IVF Outcomes
Conditions
Keywords
Infertility, Embryo arrest, Fertility
Brief summary
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.
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.
Interventions
OTHERPhotobiomodulation
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.
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
All embryos will be coded and tracked with blinded identifiers. Embryologists and clinicals selecting embryos for transfer will be blinded to treatment group. Selection will follow routine morphological and PGT-A criteria.
Intervention model description
Prospective, sibling-oocyte randomized, double-blind controlled trial. All participants will receive the same treatment (IVF/ICSI cycles with PGT-A). Each participant's resultant oocytes will be randomized into two groups (one group receiving PBM, the other not). The study employs a pre-specified, staged dose-escalation design, beginning with the lowest biologically plausible exposure and escalating conservatively only if predefined criteria for biological activity are not met and no safety concerns are observed. This approach prioritizes risk minimization and ethical stewardship while allowing systematic evaluation of PBM efficacy.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 48 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of usable blastocysts | 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 divided by the number of oocytes retrieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maturity Rate | Up to seven days post egg retrieval | For insemination cycles, defined as the number of mature oocytes divided by the total number of oocytes retrieved, assessed the day after the retrieval. |
| Fertilization Rate | Up to seven days post egg retrieval | 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. |
| tPNf | Up to seven days post egg retrieval | 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. |
| Time to 2-cell stage | 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. |
| Time to 3-cell stage | 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. |
| Time to 6-cell stage | 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. |
| Time to 8-cell stage | 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. |
| Time to morula | 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. |
| Time to start of blastulation | 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. |
| Time to blastocyst | 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. |
| Time to hatching blastocyst | 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. |
| Number of good quality blastocysts as defined by Gardner grading system | 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. |
| Euploidy Rate | 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. |
| Proportion of Embryo Selected for Transfer | 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. |
| Implantation Rate | 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. |
| Clinical pregnancy rate | 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. |
| Miscarriage rate | 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. |
| Live birth rate | 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. |
| Gestational Age at Delivery | Up to 2 years post egg retrieval | Total number of completed weeks and days of pregnancy, calculated using frozen embryo transfer date. |
| Birthweight | Up to 2 years post egg retrieval | The weight of the baby at birth in grams |
Countries
United States
Contacts
CONTACTSamuel Zev Williams, MD, PhD
CONTACTLaura C Gemmell, MD, MSc
PRINCIPAL_INVESTIGATORSamuel Zev Williams, MD/PhD
Columbia University
Outcome results
None listed