Biological Aging Hallmarks-Guided Integrative TCM and Conventional Medicine in Post-Treatment Unexplained Female Infertility

NCT07404969 | Recruiting

• 2 other identifiers: BGX-INFERT-TEL-TCM-202570596.1 INNO-LS
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine whether telomere profiling and other biological aging hallmarks can help identify underlying mechanisms of persistent infertility in women with post-treatment unexplained infertility. The study also evaluates whether a personalized integrative treatment guided by these biomarkers can improve reproductive outcomes. The study includes women aged 25 to 42 years who continue to experience infertility despite appropriate management of identifiable reproductive conditions and repeated attempts with assisted reproductive technologies (ART), such as intrauterine insemination (IUI) or in vitro fertilization (IVF). The main questions this study aims to answer are:

• Can telomere and biological aging hallmarks profiling identify a biological aging phenotype associated with infertility?
• Can an integrative treatment guided by these profiles improve clinical pregnancy outcomes? Participants will:
• Undergo a baseline reproductive evaluation and blood-based assessment of telomeres and aging hallmarks.
• Receive an integrative approach combining Traditional Chinese Medicine (TCM), targeted nutritional support, and standard fertility care.
• Proceed with natural conception attempts or standard assisted reproductive technologies following the preconception phase.
• Participants will be followed to assess pregnancy outcomes and changes in biological aging hallmarks.

Conditions

Idiopathic Infertility; Infertility Unexplained; Infertility (IVF Patients); Infertility Female; Infertility Assisted Reproductive Technology

Keywords

Telomere dysfunction; Telomere attrition; Telomere biology; Cellular aging; Mitochondrial dysfunction; Cellular senescence; Reproductive aging; Functional infertility; Idiopathic infertility; Post-treatment unexplained infertility; Oocyte quality; Endometrial receptivity; Biomarkers of reproductive quality; Single-cell FISH; Leukocyte telomere length; Molecular etiology of infertility; Aging hallmarks; Traditional Chinese Medicine; Integrative fertility therapy; Nutraceutical support; Mitochondrial biogenesis; Oxidative stress; Reproductive resilience; Beyond Genomix

Outcome Measures

Primary Outcomes (1)

• Clinical Pregnancy Rate per Conception Attempt

  Clinical pregnancy defined as the presence of an intrauterine gestational sac confirmed by transvaginal ultrasound following a natural conception attempt or assisted reproductive technology (IUI or IVF) cycle.

  From initiation of the conception attempt until confirmation of clinical pregnancy, assessed up to 12 months.

Secondary Outcomes (7)

• Change in Percentage of Critically Short Telomeres (<5 kb)

  Assessed from baseline to 3 months after initiation of the integrative intervention; participants without sufficient biological response at 3 months may undergo a second assessment at 6 months.

• Change in Telomere Length Distribution Profile

  Assessed from baseline to 3 months after initiation of the integrative intervention; participants without sufficient biological response at 3 months may undergo a second assessment at 6 months.

• Change in Mean Leukocyte Telomere Length

  From baseline to 3 months after initiation of the integrative intervention, with an additional assessment at 6 months if the biological response at 3 months is insufficient.

• Change in Serum Anti-Müllerian Hormone (AMH) Level

  From baseline to 3 months after initiation of the integrative intervention, with an additional assessment at 6 months if the biological response at 3 months is insufficient.

• Change in Serum Follicle-Stimulating Hormone (FSH) Level

  From baseline to 3 months after initiation of the integrative intervention, with an additional assessment at 6 months if the biological response at 3 months is insufficient.

Study Arms (1)

Biological Aging-Informed Integrative Fertility Intervention

EXPERIMENTAL

Participants assigned to this arm undergo a baseline reproductive evaluation and molecular profiling related to biological aging, including leukocyte telomere analysis. Women presenting biological aging-related molecular signatures complete a personalized preconception integrative intervention lasting 4 to 12 weeks prior to natural conception attempts or IUI / IVF. The intervention combines individualized botanical formulations derived from TCM and targeted nutraceutical supplementation, administered alongside standard fertility care. These interventions are intended to support telomere-related cellular integrity, mitochondrial function, regulation of cellular senescence associated pathways, oxidative balance, and overall tissue homeostasis. Following the preconception phase, participants proceed with natural conception attempts or ART while continuing the integrative support. Clinical pregnancy outcomes \& changes in molecular and reproductive parameters are prospectively assessed.

