed at delivery for pregnancies achieved within 12 months after randomization (max 3 transfers).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT07461077 · SYS-5010-202609

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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