HELIOS Advanced: Human Embryo Illumination to Enhance Development (HELIOS-A)

November 5, 2026 updated by: Samuel Zev Williams, Columbia University

HELIOS-Advanced: A Prospective, Staged Dose-Escalation Study of Photobiomodulation to Improve Embryo Development in In Vitro Fertilization

As women get older, the "power plants" of the cells (called mitochondria) don't work as well. This makes it harder for eggs and embryos to develop normally. One possible way to help is with a gentle light treatment called photobiomodulation (PBM). This uses a special type of red light that boosts energy production in cells and helps them stay healthy. This study will test whether adding this light treatment during in vitro fertilization (IVF) can improve embryo growth and pregnancy outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Embryo development is highly energy-dependent, and impaired mitochondrial function is a well-established hallmark of reproductive aging. As women age, reactive oxygen species (ROS) accumulate and cause mitochondrial DNA (mtDNA) damage, leading to reduced oxidative phosphorylation, ATP (Adenosine 5'-triphosphate) depletion, and developmental arrest of embryos. Enhancing mitochondrial function represents a promising strategy to improve embryo quality, particularly in women of advanced maternal age.

Photobiomodulation (PBM), also known as low-level light therapy (LLLT), involves the application of low-intensity red or near-infrared (NIR) light to modulate mitochondrial activity. NIR light specifically activates cytochrome c oxidase, leading to increased ATP production, reduced oxidative stress, and improved cellular resilience. Numerous preclinical studies, including isolated mitochondria, cell cultures, and in vivo animal models, have confirmed the safety and efficacy of NIR light in restoring mitochondrial function without inducing DNA damage or chromosomal abnormalities.

The investigators previously conducted IRB-approved laboratory studies using mouse and donated human embryos, demonstrating that brief exposure to PBM improved blastocyst formation without adversely affecting chromosomal status.

The current study builds upon this foundational work to evaluate the clinical impact of PBM at the oocyte stage. In a randomized, blinded, sibling-embryo design, the investigators will test whether PBM improves fertilization rates, blastocyst formation, embryo quality, and pregnancy outcomes in participants undergoing IVF or ICSI (Intracytoplasmic sperm injection) with PGT-A (preimplantation genetic testing for aneuploidy) using their autologous oocytes.

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10019
        • Recruiting
        • Columbia University Fertility Center
        • Principal Investigator:
          • Samuel Z Williams, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 48 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female age between 18-48 years at the time of the IVF/ICSI cycle
  • Undergoing blastocyst culture
  • Using own oocytes
  • Has at least two cleavage stage embryos available for randomization on Day 3 of embryo development
  • Consenting to embryo level randomization
  • Plan to transfer euploid embryo within 6 months

Exclusion Criteria:

  • Use of donor oocytes or gestational carrier
  • Concurrent experimental laboratory inventions outside of protocol
  • Refusal of randomization or request for non-standard handling

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No photobiomodulation

Participants will receive the same treatment (IVF/ICSI cycles with PGT-A). Participant's resultant cleavage stage embryos will be randomized to not receive PBM.
Experimental: Photobiomodulation

Participants will receive the same treatment (IVF/ICSI cycles with PGT-A). Participant's resultant cleavage stage embryos will be randomized to receive PBM.
Other: Photobiomodulation

Photobiomodulation (PBM): also known as low-level light therapy (LLLT), involves the application of low-intensity red or near-infrared (NIR) light to modulate mitochondrial activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of usable blastocysts
Time Frame: Seven days post egg retrieval

Usable blastocysts are defined as blastocysts that can be biopsied and frozen on Day 5, 6, or 7 of development for PGT-A (pre-implantation genetic testing for aneuploidy). The study will calculate the usable blastocyst rate per oocyte retrieved defined as the number of usable blastocysts per cleavage stage embryo on Day 3.
Seven days post egg retrieval

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to 2-cell stage
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the 2-cell stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to 3-cell stage
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the 3-cell stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to 6-cell stage
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the 6-cell stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to 8-cell stage
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the 8-cell stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to morula
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the morula stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to start of blastulation
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to start blastulation from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to blastocyst
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the blastocyst stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Time to hatching blastocyst
Time Frame: Up to seven days post egg retrieval

Time (hours) for embryo to reach the hatching blastocyst stage from insemination/ICSI as assessed by embryology using time-lapse imaging.
Up to seven days post egg retrieval
Number of good quality blastocysts as defined by Gardner grading system
Time Frame: Up to seven days post egg retrieval

Final blastocyst quality at the time of cryopreservation (Day 5,6, or 7) will be assessed using the Gardner grading system, which consists of three parameters: expansion and hatching status (graded 1-6), inner cell mass (graded A-D), and trophectoderm (graded A-D). A good quality blastocyst will be defined as a blastocyst of grade 3BB or higher.
Up to seven days post egg retrieval
Euploidy Rate
Time Frame: Within 30 days post egg retrieval

The chromosomal ploidy status of cryopreserved blastocysts is assessed by the presence of two copies of each autosome and the expected complement of sex chromosomes. The euploidy rate is defined as the number of cryopreserved blastocysts that have the correct number of chromosomes divided by the total number of cryopreserved blastocysts.
Within 30 days post egg retrieval
Proportion of Embryo Selected for Transfer
Time Frame: Within 1 year post egg retrieval

In cases with no stated embryo sex preference, the proportion of cycles in which the embryo selected for transfer is from the PBM-treated group versus the control group will be reported.
Within 1 year post egg retrieval
Implantation Rate
Time Frame: Within 1 year post egg retrieval

Implantation rate is defined as the number of cycles with positive beta hCG (human chorionic gonadotropin) nine days or more post frozen embryo transfer divided by the total number of frozen embryo transfer cycles.
Within 1 year post egg retrieval
Clinical pregnancy rate
Time Frame: Within 1 year post egg retrieval

Clinical pregnancy rate is defined as the number of cycles with the presence of a gestational sac visualized on transvaginal ultrasound divided by the total number of frozen embryo transfer cycles.
Within 1 year post egg retrieval
Miscarriage rate
Time Frame: Within 1 year of egg retrieval

Miscarriage rate is defined as the number of cycles with clinical pregnancy losses divided by the number of cycles that had positive hCGs post frozen embryo transfer.
Within 1 year of egg retrieval
Live birth rate
Time Frame: Up to 2 years post egg retrieval

Live birth rate is defined as the number of cycles with a live born infant after 24 weeks gestation divided by total number of frozen embryo transfer cycles.
Up to 2 years post egg retrieval
Gestational Age at Delivery
Time Frame: Up to 2 years post egg retrieval

Total number of completed weeks and days of pregnancy, calculated using frozen embryo transfer date.
Up to 2 years post egg retrieval
Birthweight
Time Frame: Up to 2 years post egg retrieval

The weight of the baby at birth in grams
Up to 2 years post egg retrieval

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Investigators

  • Principal Investigator: Samuel Zev Williams, MD/PhD, Columbia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

February 13, 2026

First Submitted That Met QC Criteria

February 13, 2026

First Posted (Actual)

February 20, 2026

Study Record Updates

Last Update Posted (Actual)

November 9, 2026

Last Update Submitted That Met QC Criteria

November 5, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACYY1279

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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