Vascular endothelial growth factor in serum and in the follicular fluid of patients undergoing hormonal stimulation for in-vitro fertilization.

A cross-sectional study regarding endocrine and cytokine parameters in human follicular fluid (FF) as compared to serum values following hormonal stimulation for in-vitro fertilization was conducted. The patients (n = 32) were treated sequentially with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin followed by a combination of buserelin plus highly purified follicle stimulating hormone and finally human chorionic gonadotrophin, in order to induce ovulation. The FF content of pro-inflammatory (IL-1, IL-6), and anti-inflammatory (IL-1ra, IL-10) cytokines, of the immune response-related soluble interleukin-2 receptor (sIL-2R), as well as the mitogens vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) were determined. Routine evaluation included peripheral blood cell counts, morphological data of the ovary and ova, ovarian steroids, prolactin concentrations and thyroid function parameters [free thyroxine (fT4), thyroglobulin]. The concentrations of IL-6, IL1-ra, sIL-2R, VEGF and bFGF in the FF compartment were higher than in serum in the majority of cases. Regression analysis showed a significant association between the serum and FF concentrations of fT4 (P = 0.04; y = 0.37 + 0.34x) and IL-6 (P = 0.002; y = 0.78 + 0.5x). Multiple regression analysis revealed that progesterone played a role in determining VEGF concentrations in the FF (P = 0.07; y = 0.37 + 0.86x). Thyroglobulin concentrations within the FF were extremely low, whereas fT4 concentrations in the FF were similar to those in serum. Patients with a previously diagnosed hypothyroidism tended to have lower serum oestradiol and higher serum progesterone when compared to euthyroids. We conclude that the human FF represents a functional compartment that integrates endocrine, immunological, and mitogenic signalling that is unique for each ovarian follicle. The close association between progesterone and VEGF within the FF suggests a close association of this mitogen to gonadotrophin stimulation, confirming the ovary as a production site of VEGF.

Spontaneous abortion and psychosomatics. A prospective study on the impact of psychological factors as a cause for recurrent spontaneous abortion.

A group of 36 patients who had had at least two consecutive spontaneous abortions and who desired to have children was subjected to a psychosomatic investigation before a biomedical diagnostic screening programme was started. A semi-structured interview regarding sociodemographic data, current relationship, social support, education, occupation and medical anamnesis was carried out. In addition, all women completed four standardized questionnaires on the topics of anxiety, somatization disorder, life satisfaction and depression. A control group of 36 women, matched for age and occupation, was subjected to the same psychosomatic investigation. The findings of the diagnostic screening programme showed that 16 women had abortions because of physical abnormality, and 15 women had no physically confirmed cause (in five women, the investigations were not completed). Following recurrent spontaneous abortion, 18 women had a successful pregnancy within 2 years, and 18 women were still childless. The comparison between patients and the control group revealed that patients with recurrent abortion were significantly more satisfied with their life quality regarding leisure time, financial situation and occupation. No significant differences were observed in any other variables. Patients who suffered spontaneous abortions due to a physical disorder showed partner relationship of longer duration, and more frequent miscarriages. Women with successful pregnancy within 2 years after recurrent miscarriage were significantly younger and had fewer physically related abortions compared with women who remained childless. In summary, psychological factors seem to be of subordinate importance as a cause for recurrent spontaneous abortion. Moreover, physical abnormalities in the reproductive system have a predominant impact on the prediction of a future successful pregnancy.

Perspectives on ovarian dysfunction and autoimmunity.

Recent research has documented the fact that a series of factors appear to play an important role during early phases of ovarian formation and function. Within the field of reproductive medicine some of the areas of future research will encompass genetical aspects, the influence of local regulatory growth factors, the role of innervation, the role of the resident immune cells, and the potential role of hCG. The influence of these factors can be studied in animal models.

A new endocrinological and immunological syndrome in SLE: elevation of human chorionic gonadotropin and of antibodies directed against ovary and endometrium antigens.

We have analysed the levels of gonadotropins in male and female patients with systemic lupus erythematosus (SLE). Human chorionic gonadotropin hCG was elevated in 23.8% of patients compared with 12.7% of controls. hCG isolated from the serum of SLE patients was bioactive in vitro. Levels of hCG were significantly correlated with those of its beta-subunit but not with the levels of follicle stimulating hormone, luteinizing hormone, prolactin alphafetoprotein or carcino embryonic antigen. A high percentage of patients presented an organ-specific humoral immune response against ovarian (26.7%) and endometrial (40%) antigens compared with controls (8% and 7.6%, respectively). Endometrial antibodies were significantly correlated to the levels of prolactin. The ovarian tumour marker CA-125 was elevated in 32.5% of patients, including two males. As a whole, these elements delineate a new endocrine and immunological syndrome in SLE in which the elevation of hCG could provide a central physiological explanation for a series of endocrine alterations that characterize this disease.

Autoimmunity and the ovary.

The ovary was first documented as a target of autoimmunity over three decades ago yet today the aetiology and pathogenesis of autoimmune-mediated premature ovarian failure (POF) are poorly understood. Here, Roy and Helga Moncayo provide a brief overview of human autoimmune-mediated POF and the animal models of POF. They propose a model for the development of the disease, highlighting the role of supraphysiological levels of gonadotropins in inducing selectively antigenic mature ovarian elements.