ArticleOxidative stress in follicular fluid of young women with low response compared with fertile oocyte donors
Introduction
IVF is one of the most common assisted reproduction techniques. This method is a widely accepted infertility treatment and often remains the only chance for infertile couples of having a baby. Unfortunately, the success of this technique, measured as an average pregnancy rate per cycle, is only 30–40% (Das et al, 2006, Gerris et al, 1999). Remarkably, reduced ovarian reserve (follicle number remaining in the ovarian pool), irrespective of age, is also associated with a decrease in pregnancy rate (Moolenaar et al., 2013).
Among the many reasons for the IVF failure, oxidative stress seems to be an important factor (Sikka, 2004). In the female reproductive system, oxidative stress and antioxidants perform physiological roles during folliculogenesis and oocyte maturation and may also be related to conditions that limit the success of assisted reproductive techniques (Pacella et al., 2012). Although there is also some evidence for the role of reactive oxygen species (ROS) in the pathophysiology of infertility and assisted fertility (Agarwal, Allamaneni, 2004, Gupta et al, 2009), the existing data are conflicting and the effect of oxidative stress on the outcome of IVF is not clear (Fujimoto et al, 2011, Jozwik et al, 1999).
Several studies have focused on the micro-environment surrounding the oocyte and on ROS and antioxidants found in the follicular fluid (Agarwal et al, 2012, Revelli et al, 2009). Follicular fluid creates the micro-environment for the developing oocyte and has a direct impact on oocyte quality, implantation and early embryo development. An imbalance in ROS production in ovarian follicular fluid may have an adverse effect on the above processes. Otherwise, oocyte growth and maturation appear to be affected by nutritional imbalances, hormonal disturbances and physical conditions of the micro-environment, such as oxidative stress (Borowiecka et al., 2012).
Sufficient antioxidant capacity of follicular fluid during oocyte retrieval has also been associated with characteristics of IVF success (Aydin et al, 2013a, Aydin et al, 2013b, Younis et al, 2012); however, studies analysing the relationship between the level of oxidative stress in the follicular fluid and reduced ovarian reserve/response in women undergoing gonadotrophin stimulation are lacking. Blood collected from women undergoing ovarian stimulation for IVF or intrauterine insemination (IUI) allow a unique opportunity to investigate associations between different oxidative stress metabolites and various events in the reproductive process (Younis et al., 2014). Thus far, little is known about how alteration of the follicular environment as a result of oxidative stress leads to a reduced ovarian reserve.
The objective of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with fertile oocyte donors and high responder patients of the same age, to assess the oxidative stress impact on ovarian reserve (Núñez-Calonge et al., 2014).
To our knowledge, no study in the literature has examined the correlation between follicular fluid total oxidant and antioxidant concentrations and low response to gonadotrophin stimulation in young women undergoing assisted reproductive treatment.
Section snippets
Study participants and ovarian stimulation protocols
This prospective clinical study was conducted at Clinica Tambre during the period of November 2013 to June 2015, was approved by the Ethical Review Board of the Hospital de la Princesa (Madrid, Spain) on 27 September 2012 (reference PI-648), and included 30 healthy fertile oocyte donors, eight women with high response (>10 oocytes retrieved) to ovarian stimulation and 22 women with low response (<5 oocytes retrieved) in at least one previous ovarian stimulation cycle.
Patients were recruited
Results
The clinical characteristics of the study population are represented in Table 1, by age group and response levels in terms of BMI, anti-Müllerian hormone (AMH), amount of basal FSH, amount of administered FSH, the oestradiol value on the day of HCG/GnRH injection and number of oocytes retrieved.
No statistical difference was found in the amount of total gonadotrophin used for ovarian stimulation for poor responders, compared with non-poor responders groups. Serum oestradiol concentrations on the
Discussion
The biochemical composition of follicular fluid includes proteins, sugars, ROS, antioxidants and hormones (O'Gorman et al., 2013). These mediators may have a direct effect on the maturation ability and the quality of oocytes (Agarwal et al., 2012). Moreover, the oxidant–antioxidant state of follicular fluid and its effects on oocyte and IVF outcomes has been of great interest in recent years (Oyawoye et al, 2003, Revelli et al, 2009).
The aim of this study was to investigate the relationship
Acknowledgements
Fundacion Tambre (Grant no. FT-112) supported this work. We thank our colleagues from the Tambre Clinic for their assistance in sample collection, and all donors and patients for their participation in the study.
Dr Rocío Nuñez-Calonge is senior embryologist and scientific director of Clinica Tambre, and associate professor of Master in Reproductive Medicine at Complutense University in Madrid, where she received her PhD in 1991. She has worked in the area of reproductive technologies since 1985 and performed a post-doctoral fellowship at the Centre for Research on Reproduction and Women's Health, Philadelphia, USA. Dr Nunez-Calonge has published numerous articles and chapters in scientific journals and
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Dr Rocío Nuñez-Calonge is senior embryologist and scientific director of Clinica Tambre, and associate professor of Master in Reproductive Medicine at Complutense University in Madrid, where she received her PhD in 1991. She has worked in the area of reproductive technologies since 1985 and performed a post-doctoral fellowship at the Centre for Research on Reproduction and Women's Health, Philadelphia, USA. Dr Nunez-Calonge has published numerous articles and chapters in scientific journals and books and is referee for a number of Spanish scientific journals. Her primary areas of research are embryology and male infertility.