[eng] Background: In vitro fertilization (IVF) outcomes are influenced by various factors,
including the quality of the oocyte which may be impacted by genetic and environmental
conditions. Recent advancements in reproductive medicine have highlighted follicular
fluid analysis as a non-invasive method to identify biomarkers predictive of embryo
implantation potential and overall IVF success. Among these, cell-free mitochondrial
DNA (cf-mtDNA) has emerged as a promising candidate, with its mutations potentially
indicating oocyte quality and embryo viability.
Objective: Our aim is to explore the impact of IVF ovarian stimulation treatment on the
accumulation of mitochondrial DNA (mtDNA) mutations in follicular fluid and assess
their implications on IVF outcomes.
Methods: This study enrolled 24 women under 35 years old undergoing their first IVF
cycle without known infertility issues. For each woman, we collected a blood sample
prior to ovarian stimulation and a follicular fluid sample at the time of oocyte retrieval.
Long-PCR amplification and next-generation sequencing were used to identify mtDNA
mutations. Embryo quality was assessed using the ASEBIR scoring system.
Results: The ovarian stimulation step was associated with the induction of mtDNA
mutations, reflected on the cf-mtDNA within follicular fluid, predominantly in the D-loop
region. These mutations correlated with a lower oocyte count and poorer embryo quality,
negatively impacting IVF outcomes. The accumulation of these mutations showed a timedependent pattern, with longer treatments leading to more mutations and lower pregnancy
rates, likely due to increased oxidative stress and its deleterious effects on oocyte quality.
Conclusions: The study establishes a link between mtDNA mutations in follicular fluid
and reduced IVF efficacy, suggesting that such mutations could serve as non-invasive
biomarkers for predicting IVF outcomes. This research paves the way for future
investigations in the field of IVF with the aim of improving protocols by shortening the
duration of ovarian stimulation or using antioxidants to reduce the mtDNA mutation rates.
Altogether, it will lead to improved IVF outcomes and ultimately benefiting our patients