Background <p>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.</p> Methods <p>In this prospective, observational pilot feasibility study, eight healthy women aged 18–35 years with regular menstrual cycles and BMI &lt; 30 underwent serial intrauterine pO₂ measurements across the luteal phase during a single natural cycle. Measurements were scheduled approximately every 48&#xa0;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&#xa0;mm fiber optic microsensor positioned 1&#xa0;cm from the uterine fundus under ultrasound guidance. The primary outcome was intrauterine pO₂ (Torr) across the luteal phase.</p> Results <p>Two distinct intrauterine oxygenation profiles were identified. Four participants exhibited a “peak” pattern characterized by early luteal low pO₂ (&lt; 15&#xa0;Torr), followed by a sharp mid-luteal rise in pO₂ (40–45&#xa0;Torr at LH + 4 to LH + 6, <i>p</i> &lt; 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 &lt; 35&#xa0;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.</p> Conclusions <p>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.</p> Trial registration <p>ISRCTN85528745 (retrospectively registered on 30/01/2026).</p>

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

  • Anna Teixidó Troyano,
  • Melchor Carbonell Socias,
  • Carmen Cabeza Oliver,
  • Elisabeth Sanfeliu de España,
  • Vicenç Font Zabalia,
  • Lidia Illan Hernandez,
  • Maria Antonia Perelló Barceló,
  • Maria Luisa Pancorbo Lerma,
  • Elisabet Robert Marchal,
  • Manel Mendoza Cobaleda,
  • Roger Gallart Agut,
  • Luis Manuel Artiles Martínez,
  • Monica Rodríguez de la Vega Otazo,
  • Anna Suy Franch,
  • Julio Herrero García

摘要

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).