Oyawoye, OA; (2006) The role of ovarian follicular antioxidants and reactive oxygen species in human female reproduction. Doctoral thesis , UCL (University College London).

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Abstract

Infertility affects about 15% of couples and in many cases the aetiology is easily identified. Aetiological diagnosis is more difficult in about 15% of females, when infertility is related to less clearly identifiable factors such as luteal phase deficiency and endometriosis. It has been suggested that oxidative stress may interfere with female fertility, analogous to the situation in males, and may play a role in some cases of unexplained fertility. This study was designed to evaluate the role of follicular fluid oxidative stress in female reproduction. Follicular fluid total antioxidant capacity (TAC) and TAC loss, indirect measures of oxidative stress, were related to early reproductive outcome, specifically oocyte recovery, fertilisation, and subsequent embryo viability after 3 days in culture. Follicular TAC was assayed in a pilot study using two methods - the trolox equivalent antioxidant capacity (TEAC) assay and the ferric reducing/antioxidant power (FRAP) assay - to determine the optimum assay for TAC. Good correlation was observed between the assays. The FRAP assay methodology was robust, easier, cheaper and quicker to perform, and was therefore used to determine follicular fluid TAC in the rest of the study. Follicular fluid TAC was unrelated to the presence of an oocyte in the source follicle. Oocytes from follicles with lower TAC tended to fail to fertilise, whereas oocytes from follicles that exhibited mid-range and higher TAC were fertilisation competent. Furthermore, high follicular TAC at oocyte retrieval was associated with embryo non-viability, whereas mid-range follicular TAC values were associated with embryo viability after 3 days. Outside of the IVF setting, in women undergoing natural menstrual cycles (i.e. no exposure to hormonal preparations), follicular TAC was similar in sub-fertile women and in fertile controls. Follicular fluid proteins were estimated by Bradford assay because of the contribution of their sulphydryl group to antioxidant activity. Follicular fluid sulphydryl content was also correlated with TAC. The total follicular protein concentration was relatively consistent (37.5 6.1 mg/ml). Sulphydryl content of follicular fluid corresponded to about 40% of TAC values. No correlation existed between protein and TAC, indicating that variations in TAC values were not just due to changes in protein. Follicular total protein concentration had no influence on reproductive outcome. Follicular fluid cell density varied widely between patients and between different follicles from the same patient. There was no correlation between follicular fluid cell density and TAC. These results suggest that the role of oxygen free radicals and antioxidants in female reproduction are complex. A lesser ability to defend against free radicals within the follicle is detrimental to oocyte fertilisation, at least in the IVF setting. It is possible such oocytes suffer free radical damage during their development, which compromises fertilisation competence. Excessive TAC however impairs subsequent embryo viability, suggesting that free radicals are also required for some oocyte maturation processes which influence subsequent developmental competence, which if excessively quenched impair viability. The use of exogenous antioxidants to improve fertility in women cannot yet be justified.

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