Alpha-Lipoic Acid Supplementation and IVF Outcomes in Women of Advanced Maternal Age

July 3, 2026 updated by: Li-Te Lin, Kaohsiung Veterans General Hospital.

Effects of Alpha-Lipoic Acid Supplementation on Oocyte Quality, Cumulus Cell Mitochondrial Function, and In Vitro Fertilization Outcomes in Infertile Women of Advanced Maternal Age: A Prospective Cohort Study

Female fertility declines with advancing age, largely because of deteriorating oocyte quality driven by mitochondrial dysfunction and oxidative stress within the ovarian microenvironment. Alpha-lipoic acid (ALA) is a potent antioxidant that crosses cell and mitochondrial membranes, regenerates other antioxidants (vitamin C, vitamin E, glutathione, coenzyme Q10), and supports mitochondrial respiratory chain activity and ATP production. This prospective study will enroll 60 infertile women aged 35-45 years undergoing in vitro fertilization (IVF) treatment. Thirty participants will receive oral ALA 600 mg/day for two months before their IVF cycle, and thirty will proceed directly to IVF without supplementation. The study will compare oocyte and embryo quality, cumulus cell mitochondrial function and metabolic gene expression, and clinical pregnancy and live birth rates between the two groups.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Oocyte quality declines markedly after age 35, with chromosomal abnormality rates rising from approximately 25% at age 35 to over 50% at age 40, paralleling a fall in IVF success rates from roughly 35-45% under age 35 to 5-15% after age 40. The mechanistic core of this decline is mitochondrial dysfunction: mature oocytes contain 100,000-600,000 mitochondria to meet exceptionally high energy demands for maturation, fertilization, and early embryogenesis, and oocyte ATP content correlates with fertilization rate, blastocyst formation, and implantation. With aging, oocyte mitochondria accumulate mtDNA mutations, show reduced respiratory chain activity and ATP output, generate excess reactive oxygen species (ROS), and exhibit lower membrane potential - a self-reinforcing cycle of oxidative damage and bioenergetic failure that disrupts meiotic spindle formation and chromosome segregation.

ALA is a disulfide-containing fatty acid that exists in interconvertible oxidized (ALA) and reduced (dihydrolipoic acid) forms. Its dual hydrophilic-lipophilic structure allows it to penetrate cell and mitochondrial membranes and scavenge superoxide, hydroxyl, and peroxide radicals directly, while also regenerating other components of the antioxidant network and chelating transition metals (iron, copper) that drive Fenton-reaction oxidative damage. As a cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, ALA participates directly in the TCA cycle, stabilizes mitochondrial membrane potential, enhances electron transport chain activity, reduces electron leakage and ROS generation, and upregulates PGC-1α-driven mitochondrial biogenesis. Animal studies (Tarín et al.; Liu et al.; Ben-Meir et al.) have shown that ALA supplementation in aged female mice improves oocyte mitochondrial distribution, lowers ROS, raises ATP content and membrane potential, reduces aneuploidy, and increases cleavage and blastocyst rates. In humans, evidence is currently limited to PCOS cohorts - a randomized trial by Genazzani et al. (600 mg/day, 6 months) showed improved insulin sensitivity, lower androgen levels, and higher ovulation rates - while prospective trials of ALA in IVF patients of advanced maternal age are lacking.

This study addresses that gap. Sixty women aged 35-45 years planning IVF will be assigned to an ALA group (oral ALA 600 mg/day for 2 months before the IVF cycle) or a control group (standard IVF without supplementation) in a 1:1 ratio. Cumulus-oocyte complexes will be collected at retrieval; cumulus cells will be isolated by hyaluronidase digestion and mechanical separation, then assessed for mitochondrial ROS (DCFDA, MitoSOX), mitochondrial mass/membrane potential (MitoTracker Green), and ATP content (fluorescent ATP live-cell dye) by fluorescence microscopy and flow cytometry, alongside qPCR profiling of mitochondria-related metabolic gene expression (normalized to RNU6-1). Clinical endpoints - oocyte and embryo quality, clinical pregnancy rate, and live birth rate - will be compared between groups to determine whether ALA supplementation translates improved cumulus cell bioenergetics into better IVF outcomes in this age group.

Study Type

Interventional

Enrollment (Estimated)

60

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

  • Taiwan
      • Kaohsiung City, Taiwan, 813
        • Recruiting
        • Kaohsiung Veterans General Hospital
        • Principal Investigator:
          • Li-Te Lin
        • 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

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 35-45 years
  • BMI 18-35 kg/m²
  • Planning to undergo IVF treatment using own oocytes

Exclusion Criteria:

  • Primary ovarian insufficiency
  • Azoospermia or severe male-factor infertility in the partner
  • Congenital uterine anomaly
  • Severe intrauterine adhesion
  • Known chromosomal anomaly in either partner
  • Malignancy
  • Recipient of donor oocytes
  • Known hypersensitivity/allergy to alpha-lipoic acid

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alpha-Lipoic Acid + IVF
Participants receive oral alpha-lipoic acid 600 mg/day for 2 months, followed by a standard controlled ovarian stimulation IVF cycle
Dietary supplement: Alpha-Lipoic Acid (ALA)
Oral Alpha-Lipoic Acid 600 mg/day for 2 months prior to IVF cycle initiation
No Intervention: Standard IVF (Control)
Participants proceed directly to a standard controlled ovarian stimulation IVF cycle without alpha-lipoic acid or any other antioxidant supplementation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Embryo quality
Time Frame: through study completion, an average of 1 year
proportion of top-grade embryos (Day 3) or blastocysts (Day 5) per standard grading criteria
through study completion, an average of 1 year
Cumulus cell mitochondrial function
Time Frame: through study completion, an average of 1 year
ATP content, mitochondrial membrane potential, ROS level, and mitochondrial DNA copy number
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: through study completion, an average of 1 year
presence of a gestational sac with fetal heartbeat on transvaginal ultrasound at 6-7 weeks' gestation
through study completion, an average of 1 year
Live birth rate
Time Frame: through study completion, an average of 1 year
delivery of a live infant after 24 weeks' gestation
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Kaohsiung Veterans General Hospital.

Investigators

  • Study Director: Kuan-Hao Tsui, Kaohsiung Veterans General Hospital.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

June 11, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

June 29, 2026

First Submitted That Met QC Criteria

June 29, 2026

First Posted (Actual)

July 6, 2026

Study Record Updates

Last Update Posted (Actual)

July 7, 2026

Last Update Submitted That Met QC Criteria

July 3, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KSVGH26-CT3-49

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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