Interleukin-2 production in whole blood cell cultures of women undergoing controlled ovarian hyperstimulation for assisted reproduction technology cycles

PROBLEM: To determine whether human chorionic gonadotropin (hCG) modulates the in vitro release of interleukin (IL-2) from human peripheral lymphocytes and monocytes derived from patients undergoing controlled ovarian hyperstimulation (COH). METHOD OF STUDY: A large university-based IVF unit was used for the study. Blood was drawn thrice from 12 women undergoing our routine IVF long gonadotropin-releasing-hormone-analog protocol during the COH cycle: (1) day on which adequate suppression was obtained (Day-S); (2) day of or prior to hCG administration (Day-hCG); and (3) day of ovum pick-up (Day-OPU). At each point of time, blood was tested for sex-steroid levels and then cultured for 72 hr either without (control-culture) or with hCG (hCG-culture) or with mitogenic stimulation by phytohemagglutinin (PHA-culture). The culture-medium supernatants were tested for IL-2 levels with a commercial sandwich enzyme-linked immunoassay. RESULTS: Whole blood culture IL-2 levels increased significantly during COH until peak E2, and then decreased significantly after hCG administration. IL-2 levels were decreased in the control- and PHA-culture media on Day-OPU compared with Day-hCG. There were no significant correlations between IL-2 levels in the culture media and serum estradiol, progesterone or human chorionic gonadotropin levels. CONCLUSION: Apparently, hCG attenuates IL-2 production by mononuclear cells with and without mitogenic stimulation, irrespective of the estradiol level. This suggests that hCG may indirectly modulate the inflammatory response, resulting in the ovarian hyperstimulation syndrome.