A Korean study of follicular fluid from 106 patients found a weak association between a DNA fragmentation measure and embryo morphology. Whether it can predict pregnancy or birth remains an open question.
A good-looking embryo is an encouraging first step in IVF, but appearance cannot guarantee pregnancy. An embryo with a lower morphological grade can also result in a healthy baby. Could the environment in which an egg grew provide information its appearance does not reveal?
Researchers from CHA University and the CHA fertility center studied fragments of cell-free DNA in the fluid surrounding the egg. Their findings appeared November 2 in Frontiers in Endocrinology.
What follicular fluid can tell researchers
An ovarian follicle is a small sac in which an egg grows. Its fluid contains hormones, proteins and metabolites that help provide an environment for growth and maturation. Follicular fluid can be collected along with the egg at retrieval, giving researchers a window into that environment.
Cell-free DNA consists of fragments released outside cells, including during cell damage or death. The investigators examined both the amount of DNA and how fragmented it was. This DNA does not come directly from the embryo. It chiefly reflects activity and damage in the cells of the follicle, providing an indirect measure of the egg's surroundings.
Comparing 106 samples with blastocyst grades
Researchers at one Korean fertility center evaluated women aged 29–47 who underwent IVF with intracytoplasmic sperm injection (ICSI). They compared follicular fluid DNA characteristics with the morphology of the resulting blastocysts.
The ALU247/115 ratio compares DNA sequences of two lengths as an indicator of molecular integrity. A lower ratio generally indicates greater fragmentation. Across 106 women, the ratio had a statistically significant but weak correlation with the embryo morphology score (r = 0.23). Lower scores denoted better morphology in this grading system. A higher ratio therefore tended to accompany a poorer grade.
The investigators also compared three embryo groups. The mean ratio was 1.05 in fluid corresponding to 42 good-quality embryos and 1.24 for 10 low-grade embryos. The structural measure may carry information about morphology, but the relationship was too weak to classify an individual embryo reliably on that basis.
Age groups and the limits of the comparison
The correlation was 0.38 in 31 women younger than 35 and 0.32 in 40 women aged 35–39. Both associations were statistically significant. Among 35 women aged 40 or older, the correlation was 0.21 and did not reach statistical significance.
The pattern raises a question about age, but it does not show that the marker is uninformative after 40. The analysis included only embryos that reached the blastocyst stage. Embryos that stopped developing earlier were excluded, a design feature the authors noted could affect the findings in older women.
Looking beyond an embryo's appearance
IVF laboratories routinely assess developmental progress, cell arrangement and shape. Morphology alone cannot establish chromosome status, implantation potential or whether a transfer will result in a birth. Researchers are therefore examining molecular information in culture media and follicular fluid alongside visual assessment.
This study looked upstream of fertilization, at the environment of the growing egg. The ratio reflecting DNA integrity showed a clearer association with morphology than the absolute amount of DNA. Whether this adds practical information to existing assessment methods is unknown.
Can follicular fluid predict pregnancy?
The study measured morphology. It did not use preimplantation genetic testing for aneuploidy (PGT-A) to assess embryo chromosomes or evaluate implantation, clinical pregnancy or live birth. It could not determine whether a fluid sample can identify the embryo most likely to result in a baby.
The small, single-center pilot provides a reason to study molecular traces in the follicle. Larger investigations will need to compare them with chromosome status and outcomes through birth before the measure could be used clinically.
Source: “Cell-free DNA in human ovarian follicular fluid as a potential biomarker of embryo quality in IVF cycles: a pilot study.” CHA University School of Medicine and CHA fertility center investigators. Frontiers in Endocrinology, November 2026, volume 17, article 1959981. DOI: 10.3389/fendo.2026.1959981.
Related reading: Why AMH alone cannot predict egg yield: 2,162 IVF cycles.
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