Hum. Reprod. Advance Access published online on April 10, 2009
Human Reproduction, doi:10.1093/humrep/dep065
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Fluctuation in anandamide levels from ovulation to early pregnancy in in-vitro fertilization-embryo transfer women, and its hormonal regulation
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
1 Correspondence address. Endocannabinoid Research Group, Reproductive Sciences Section, University of Leicester, Leicester Royal Infirmary, Robert Kilpatrick Clinical Sciences Building, PO Box 65, Leicester, Leicestershire LE2 7LX, UK. Tel: +44-116-252-5826; Fax: +44-116-252-5846; E-mail: jck4{at}le.ac.uk
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 β-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 β-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.
Conclusion: 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.
Key words: anandamide/in-vitro fertilization/implantation/estradiol/progesterone
Submitted on November 28, 2008; resubmitted on January 20, 2009; accepted on February 18, 2009.