Interleukin-2 Production in Whole Blood Cell Cultures of Women Undergoing Controlled Ovarian Hyperstimulation for Assisted Reproduction Technology Cycles
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).
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.
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.
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.
Available from: Raoul Orvieto
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ABSTRACT: The aim of the present study was to determine serum and follicular fluid C-reactive protein (CRP) levels in patients undergoing controlled ovarian hyperstimulation (COH) for IVF-embryo transfer cycle, and their possible correlation to COH variables.
The subjects were 16 consecutive patients undergoing our routine IVF long GnRH agonist protocol. Blood was drawn three times during the COH cycle: (i) the day on which adequate suppression was obtained (Day-S); (ii) the day of, or prior to HCG administration (Day-HCG); and (iii) the day of (and before) oocyte pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid CRP were compared among the three time points. Serum and follicular fluid CRP were measured with a commercial immunoturbidimetric assay.
Serum levels of CRP were significantly higher on Day-OPU and Day-HCG than on Day-S, and significantly higher on Day-OPU than on Day-HCG. No difference was observed between follicular and serum CRP levels on Day-OPU. No significant correlations were found between serum and follicular fluid CRP, or between serum CRP-to-BMI ratio and serum sex steroid levels or IVF treatment variables.
The significant increase in serum CRP levels during COH, especially after HCG administration, suggests that COH potentiates a state of systemic inflammation.
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ABSTRACT: To measure levels of serum P-selectin in patients undergoing controlled ovarian hyperstimulation (COH) cycles and to determine their possible correlation to COH variables.
Large university-based infertility and in vitro fertilization unit.
Fourteen consecutive patients undergoing our routine COH protocol for unexplained infertility. Interventions and
Blood was drawn three times during the COH cycle: (1) day 2 or 3 of the menstrual cycle, before gonadotropin treatment (Day-0); (2) day of or prior to human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) day of ovulation (Day-OVU). Serum levels of sex steroids and P-selectin were compared among the three time points. P-selectin was measured with a commercial quantitative sandwich immunoassay technique. To reduce interpatient variability, the percent difference between the Day-0 (non-stimulated, basal) level and the Day-hCG and Day-OVU levels was calculated.
P-selectin level on Day-hCG was significantly higher than on Day-0 (P < 0.05) and non-significantly higher than on Day-OVU (P < 0.12). No significant correlations were observed between serum P-selectin and patient age, amount of gonadotropins used, or estradiol or progesterone level.
The increase in serum P-selectin level during COH until peak estradiol suggests that COH may potentiate a state of platelet activation which is substantially attenuated after hCG administration.
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ABSTRACT: Controlled ovarian hyperstimulation (COH) is apparently a key factor in the success of in vitro fertilization-embryo transfer. One of the major complications of COH is severe ovarian hyperstimulation syndrome (OHSS), which may be attributable to a massive increase in systemic inflammatory cytokines or to neutrophil activation. The aim of the present review was to investigate the role of COH in the induction of an inflammatory response.
Major studies that have reported on the association between COH and inflammation were identified through MEDLINE searches and the published literature.
Several inflammatory mediators, namely, C-reactive protein and leukocyte and endothelial selectins, showed a significant increase after human chorionic gonadotropin (hCG) administration in vivo, reflecting an inflammatory state, and neutrophil and endothelial activation, respectively. On the other hand, hCG showed a direct depressive effect on mononuclear cells in vitro. Because the development of OHSS almost always follows hCG administration, the negative effect of hCG on peripheral mononuclear cells indicates that it probably causes OHSS by an indirect mechanism.
We suspect that hCG stimulates the ovaries to produce and secrete a still unknown intermediate factor, which in turn activates inflammatory processes that may lead to an increase in capillary permeability.
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