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OXIDATIVE STRESS MARKERS IN FOLLICULAR FLUID OF YOUNG WOMEN WITH LOW RESPONSE IN OVARIAN STIMULATION DURING IN VITRO FERTILIZATION COMPARED TO FERTILE OOCYTE DONORS. . R. NUÑEZ-CALONGE 1 , S.CORTES 1 , P.CABALLERO 1 , E.VARA 2 , R. KIREEV 2 , J.FERNANDEZ-TRESGUERRES 2 .
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OXIDATIVE STRESS MARKERS IN FOLLICULAR FLUID OF YOUNG WOMEN WITH LOW RESPONSE IN OVARIAN STIMULATION DURING IN VITRO FERTILIZATION COMPARED TO FERTILE OOCYTE DONORS. R. NUÑEZ-CALONGE1, S.CORTES1, P.CABALLERO1, E.VARA2, R. KIREEV2, J.FERNANDEZ-TRESGUERRES2. 1 Clínica Tambre, Madrid 2 Dpto. Fisiología, Universidad Complutense Madrid
Introduction There are not enough studies analyzing the relationship between OS and reduced ovarian reserve in women undergoing gonadotropin stimulation.
Hypothesis One of the causes that could lead to low ovarian reserve in young women could be oxidative stress.
Objective To determine the levels of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid (FF) of young women with low response in controlled ovarian stimulation cycles compared with fertile oocytes donors, to assess the oxidative stress impact on ovarian reserve.
Methods 25 low responders Patients (< 35 years old) COS 30 healthy, fertile, Donors (< 35 years old) rFSH+ antagonist GnRH
Methods 2.900 rpm, 10´ • Antioxidant enzymes : Glutathione peroxidase (GPx) • Glutathione transferase (GST) • Oxidative stress markers: Malondialdehide (MDA) • Inflammatory markers: Interleukine 6 (IL-6) • Interleukine 8 (IL 8) • Tumoral necrosis factor alpha (TNF α) • Vascular Endotelial Growth Factor (VEFG)
Results Antioxidant enzymes p<0.05
Results Antioxidant enzymes NS
Results Oxidative stress marker p<0.01
Results Inflammatory markers p<0.001
Results Inflammatory markers NS
Results Inflammatory markers NS
Results Inflammatory markers NS
Summary • The antioxidant GST has been found to be decreased in patients with low response to COS. • MDA, as one of the most important markers of OS, as well as the proinflammatory cytoquine IL-6, have been found to be increase in patients with reduced ovarian reserve. • However, therelations of some antioxidant enzymes like GPx, and cytokines (IL-8, TNF-alfa and VEGF) with OS and its implication in ovarian reserve needs to be addressed.
Conclussions • This is the first study analysing the relationship between oxidative stress and low response in young patients undergoing controlled ovarian stimulation cycles compared with fertile oocytes donors. The results show that the most plausible explanation for low response in young women is an increase in oxidative stress. • Our results demonstrate that different levels of OS markers, oxidant enzymes and cytokines in low responder patients as compared to oocyte donors may have a negative impact on ovarian response.
Conclussions A better knowledge of these alterations could lead to the development of specific antioxidant therapies for women with poor prognosis undergoing IVF treatment.