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Female Infertility Due to Diminished Ovarian ReserveNCT07685431

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

A study testing Alpha-Lipoic Acid (ALA) in people with Female Infertility Due to Diminished Ovarian Reserve, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Female fertility declines with advancing age, largely because of deteriorating oocyte quality driven by mitochondrial dysfunction and oxidative stress within the ovarian microenvironment. Read more about this study

Who is it for?
Ages 35 to 45 years, women only
What is being tested?
Alpha-Lipoic Acid (ALA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteTaiwan
Study dates
11 Jun 2026to 30 Jun 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 45 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Taiwan1 site, 1 recruiting
  • Kaohsiung Veterans General Hospital

    Kaohsiung City, 813

    Li-Te Lin, +886-7-3464027, litelin1982@gmail.com

    Li-Te Lin

    Recruiting

Other trials in Taiwan

About this study

Official title: 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.

Read the 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.

Being tested
Alpha-Lipoic Acid (ALA)
Keywords
Alpha-lipoic acid, In vitro fertilization, Advanced maternal age, Oocyte quality, Mitochondrial function, Cumulus cells

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alpha-Lipoic Acid (ALA)Dietary supplement

    Oral Alpha-Lipoic Acid 600 mg/day for 2 months prior to IVF cycle initiation

Study groups in NCT07685431
Study groupRoleWhat they receive
Alpha-Lipoic Acid + IVFExperimentalParticipants receive oral alpha-lipoic acid 600 mg/day for 2 months, followed by a standard controlled ovarian stimulation IVF cycle
Receives: Dietary Supplement: Alpha-Lipoic Acid (ALA)
Standard IVF (Control)No interventionParticipants proceed directly to a standard controlled ovarian stimulation IVF cycle without alpha-lipoic acid or any other antioxidant supplementation.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Embryo quality

    proportion of top-grade embryos (Day 3) or blastocysts (Day 5) per standard grading criteria

    Measured: through study completion, an average of 1 year

  2. Cumulus cell mitochondrial function

    ATP content, mitochondrial membrane potential, ROS level, and mitochondrial DNA copy number

    Measured: through study completion, an average of 1 year

Secondary outcomes (2)
  1. Clinical pregnancy rate

    presence of a gestational sac with fetal heartbeat on transvaginal ultrasound at 6-7 weeks' gestation

    Measured: through study completion, an average of 1 year

  2. Live birth rate

    delivery of a live infant after 24 weeks' gestation

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2026
  2. Study start11 Jun 2026
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07685431
Sponsor's protocol ID
KSVGH26-CT3-49
Status last verified
Jul 2026
First submitted
29 Jun 2026
Last updated
7 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Erdem Guzel E, Kaya N, Tektemur A, Ulker N, Yardimci A, Akkoc RF, Canpolat S, Ozan IE. Chronic effects of maternal tobacco-smoke exposure and/or alpha-lipoic acid treatment on reproductive parameters in female rat offspring. Syst Biol Reprod Med. 2020 Dec;66(6):387-399. doi: 10.1080/19396368.2020.1815248. Epub 2020 Sep 20.

    PubMed 32951465
  • Abu-Zaid A, Baradwan S, Bukhari IA, Alyousef A, Abuzaid M, Saleh SAK, Adly HM, Alomar O, Al-Badawi IA. The effect of alpha-lipoic acid supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in individuals with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials. Obstet Gynecol Sci. 2024 Jan;67(1):17-29. doi: 10.5468/ogs.23206. Epub 2023 Dec 4.

    PubMed 38044616
  • Rago R, Marcucci I, Leto G, Caponecchia L, Salacone P, Bonanni P, Fiori C, Sorrenti G, Sebastianelli A. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study. J Biol Regul Homeost Agents. 2015 Oct-Dec;29(4):913-23.

    PubMed 26753656
  • Canosa S, Paschero C, Carosso A, Leoncini S, Mercaldo N, Gennarelli G, Benedetto C, Revelli A. Effect of a Combination of Myo-Inositol, Alpha-Lipoic Acid, and Folic Acid on Oocyte Morphology and Embryo Morphokinetics in non-PCOS Overweight/Obese Patients Undergoing IVF: A Pilot, Prospective, Randomized Study. J Clin Med. 2020 Sep 12;9(9):2949. doi: 10.3390/jcm9092949.

    PubMed 32932604
  • Di Nicuolo F, D'Ippolito S, Castellani R, Rossi ED, Masciullo V, Specchia M, Mariani M, Pontecorvi A, Scambia G, Di Simone N. Effect of alpha-lipoic acid and myoinositol on endometrial inflammasome from recurrent pregnancy loss women. Am J Reprod Immunol. 2019 Sep;82(3):e13153. doi: 10.1111/aji.13153. Epub 2019 Jun 19.

    PubMed 31148259
  • Di Tucci C, Galati G, Mattei G, Bonanni V, Capri O, D'Amelio R, Muzii L, Benedetti Panici P. The role of alpha lipoic acid in female and male infertility: a systematic review. Gynecol Endocrinol. 2021 Jun;37(6):497-505. doi: 10.1080/09513590.2020.1843619. Epub 2020 Dec 21.

    PubMed 33345661
  • Guarano A, Capozzi A, Cristodoro M, Di Simone N, Lello S. Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth? Nutrients. 2023 Jul 19;15(14):3209. doi: 10.3390/nu15143209.

    PubMed 37513627
  • Shanaida M, Lysiuk R, Mykhailenko O, Hudz N, Abdulsalam A, Gontova T, Oleshchuk O, Ivankiv Y, Shanaida V, Lytkin D, Bjorklund G. Alpha-lipoic Acid: An Antioxidant with Anti-aging Properties for Disease Therapy. Curr Med Chem. 2025;32(1):23-54. doi: 10.2174/0109298673300496240416114827.

    PubMed 38644711
  • Zhang M, Sun L, Zhang Z, Shentu L, Zhang Y, Li Z, Zhang Y, Zhang Y. Alpha-lipoic acid supplementation restores the meiotic competency and fertilization capacity of porcine oocytes induced by arsenite. Front Cell Dev Biol. 2022 Oct 3;10:943757. doi: 10.3389/fcell.2022.943757. eCollection 2022.

    PubMed 36263016
  • Di Nicuolo F, Castellani R, Ticconi C, Scambia G, Pontecorvi A, Di Simone N. alpha-Lipoic Acid and its Role on Female Reproduction. Curr Protein Pept Sci. 2021 Dec 29;22(11):767-774. doi: 10.2174/1389203722666211029102417.

    PubMed 34719371

Questions about this trial

What is this clinical trial studying?

A study testing Alpha-Lipoic Acid (ALA) in people with Female Infertility Due to Diminished Ovarian Reserve, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Li-Te Lin (+886-7-3464027, litelin1982@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Embryo quality (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07685431, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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