Real-time intrauterine dissolved oxygen dynamics across the luteal phase: a potential non-invasive functional biomarker of endometrial status

BACKGROUND: Accurate, same-cycle assessment of endometrial readiness remains a major unmet need in assisted reproduction. Animal models have shown that spiral artery angiogenesis drives a midluteal rise in uterine oxygen tension, but direct, real-time measurements in humans have never been reported. We hypothesized that intrauterine dissolved O₂ profiling during the luteal phase could represent a potential functional, noninvasive biomarker of endometrial status. METHODS: In this prospective, observational pilot feasibility study, eight healthy women aged 18-35 years with regular menstrual cycles and BMI < 30 underwent serial intrauterine pO₂ measurements across the luteal phase during a single natural cycle. Measurements were scheduled approximately every 48 h from the day of the LH surge (LH + 0) up to LH + 13/14, with minor variations due to scheduling constraints. Dissolved oxygen was recorded using a 1 mm fiber optic microsensor positioned 1 cm from the uterine fundus under ultrasound guidance. The primary outcome was intrauterine pO₂ (Torr) across the luteal phase. RESULTS: Two distinct intrauterine oxygenation profiles were identified. Four participants exhibited a "peak" pattern characterized by early luteal low pO₂ (< 15 Torr), followed by a sharp mid-luteal rise in pO₂ (40-45 Torr at LH + 4 to LH + 6, p < 0.0001), a short plateau, and a decline by LH + 8. One participant showed an earlier and abbreviated peak. The remaining four participants maintained pO₂ values < 35 Torr throughout the luteal phase ("no-peak" pattern). Post-hoc review of baseline screening data and follow-up participant interviews identified plausible physiological, pharmacological, or lifestyle-related factors that may influence endometrial vascular maturation in the no-peak subgroup. CONCLUSIONS: This study provides the first in vivo characterization of real-time intrauterine oxygen dynamics across the luteal phase in women. Intrauterine pO₂ profiling identified distinct temporal oxygenation patterns across the luteal phase and may reflect physiologically relevant changes in endometrial function. These preliminary findings support further evaluation of intrauterine oxygen profiling as a potential non-invasive, same-cycle functional biomarker of embryo-endometrium synchrony. Larger studies are required to validate its predictive value for implantation and live birth outcomes. TRIAL REGISTRATION: ISRCTN85528745 (retrospectively registered on 30/01/2026).