Interleukin-2 production in whole blood cell cultures of women undergoing controlled ovarian hyperstimulation for assisted reproduction technology cycles
ABSTRACT 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.
SourceAvailable from: Raoul Orvieto[Show abstract] [Hide abstract]
ABSTRACT: Background Ovarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargement and acute third space fluid sequestration that almost always develops after hCG administration or in early pregnancy. OHSS is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines. In the present pilot exploratory case series, we sought to evaluate interleukin (IL)-2 and suppressor of cytokine signaling (SOCS)-1 expressions in the peripheral blood mononuclear cells (PBMCs) of patients suffering from severe ovarian hypertimulation syndrome (OHSS), and to examine whether their expressions differ when compared to PBMCs originated from normal early pregnant women (without OHSS).Methods Interleukin-2 and SOCS-1 mRNA expressions were examined in PBMCs of 5 women who were hospitalized due to severe OHSS (OHSS group) and 5 women with early IVF pregnancies and without OHSS (control group).ResultsInterleukin-2 mRNA levels in PBMCs were significantly higher in the OHSS as compared to the control groups. Moreover, while SOCS-1 mRNA levels were non-significantly lower, the ratio between IL-2 and SOCS-1 mRNA levels was significantly higher in the OHSS, as compared to the control group.Conclusions The inflammatory response to hCG, leading to dysregulation of Il-2 expression and SOCS activation, might be the culprit of OHSS. Additional large prospective studies are required to elucidate the effect of hCG on patients¿ inherited inflammatory cascades, which may help discriminating those at risk to develop severe OHSS from those who are not.Journal of Ovarian Research 11/2014; 7(1):106. DOI:10.1186/s13048-014-0106-2 · 2.03 Impact Factor
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ABSTRACT: Aims: To evaluate the incidence of pericardial irritation in females after hormonal stimulation in in vitro fertilization program, and to set its clinical significance as a symptom of ovarian hyperstimulation syndrome (OHSS). Patients: Thirty-nine females, aged 30 ± 5 years (20–46), with a normal echo finding prior to hormonal stimulation. Methods: Serial echocardiography: baseline A, in hCG application B, embryotransfer C. Results: Thirty-nine, 39, and 35 echocardiography examinations were done on A, B, and C respectively. On B, in 7 (17.9%) of 39 patients either new pericardial effusion “1,” increased pericardial echogenity “2,” or both “3” were detected (4 patients, 2 patients, and 1 patient, i.e., 10.3%, 5.1%, and 2.6% respectively.). On C, in 8 of 35 patients (22.8 %) abnormalities were detected: “1” in 2 patients (5.7 %), “2” in 1 patient (2.9 %), and “3” in 5 patients (14.2 %). No clinical symptoms related to these findings were present. No OHSS occurred in these patients. On the contrary, clinical OHSS developed later in 2 patients, classified as medium degree (1 patient) and severe degree (1 patient)—both patients had negative echo during follow-up. Conclusion: Echocardiographic signs of mild pericardial irritation may appear also in patients with no clinical signs of OHSS. The incidence of these changes increases during stimulation procedure. Development of OHSS may not be preceded by the incidence of these warning signs. Consequently, routine echocardiographic examination during stimulation is not indicated, since significant pericardial effusion is rather a late sign of OHSS.Echocardiography 09/2006; 23(9):729 - 733. DOI:10.1111/j.1540-8175.2006.00302.x · 1.25 Impact Factor
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ABSTRACT: To establish correlations between laboratory findings and clinical symptoms of moderate and severe ovarian hyperstimulation syndrome (OHSS). A retrospective study. Department of obstetrics and gynecology, public clinical hospital. Nineteen women admitted to the public hospital with a diagnosis of OHSS. The procedure of controlled ovarian stimulation (COH) was performed in the private assisted reproductive technology centre. Blood samples were collected, ultrasound examination of ovaries, abdominal circumference measurement were performed, intravenous crystalloids, plasma expanders such colloids and albumin were given. Correlations between mean laboratory results (haematocrit, c-reactive protein (CRP), white blood count, serum protein, serum albumin), ovarian size in ultrasound examination, abdominal circumference, and amount of albumin and hydroxyethyl starch transfused to the patient were assessed. Significant correlation was observed between CRP concentration and abdominal circumference measured when the patient was admitted to the department, between CRP concentration and ovarian size measured during ultrasound examination at admission and between CRP concentration and body weight. CRP can be a potential candidate to an indicator of OHSS severity.Gynecological Endocrinology 02/2010; 26(6):399-403. DOI:10.3109/09513591003632266 · 1.14 Impact Factor