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

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

Oocytes need a lot of energy to complete meiosis and fertilize successfully. 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: IVF Outcomes
• Intervention / Treatment: Other: Photobiomodulation

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-oocyte 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

• Study Contact: Name: Samuel Zev Williams, MD, PhD; Phone Number: 646-756-8282; Email: zw2421@cumc.columbia.edu
• Study Contact Backup: Name: Laura C Gemmell, MD, MSc; Phone Number: 646-756-8282; Email: lg3094@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Recruiting
      • Columbia University Fertility Center
      • Contact: Laura C Gemmell, MD, MSc; Phone Number: 646-756-8282; Email: lg3094@cumc.columbia.edu
      • Contact: Stephanie Morgan, MS; Phone Number: 646-756-8282; Email: sm3415@cumc.columbia.edu
      • Principal Investigator: Samuel Z Gemmell, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

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 oocytes available for randomization
• Consenting to oocyte 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

How is the study designed?

Design Details

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

Number of Arms

2

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 oocytes will be randomized to not receive PBM.
Experimental: Photobiomodulation; Participants will receive the same treatment (IVF/ICSI cycles with PGT-A). Participant's resultant oocytes 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	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 divided by the number of oocytes retrieved.	Seven days post egg retrieval

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Embryo Selected for Transfer	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
Clinical pregnancy rate	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
Maturity Rate	For insemination cycles, defined as the number of mature oocytes divided by the total number of oocytes retrieved, assessed the day after the retrieval.	Up to seven days post egg retrieval
Fertilization Rate	The fertilization rate for intracytoplasmic sperm injection (ICSI) cycles is defined as the number of 2PN embryos divided by the number of mature oocytes. For insemination cycles, two fertilization rates will be reported. The first is defined as the number of 2PN embryos divided by the number of cumulus-oocyte-complexes (COC) inseminated. The second is defined as the number of 2PN embryos divided by the number of mature oocytes determined the day after the retrieval.	Up to seven days post egg retrieval
tPNf	Timing of pronuclei fading defined as the time (hours) for both pronuclei to disappear, signaling the end of the 1-cell stage and beginning the first cell division.	Up to seven days post egg retrieval
Time to 2-cell stage	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 (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 (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 (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 (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 (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 (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 (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	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	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
Implantation Rate	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
Miscarriage rate	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	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	Total number of completed weeks and days of pregnancy, calculated using frozen embryo transfer date.	Up to 2 years post egg retrieval
Birthweight	The weight of the baby at birth in grams	Up to 2 years post egg retrieval

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): 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): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Infertility; Fertility; Embryo arrest
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Therapeutics; Laser Therapy; Phototherapy; Low-Level Light Therapy
• 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