**Background:** The global increase in life expectancy and the social trend of postponing childbearing have intensified research on aging and female fertility. Chronological age alone does not fully capture an individual's physiological state; biological age, influenced by epigenetic modifications (particularly DNA methylation), may provide a more accurate reflection. Epigenetic clocks are mathematical models that predict biological age from DNA methylation patterns. This narrative review examines the evidence linking epigenetic clocks to female fertility, encompassing both infertility and pregnancy outcomes.
**Methods:** The authors conducted a narrative review of studies investigating epigenetic clocks in the context of female reproductive health. Studies were categorized by tissue type (endometrium, peripheral blood, ovarian cells, placenta, cord blood) and by reproductive phase (infertility and pregnancy). Key epigenetic clocks discussed include the Horvath clock (multi-tissue, first-generation), Hannum clock (blood-based), PhenoAge, GrimAge (second-generation, linked to morbidity/mortality), DunedinPoAm (pace of aging), and tissue-specific clocks (e.g., placental GA clock, granulosa cell clock).
**Key Results:**
- **Infertility:** In peripheral blood, Monseur et al. (2020) found that women with positive age acceleration had lower AMH (1.29 vs. 2.29 ng/mL, p=0.05), lower AFC (8 vs. 14.5, p=0.05), and fewer oocytes retrieved (5.5 vs. 14.5, p=0.002). Li Piani et al. (2022) reported that women who conceived after ART were epigenetically younger than those who did not (36.1 ± 4.2 vs. 37.3 ± 3.3 years, p<0.04), and this remained significant after adjusting for AFC, FSH, and oocyte number (p=0.028). Lee et al. (2022) found that ART mothers aged 0.021 years faster than non-ART mothers using the DunedinPoAm clock (p<0.03). In ovarian tissues, cumulus granulosa cells were consistently epigenetically younger than chronological age (e.g., 8.6 ± 2.1 vs. 35.3 ± 4.1 years in Hanson et al., 2020). Knight et al. (2022) showed GrimAge acceleration was negatively associated with AMH (p=0.003), AFC (p=0.0001), and mature oocyte count (p=0.0003).
- **Pregnancy:** Placental clocks (Mayne et al., 2017; Lee et al., 2019) accurately estimated gestational age. Early-onset preeclampsia was associated with accelerated placental aging (p<0.001). Cord blood clocks (Bohlin et al., 2016; Knight et al., 2016; Haftorn et al., 2021) predicted gestational age with high accuracy (EPIC clock R²=0.724, MAD=3.24 days). GA acceleration significantly predicted birthweight (p=0.033). Ross et al. (2020) found higher maternal GrimAge acceleration was associated with lower birthweight (p=0.001). Shiau et al. (2021) reported that children exposed to gestational diabetes had higher age acceleration (Horvath: +4.96 months, p=0.0002; Hannum: +11.2 months, p<0.0001). Nwanaji-Enwerem et al. (2021a) showed that maternal adverse childhood events were associated with 0.76-year greater Horvath clock age acceleration in children (p=0.004).
**Clinical Implications:** Epigenetic clocks may serve as biomarkers for ovarian aging, ART success prediction, and pregnancy risk stratification. The concept of infertility as an 'accelerated aging disease' could shift reproductive medicine toward preventive health. In pregnancy, epigenetic gestational age estimators could improve fetal maturity assessment, especially when LMP is uncertain. The evidence also suggests that maternal health and early-life exposures have lasting epigenetic effects on offspring, supporting the DOHaD framework. However, the authors emphasize that validated, standardized instruments are still missing, and most studies are limited by small sample sizes, heterogeneous clocks, and lack of fertile control groups. Future research should focus on developing tissue-specific clocks, validating them in diverse populations, and exploring whether lifestyle interventions can modulate epigenetic aging in the reproductive context.