The Molecular Landscape of Nitric Oxide in Ovarian Function and IVF Success: Bridging Redox Biology and Reproductive Outcomes

The Molecular Landscape of Nitric Oxide in Ovarian Function and IVF Success: Bridging Redox Biology and Reproductive Outcomes

<b>Background</b>: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO<sub>3</sub><sup>−</sup>) and nitrite (NO<sub>2</sub><sup&...

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Main Authors:	Diamandis Athanasiou, Charalampos Voros, Ntilay Soyhan, Georgia Panagou, Maria Sakellariou, Despoina Mavrogianni, Eleni Sivylla Bikouvaraki, George Daskalakis, Kalliopi Pappa
Format:	Article
Language:	English
Published:	MDPI AG 2025-07-01
Series:	Biomedicines
Subjects:	nitric oxide follicular fluid IVF oocyte quality embryo development oxidative stress
Online Access:	https://www.mdpi.com/2227-9059/13/7/1748
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Summary:	<b>Background</b>: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO<sub>3</sub><sup>−</sup>) and nitrite (NO<sub>2</sub><sup>−</sup>) may indicate real-time follicular function during IVF. <b>Methods</b>: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO<sub>2</sub>-NO<sub>3</sub> concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. <b>Results</b>: Higher NO<sub>2</sub>-NO<sub>3</sub> levels were substantially associated with increased total oocyte count, MII oocytes (<i>p</i> = 0.014), and 2PN embryos (<i>p</i> = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO<sub>2</sub>-NO<sub>3</sub> levels showed a positive correlation with estradiol (<i>p</i> < 0.001) and progesterone (<i>p</i> < 0.001), suggesting a possible function in granulosa cell steroidogenesis. <b>Conclusions</b>: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve.
ISSN:	2227-9059