The role of anandamide in human folliculogenesis, implantation and early pregnacny

Plasma AEA levels were measured by ultra-performance liquid chromatography and mass-spectrometry throughout the menstrual cycle in healthy women both cross-sectionally and longitudinally. Plasma and follicular fluid (FF) AEA levels were also determined in women undergoing in-vitro fertilisation and embryo transfer (IVF-ET) and correlations between FF AEA and follicle size and oocyte maturity were undertaken. Plasma AEA levels were then measured in these women on the day of oocyte retrieval (OR), embryo transfer (ET) and at pregnancy test (PT) and comparisons made between pregnant and non-pregnant women and between those with viable pregnancies and those who had miscarried at 6 weeks. The relationship between plasma AEA and sex steroids in the stimulated cycles was also examined. AEA was found to be hormonally regulated, mainly by gonadotrophins and estradiol, and its highest levels were at ovulation and low at the implantation window in natural and stimulated cycles. The endocannabinoid system was localised in human ovary, FF AEA was associated with folliculogenesis, ovulation and oocyte maturity. ROC analysis indicated that a FF AEA concentration of 1.09 nM discriminated between mature and immature oocytes. In successful pregnancies a significant decline in plasma AEA levels from ovulation to the day of ET than a significant rise from the day of ET to the day of PT appeared to be important Plasma AEA levels were high at 4 and 5 weeks gestation and then significantly declined at 6 weeks gestation. These data may show the potential for using AEA as a biomarker test for oocyte assessment and to improve pregnancy outcomes in stimulated IVF/ICSI cycles.