Day-3 vs Day-5 Assisted Hatching: Impact on Blastocyst Morphology and PGT-A Outcomes

NCT ID: NCT07154875

Last Updated: 2025-09-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-14

Study Completion Date

2028-06-14

Brief Summary

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This randomized controlled trial evaluates the effect of assisted hatching (AH) timing on embryo development and genetic outcomes in in vitro fertilization (IVF) cycles with preimplantation genetic testing for aneuploidy (PGT-A). Eligible patients undergoing IVF with PGT-A will have embryos randomized to receive assisted hatching either on Day-3 or Day-5 of culture, prior to trophectoderm biopsy. The primary outcome is the rate of aneuploid blastocysts. Secondary outcomes include blastocyst morphology, expansion stage, and the correlation between morphology and genetic results. The study aims to determine whether earlier or later assisted hatching affects embryo viability and the accuracy of genetic testing. The trial will provide evidence to optimize laboratory protocols in IVF centers.

Detailed Description

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This prospective randomized controlled trial compares two standardized laboratory procedures of assisted hatching (AH) timing in IVF cycles undergoing PGT-A. In Arm A, AH will be performed on Day-3 embryos; in Arm B, AH will be performed on Day-5 blastocysts prior to trophectoderm biopsy. A total of approximately 200 IVF cycles, involving around 650 embryos, will be included. Randomization will be conducted using block randomization. The primary outcome is the proportion of aneuploid blastocysts identified by next-generation sequencing (NGS). Secondary outcomes include blastocyst morphology (ICM, TE, expansion), biopsy efficiency, and correlation between morphological parameters and genetic outcomes.

All procedures are part of the routine IVF-PGT workflow, and no additional risks to patients are introduced beyond standard care. The trial has been approved by the Institutional Review Board of 16A Ha Dong General Hospital.

Conditions

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Infertility; In Vitro Fertilization; Embryo Development

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Embryos randomized to receive assisted hatching on Day-3 (Arm A) or Day-5 (Arm B) prior to trophectoderm biopsy.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The PGT-A analysts evaluating the NGS results were blinded to the assisted hatching timing.

Study Groups

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Day-3 Assisted Hatching

Embryos undergo laser-assisted zona drilling on Day-3. Embryos are then cultured to Day-5 and biopsied for PGT-A.

Group Type EXPERIMENTAL

Assisted Hatching

Intervention Type PROCEDURE

Laser-assisted zona drilling performed either on Day-3 or Day-5 of culture, depending on randomization arm.

Day-5 Assisted Hatching

Embryos are cultured without zona drilling until Day-5. Laser-assisted hatching is performed immediately before trophectoderm biopsy for PGT-A.

Group Type EXPERIMENTAL

Assisted Hatching

Intervention Type PROCEDURE

Laser-assisted zona drilling performed either on Day-3 or Day-5 of culture, depending on randomization arm.

Interventions

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Assisted Hatching

Laser-assisted zona drilling performed either on Day-3 or Day-5 of culture, depending on randomization arm.

Intervention Type PROCEDURE

Other Intervention Names

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Laser-assisted hatching LAH Zona drilling AH

Eligibility Criteria

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Inclusion Criteria

* IVF cycles with PGT-A
* Oocyte age 20-45 years (donor cycles: donor's age)
* AMH 1-10 ng/mL within 12 months
* AFC ≥5 follicles (2-9 mm, both ovaries, day 2-5)
* Controlled ovarian stimulation: antagonist or PPOS protocols
* Stratified analysis by age (\<30, 30-34, 35-39, ≥40)
* Sperm source: ejaculated samples prepared by density-gradient or swim-up
* No surgical sperm retrieval
* No advanced sperm selection (IMSI, PICSI, MACS)

Exclusion Criteria

* History of ≥3 failed IVF cycles or ≥3 consecutive miscarriages
* Indication for PGT-M or PGT-SR (monogenic disorders, translocations)
* Severe medical/autoimmune conditions affecting oocytes/embryos (e.g. uncontrolled diabetes, active lupus)
* No MII oocytes available for ICSI
* Embryos not eligible for biopsy per SOP (early zona hatching, degeneration, poor expansion)
* Sperm from surgical retrieval or advanced sperm selection (IMSI, PICSI, MACS)
* PCOS diagnosed by Rotterdam criteria (≥2/3 features)
Minimum Eligible Age

20 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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16A Ha Dong General Hospital

OTHER

Sponsor Role collaborator

Hoang Minh Ngan

OTHER

Sponsor Role lead

Responsible Party

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Hoang Minh Ngan

Principal Investigator, Embryologist, Head of IVF Laboratory

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ngan M Hoang, MSc

Role: PRINCIPAL_INVESTIGATOR

Center for Reproductive Support, 16A Ha Dong General Hospital

Tao D Nguyen, MD, PhD, Professor

Role: STUDY_CHAIR

Center for Reproductive Support, 16A Ha Dong General Hospital

Locations

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Center for Reproductive Support, 16A Ha Dong General Hospital

Hanoi, Hanoi, Vietnam

Site Status RECRUITING

Countries

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Vietnam

Central Contacts

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HOANG M NGAN, MSc

Role: CONTACT

0936749290

Facility Contacts

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Ngan M Hoang, Principal Investigator

Role: primary

0936749290

References

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ESHRE Working Group on Recurrent Implantation Failure; Cimadomo D, de Los Santos MJ, Griesinger G, Lainas G, Le Clef N, McLernon DJ, Montjean D, Toth B, Vermeulen N, Macklon N. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open. 2023 Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023. eCollection 2023.

Reference Type BACKGROUND
PMID: 37332387 (View on PubMed)

McArthur SJ, Leigh D, Marshall JT, de Boer KA, Jansen RP. Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts. Fertil Steril. 2005 Dec;84(6):1628-36. doi: 10.1016/j.fertnstert.2005.05.063.

Reference Type BACKGROUND
PMID: 16359956 (View on PubMed)

Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, Nagy ZP, Ubaldi FM. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014 Jun;29(6):1173-81. doi: 10.1093/humrep/deu033. Epub 2014 Feb 26.

Reference Type BACKGROUND
PMID: 24578475 (View on PubMed)

Related Links

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https://benhvien16a.com/

Official website of 16A Ha Dong General Hospital - Center for Reproductive Support

Other Identifiers

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16A-IRB-2025

Identifier Type: OTHER

Identifier Source: secondary_id

AH-PGTA-2025

Identifier Type: -

Identifier Source: org_study_id

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