Other: 1. Aging Hallmarks Biomarker Profiling (Telomere-Based); Other: 2. Integrative Botanical and Nutraceutical Intervention; Procedure: 3. Natural Conception or Assisted Reproductive Technologies

Interventions

1. Aging Hallmarks Biomarker Profiling (Telomere-Based) OTHER

Participants undergo baseline molecular profiling of biological aging biomarkers derived from the hallmarks of aging framework, with a primary focus on telomere-related parameters measured in peripheral blood leukocytes. Telomere analysis includes assessment of mean telomere length, the percentage of critically short ("super-short") telomeres, and telomere-length distribution profiles. Together, these biomarkers provide a measure of biological age and define molecular signatures of cellular aging relevant to ovarian and reproductive tissue function, including processes associated with telomere attrition, cellular senescence, and downstream aging hallmarks. Molecular parameters are assessed at baseline and, where applicable, longitudinally according to the study protocol for stratification and monitoring purposes.

Biological Aging-Informed Integrative Fertility Intervention

2. Integrative Botanical and Nutraceutical Intervention OTHER

Participants receive a personalized integrative intervention consisting of botanical formulations derived from Traditional Chinese Medicine (TCM) and targeted nutraceutical supplementation during a preconception period of 4 to 12 weeks. The intervention is administered alongside standard fertility care and is informed by biological aging-related molecular signatures. The integrative support is intended to address biological processes associated with aging hallmarks, including telomere-related cellular integrity, mitochondrial function, cellular senescence-associated pathways, oxidative balance, and tissue homeostasis.

Biological Aging-Informed Integrative Fertility Intervention

3. Natural Conception or Assisted Reproductive Technologies PROCEDURE

Following completion of the preconception phase and confirmation of stabilization of biological aging-related molecular profiles associated with the hallmarks of aging, participants proceed to conception attempts either through natural cycles or through assisted reproductive technologies, including intrauterine insemination (IUI) or in vitro fertilization (IVF), according to clinical indication. Assisted reproductive procedures are conducted in accordance with standard clinical practice and local guidelines. The choice of conception method is determined by routine clinical criteria and participant preference. No experimental modifications to standard ART protocols are introduced as part of this intervention.

Biological Aging-Informed Integrative Fertility Intervention

Eligibility Criteria

• Age: 25 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Biological female participants aged 25 to 42 years.
• Diagnosis of infertility defined as failure to conceive after at least 12 months of unprotected intercourse and/or repeated failure of assisted reproductive technologies (ART), including intrauterine insemination (IUI) and/or in vitro fertilization (IVF).
• History of post-treatment unexplained or functionally idiopathic infertility, defined as persistent infertility despite adequate correction or management of identifiable reproductive conditions (e.g., endometriosis, polycystic ovary syndrome, hormonal imbalance, uterine factors).
• Eligibility for natural conception attempts and/or assisted reproductive technologies according to routine clinical practice.
• Willingness to undergo biological aging biomarker profiling, including leukocyte telomere analysis.
• Ability and willingness to comply with study procedures, including the preconception integrative intervention and follow-up assessments.
• Provision of written informed consent prior to participation.

You may not qualify if:

• Current pregnancy or breastfeeding at the time of enrollment.
• Known chromosomal abnormalities or genetic conditions directly impairing fertility (e.g., Turner syndrome).
• Untreated severe male factor infertility precluding conception by natural or standard ART methods.
• Active malignancy or history of cancer requiring systemic treatment within the past 5 years.
• Severe systemic disease or medical condition contraindicating pregnancy or participation in ART (as determined by the treating physician).
• Use of investigational drugs or participation in another interventional clinical trial that could interfere with the study outcomes.
• Known hypersensitivity or contraindication to components of the integrative intervention, as determined by clinical assessment.
• Any condition which, in the opinion of the investigator, would interfere with safe participation or interpretation of study results.

