Vasoactive endothelial factors in women with poor and suboptimal ovarian response during infertility treatment using assisted reproductive technologies

Objective: To investigate the levels of vasoactive endothelial factors, endothelin-1, and final metabolites of nitric oxide in the blood and follicular fluid, along with the expression levels of endothelial and inducible nitric oxide synthase (eNOS and iNOS) in cumulus cells of women with varying outcomes of hormonal ovarian stimulation during assisted reproductive technology (ART) for infertility treatment.

Materials and methods: In a simple open comparative clinical trial with parallel groups, markers of endothelial dysfunction were analyzed in 71 women from the Volgograd region, aged up to 42 years, undergoing ART for infertility treatment. The control group, with a normal and high response to ovarian stimulation using gonadotropins, included 31 women (≥10 oocytes retrieved). Two groups were formed with suboptimal (5–9 oocytes retrieved) and poor responses (4 or fewer oocytes retrieved), each containing 20 women. All patients had anti-Müllerian hormone levels greater than 1.2 ng/mL. Endothelin-1 levels in the blood and follicular fluid were determined using enzyme-linked immunosorbent assay, while the levels of eNOS and iNOS were assessed in cumulus cell lysates. The concentration of final nitric oxide metabolites (nitrite and nitrate ions) in the blood serum and follicular fluid was determined using the method described by Metelskaya V.A. and Gumanova N.G. (2005).

Results: Women with a poor response had significantly higher levels of endothelin-1 and end metabolites of nitric oxide in the blood serum than those with a high and normal response. The amount of iNOS in cumulus cell lysates from women with suboptimal and poor responses was greater than that in the control group. This, combined with the increased concentration of nitrite and nitrate ions, may indicate the formation of a potent oxidant, peroxynitrite, potentially causing irreversible damage in the cells of patients with a poor response.

Conclusion: Changes in vasoactive endothelial factor levels may contribute to a reduced response to ovarian stimulation with gonadotropins during ART for infertility treatment. Further research into the mechanisms that determine oocyte quality and quantity can enable personalized approaches to infertility treatment, potentially increasing pregnancy rates.