The role of ovarian follicular biophysical and metabolic markers of oocyte viability in the pathophysiology of subfertility

• Main Author: Baskind, Nadine Ellissa
• Published: University of Leeds 2012
• Subjects: 612.625
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608362

Oocyte to ovarian somatic cell bi-directional communication is mediated by multiple cytokines/growth factors. During the course of folliculo- and oogenesis, cytokines participate in regulating oocyte's growth, vasculogenesis and steroid synthesis. This study aimed to combine follicular antral volume and peri-follicular vascularity (PBF) with analysis of the cytokine and metabolic contents of the follicular fluid (FF) and track the oocyte to its fate in order to ascertain whether these reflected oocyte maturity, fertilisation potential and embryo viability. The pre-ovulatory FF from individual follicles from patients undergoing natural cycle (Ne) IVF/IVF-ICSI (retrieved also at various time points during the follicular phase prior to the treatment cycle) or following controlled ovarian hyperstimulation (COH) was retrieved in four cohorts of patients including ovulatory women with a normal pelvis and women with subfertility-related pathology. The PBF was graded prior to follicular aspiration and the antral volume recorded. Multiple FF cytokine levels were determined by multiplex fluid-phase immunoassay and metabolite profiling was performed using NMR spectroscopy. The NC study showed that biophysical, cytokine and metabolic profiles all altered during the follicular phase; PBF increased whilst pro-angiogenic and pro-inflammatory cytokines together with markers of increased metabolic activity were highest in the peri-ovulatory phase. COH resulted in significantly altered cytokine profiles and specifically the cytokine inter-relationships were affected. Following COH, high-grade PBF positively predicted normal fertilisation and clinical pregnancy. High levels of a pro-angiogenic cytokine combined with a high-grade PBF were predictive of greater oocyte maturity, whilst follicular antral volume was less predictive of maturity. Cytokines previously correlated with cytoplasmic and nuclear maturation were not found to represent follicular volume, and furthermore, mature oocytes derived from small follicles were found to have equal viability to those retrieved from larger follicles. The FF of various subfertility pathologies demonstrated distinct features. To conclude, the microenvironment of the follicle accommodates the needs of the maturing oocyte in a very complex and dynamic manner. Any deviation from the normal balance of cytokines either by stimulation with exogenous gonadotrophins or by pelvic pathology potentially impacts oocyte maturation and viability.