Sponsors & Collaborators

• BEYOND GENOMiX SA, AG, Ltd: lead
• Praxis für Akupunktur und Chinesische Arzneimittel: collaborator
• Fertisuisse Ltd, SA, AG: collaborator

Study Sites (1)

BEYOND GENOMiX Research and Coordination Center

Neuchâtel, 2000, Switzerland

RECRUITING

Related Publications (6)

• Czamanski-Cohen J, Sarid O, Cwikel J, Douvdevani A, Levitas E, Lunenfeld E, Har-Vardi I. Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment. J Assist Reprod Genet. 2015 Nov;32(11):1697-703. doi: 10.1007/s10815-015-0581-4. Epub 2015 Oct 5.

  PMID: 26438644 BACKGROUND

• Ozturk S. The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection. Mech Ageing Dev. 2024 Apr;218:111913. doi: 10.1016/j.mad.2024.111913. Epub 2024 Feb 1.

  PMID: 38307343 BACKGROUND

• Zhou X, Smith DL, Lin J, HogenEsch E, Cedars MI. Telomere Length, Psychological Stress, and Infertility in Women of Advanced Reproductive Age. Endocrinology. 2025 Nov 6;166(12):bqaf163. doi: 10.1210/endocr/bqaf163.

  PMID: 41233938 BACKGROUND

• Ruth KS, Day FR, Hussain J, Martinez-Marchal A, Aiken CE, Azad A, Thompson DJ, Knoblochova L, Abe H, Tarry-Adkins JL, Gonzalez JM, Fontanillas P, Claringbould A, Bakker OB, Sulem P, Walters RG, Terao C, Turon S, Horikoshi M, Lin K, Onland-Moret NC, Sankar A, Hertz EPT, Timshel PN, Shukla V, Borup R, Olsen KW, Aguilera P, Ferrer-Roda M, Huang Y, Stankovic S, Timmers PRHJ, Ahearn TU, Alizadeh BZ, Naderi E, Andrulis IL, Arnold AM, Aronson KJ, Augustinsson A, Bandinelli S, Barbieri CM, Beaumont RN, Becher H, Beckmann MW, Benonisdottir S, Bergmann S, Bochud M, Boerwinkle E, Bojesen SE, Bolla MK, Boomsma DI, Bowker N, Brody JA, Broer L, Buring JE, Campbell A, Campbell H, Castelao JE, Catamo E, Chanock SJ, Chenevix-Trench G, Ciullo M, Corre T, Couch FJ, Cox A, Crisponi L, Cross SS, Cucca F, Czene K, Smith GD, de Geus EJCN, de Mutsert R, De Vivo I, Demerath EW, Dennis J, Dunning AM, Dwek M, Eriksson M, Esko T, Fasching PA, Faul JD, Ferrucci L, Franceschini N, Frayling TM, Gago-Dominguez M, Mezzavilla M, Garcia-Closas M, Gieger C, Giles GG, Grallert H, Gudbjartsson DF, Gudnason V, Guenel P, Haiman CA, Hakansson N, Hall P, Hayward C, He C, He W, Heiss G, Hoffding MK, Hopper JL, Hottenga JJ, Hu F, Hunter D, Ikram MA, Jackson RD, Joaquim MDR, John EM, Joshi PK, Karasik D, Kardia SLR, Kartsonaki C, Karlsson R, Kitahara CM, Kolcic I, Kooperberg C, Kraft P, Kurian AW, Kutalik Z, La Bianca M, LaChance G, Langenberg C, Launer LJ, Laven JSE, Lawlor DA, Le Marchand L, Li J, Lindblom A, Lindstrom S, Lindstrom T, Linet M, Liu Y, Liu S, Luan J, Magi R, Magnusson PKE, Mangino M, Mannermaa A, Marco B, Marten J, Martin NG, Mbarek H, McKnight B, Medland SE, Meisinger C, Meitinger T, Menni C, Metspalu A, Milani L, Milne RL, Montgomery GW, Mook-Kanamori DO, Mulas A, Mulligan AM, Murray A, Nalls MA, Newman A, Noordam R, Nutile T, Nyholt DR, Olshan AF, Olsson H, Painter JN, Patel AV, Pedersen NL, Perjakova N, Peters A, Peters U, Pharoah PDP, Polasek O, Porcu E, Psaty BM, Rahman I, Rennert G, Rennert HS, Ridker PM, Ring SM, Robino A, Rose LM, Rosendaal FR, Rossouw J, Rudan I, Rueedi R, Ruggiero D, Sala CF, Saloustros E, Sandler DP, Sanna S, Sawyer EJ, Sarnowski C, Schlessinger D, Schmidt MK, Schoemaker MJ, Schraut KE, Scott C, Shekari S, Shrikhande A, Smith AV, Smith BH, Smith JA, Sorice R, Southey MC, Spector TD, Spinelli JJ, Stampfer M, Stockl D, van Meurs JBJ, Strauch K, Styrkarsdottir U, Swerdlow AJ, Tanaka T, Teras LR, Teumer A, Thornorsteinsdottir U, Timpson NJ, Toniolo D, Traglia M, Troester MA, Truong T, Tyrrell J, Uitterlinden AG, Ulivi S, Vachon CM, Vitart V, Volker U, Vollenweider P, Volzke H, Wang Q, Wareham NJ, Weinberg CR, Weir DR, Wilcox AN, van Dijk KW, Willemsen G, Wilson JF, Wolffenbuttel BHR, Wolk A, Wood AR, Zhao W, Zygmunt M; Biobank-based Integrative Omics Study (BIOS) Consortium; eQTLGen Consortium; Biobank Japan Project; China Kadoorie Biobank Collaborative Group; kConFab Investigators; LifeLines Cohort Study; InterAct consortium; 23andMe Research Team; Chen Z, Li L, Franke L, Burgess S, Deelen P, Pers TH, Grondahl ML, Andersen CY, Pujol A, Lopez-Contreras AJ, Daniel JA, Stefansson K, Chang-Claude J, van der Schouw YT, Lunetta KL, Chasman DI, Easton DF, Visser JA, Ozanne SE, Namekawa SH, Solc P, Murabito JM, Ong KK, Hoffmann ER, Murray A, Roig I, Perry JRB. Genetic insights into biological mechanisms governing human ovarian ageing. Nature. 2021 Aug;596(7872):393-397. doi: 10.1038/s41586-021-03779-7. Epub 2021 Aug 4.

