Cell-free DNA in human ovarian follicular fluid as a potential biomarker of embryo quality in IVF cycles: a pilot study
4 affiliations
- 1CHA Fertility Center Seoul Station, CHA University School of Medicine
- 2CHA Fertility Center Gangnam, Fertility Laboratory
- 3CHA Fertility Center Gangnam, CHA University School of Medicine
- 4CHA Fertility Center Bundang, CHA University School of Medicine
Abstract
Introduction: There is growing interest in evaluating cell-free DNA (cfDNA) in follicular fluid (FF) as a molecular feature of the follicular microenvironment and examining its association with subsequent embryo development. This exploratory pilot study aimed to investigate the association between FF cfDNA integrity, measured by the Arthrobacter luteus (ALU) 247/115 ratio, and morphology-based embryo quality in IVF cycles.
Methods: This observational study analyzed 106 follicular fluid samples from patients undergoing IVF with intracytoplasmic sperm injection (ICSI) at a single fertility center. FF samples were collected during ovum pick-up, and cfDNA concentrations were quantified using ALU-quantitative PCR. To evaluate the ALU247/115 ratio in relation to age, participants were categorized into three age groups.
Results: The ALU247/115 ratio showed a significant but weak positive correlation with embryo quality score across all patients (n = 106, r = 0.23, p = 0.016). Subgroup analysis revealed stronger correlations in women under 35 years (n = 31, r = 0.38, p = 0.035) and those aged 35–39 years (n =40, r = 0.32, p = 0.044). No significant correlation was observed in women aged 40 or older (n = 35, r = 0.21, p = 0.225).
Conclusions: In women under 40, increased cfDNA fragmentation in FF was associated with lower morphology-based embryo quality. However, the observed correlations were modest, and the absence of preimplantation genetic testing for aneuploidy (PGT-A), implantation, clinical pregnancy, and live birth outcomes limits clinical interpretation. These exploratory findings do not establish FF cfDNA as a clinically validated predictive biomarker or demonstrate that it improves embryo selection. Larger prospective studies incorporating embryo ploidy and clinically relevant reproductive outcomes are warranted.
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BibTeX
@article{jo2026cellfree,
title = {{Cell-free DNA in human ovarian follicular fluid as a potential biomarker of embryo quality in IVF cycles: a pilot study}},
author = {Eun-Hye Jo and Tae Hyung Kim and Jin Hee EUM and Jihye Jeong and Sol A YOON and Min Kyoung Kim and Jee Hyun Kim and Hee Jun Lee},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1959981},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1959981/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cell-free DNA in human ovarian follicular fluid as a potential biomarker of embryo quality in IVF cycles: a pilot study
AU - Eun-Hye Jo
AU - Tae Hyung Kim
AU - Jin Hee EUM
AU - Jihye Jeong
AU - Sol A YOON
AU - Min Kyoung Kim
AU - Jee Hyun Kim
AU - Hee Jun Lee
PY - 2026
DA - 2026/11/02
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1959981
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1959981/full
AB - Introduction: There is growing interest in evaluating cell-free DNA (cfDNA) in follicular fluid (FF) as a molecular feature of the follicular microenvironment and examining its association with subsequent embryo development. This exploratory pilot study aimed to investigate the association between FF cfDNA integrity, measured by the Arthrobacter luteus (ALU) 247/115 ratio, and morphology-based embryo quality in IVF cycles. Methods: This observational study analyzed 106 follicular fluid samples from patients undergoing IVF with intracytoplasmic sperm injection (ICSI) at a single fertility center. FF samples were collected during ovum pick-up, and cfDNA concentrations were quantified using ALU-quantitative PCR. To evaluate the ALU247/115 ratio in relation to age, participants were categorized into three age groups. Results: The ALU247/115 ratio showed a significant but weak positive correlation with embryo quality score across all patients (n = 106, r = 0.23, p = 0.016). Subgroup analysis revealed stronger correlations in women under 35 years (n = 31, r = 0.38, p = 0.035) and those aged 35–39 years (n =40, r = 0.32, p = 0.044). No significant correlation was observed in women aged 40 or older (n = 35, r = 0.21, p = 0.225). Conclusions: In women under 40, increased cfDNA fragmentation in FF was associated with lower morphology-based embryo quality. However, the observed correlations were modest, and the absence of preimplantation genetic testing for aneuploidy (PGT-A), implantation, clinical pregnancy, and live birth outcomes limits clinical interpretation. These exploratory findings do not establish FF cfDNA as a clinically validated predictive biomarker or demonstrate that it improves embryo selection. Larger prospective studies incorporating embryo ploidy and clinically relevant reproductive outcomes are warranted.
SN - 1664-2392
ER -