Fluctuation in anandamide levels from ovulation to early pregnancy in in-vitro fertilization-embryo transfer women, and its hormonal regulation.
BACKGROUND
Low levels of plasma arachidonoylethanolamide (anandamide) (AEA) (<2 nM) are associated with a successful early pregnancy in the mouse, and are thought to be regulated by sex steroid hormones. A similar association in the human may exist, although it has never been studied. The objective of this study was to investigate plasma AEA concentrations from the time of ovulation to implantation in pregnant and non-pregnant women, and whether AEA is hormonally regulated.


METHODS
Women who had undergone IVF/ICSI-embryo transfer were divided into pregnant (n = 12) and non-pregnant (n = 12) groups, based on serum beta-hCG >5 IU at 4 weeks and a viable intrauterine singleton pregnancy confirmed by ultrasound at 6 weeks gestation. Blood samples for plasma AEA and sex steroid hormonal measurements were taken at the time of oocyte collection, embryo transfer and pregnancy test, and an extra sample was also taken from the pregnant group at the viability ultrasound scan.


RESULTS
In pregnant women, there was a significant initial decrease in plasma AEA levels from the day of oocyte retrieval to that of embryo transfer. In addition, in the viable pregnancy group, plasma AEA was high at 4 and 5 weeks gestation, and a decline was observed at 6 weeks gestation (P = 0.003). No correlations were seen between plasma AEA and serum estradiol (E2), progesterone (P4) or beta-hCG in pregnant women; however, there was a significant correlation between plasma AEA and E2 (P = 0.022), but not between plasma AEA and serum P4, in non-pregnant women.


CONCLUSIONS
Our observations suggest that in successful pregnancy, a higher plasma AEA level at ovulation and a significantly lower level during implantation are required. The drop in AEA levels could be used as a biomarker for the appropriate timing of embryo transfer.
Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, PO Box 65, Leicester, Leicestershire LE2 7LX, UK.
Mona R
MR
El-Talatini
Anthony H
AH
Taylor
Justin C
JC
Konje
D000328:Adult; D001095:Arachidonic Acids / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D010064:Embryo Implantation / Q000502:physiology*; D004624:Embryo Transfer; D063388:Endocannabinoids; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D010060:Ovulation; D053284:Polyunsaturated Alkamides / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D011374:Progesterone / Q000097:blood; D020554:Sperm Injections, Intracytoplasmic
D001095:Arachidonic Acids; D018997:Chorionic Gonadotropin, beta Subunit, Human; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D011374:Progesterone; D004958:Estradiol; C078814:anandamide