  PMID: 34349265 BACKGROUND

• M'kacher R, Colicchio B, Marquet V, Borie C, Najar W, Hempel WM, Heidingsfelder L, Oudrhiri N, Al Jawhari M, Wilhelm-Murer N, Miguet M, Dieterlen A, Deschenes G, Tabet AC, Junker S, Grynberg M, Fenech M, Bennaceur-Griscelli A, Voisin P, Carde P, Jeandidier E, Yardin C. Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility. Fertil Steril. 2021 Jan;115(1):164-173. doi: 10.1016/j.fertnstert.2020.07.005. Epub 2020 Dec 4.

  PMID: 33272625 BACKGROUND

• Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039.

  PMID: 23746838 BACKGROUND

MeSH Terms

Conditions

Infertility; Infertility, Female; Mitochondrial Diseases

Interventions

Reproductive Techniques, Assisted

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Reproductive Techniques; Therapeutics; Investigative Techniques

Central Study Contacts

M. MERARCHI

CONTACT

+4132 552 60 00; pm@beyondgenomix.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study. No parties are masked to the intervention. Participants, investigators, and assessors are aware of the assigned treatment.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open-label interventional study evaluating a personalized telomere-guided therapeutic approach in women with post-treatment unexplained (functionally idiopathic) infertility. Each participant receives an individualized integrative protocol tailored to her telomere molecular profile and interconnected aging hallmarks, including mitochondrial dysfunction and cellular senescence. The intervention combines TCM formulations with targeted nutraceutical support to restore telomere integrity, enhance mitochondrial activity, and reduce senescence, as reflected by the percentage of super-short telomeres (\<5 kb). The study includes three phases: baseline telomere and reproductive assessment, a 4-12 week preconception phase with personalized therapy, and a conception phase (natural or ART) under continued integrative care. The primary outcome is the restoration of reproductive quality through telomere and related pathways rejuvenation, to improve oocyte competence.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: February 12, 2026
• Study Start: January 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

CH (1)