Evaluation des Sexualhormon-bindenden Globulins in humaner Follikelflüssigkeit im Rahmen der Pilotstudie „Explorative biochemische Analyse aktueller Biomarker in humaner Follikelflüssigkeit und deren Einfluss auf die Befruchtungsrate in der assistierten Reproduktion“

Over the last decades the idea has been established that biomarkers in the ovarian follicular fluid can predict in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. Sex hormone-binding globulin (SHBG) could be a candidate, as an important role in the local regulation of ovarian function is presumed. The aim of this thesis was to generate hypotheses about the relationships between the follicular fluid SHBG concentration and the follicle characteristics oocyte retrieval and follicle size, IVF and ICSI parameters like follicle and oocyte counts, fertilisation rate, the occurrence of a pregnancy or live birth, and the sociodemographic and clinical parameters age and body mass index (BMI). For comparison, these relationships should also be examined with the serum SHBG concentration on oocyte retrieval day. Moreover, it should be examined whether the dispersion of the SHBG concentrations of the follicles from a patient is associated with some of those parameters. A prospective, explorative cohort study was carried out at the competence centre of reproductive medicine in Marburg. A total of 327 follicular fluid samples of individually separated follicles from 54 patients undergoing IVF or ICSI treatment was analysed. Statistical analysis was orientative, without adjustment for multiple testing. SHBG was significantly lower concentrated in follicular fluid than in serum. Its passage into the follicle seems to be partially inhibited. The SHBG concentrations in follicular fluid and serum correlated significantly and strongly positively. This indicates that SHBG in follicular fluid largely derives from the bloodstream, while intrafollicular SHBG synthesis has a lesser impact on the follicular fluid level. No marked difference of the SHBG level between follicles without and with retrieved oocyte was found. Thus, there was no indication that SHBG plays a relevant role in the process of cumulus-oocyte complex detachment. In small (< 16 mm) follicles, the SHBG concentration was higher than in large (≥ 16 mm) follicles. The difference narrowly missed statistical significance (p = 0,055). Interestingly, the follicular fluid SHBG level showed a significant moderate positive correlation with several of the IVF and ICSI parameters: the number of punctured follicles, of retrieved and of mature oocytes, the rate of mature oocytes, the number of correctly fertilised oocytes and the fertilisation rate. Solely with the fertilisation rate, the serum SHBG level showed a lower and not significant correlation. Thus, the follicular fluid level in particular could be predictive of it. Therefore, SHBG in follicular fluid should be considered as a candidate for a biomarker of successful IVF and ICSI treatment outcomes. However, its predictive ability did not reach as far as the occurrence of pregnancy or live birth. No relevant difference of the SHBG levels between patients without and with pregnancy, or live birth, was observed. Conversely, two previous studies reported signifcantly higher follicular fluid SHBG levels in women who subsequently conceived. This association may exist solely for a particular constellation of follicle profiles, causes of infertility and treatment protocols. The SHBG level did not correlate with age. It should be noted that the examination was limited to an age span from 25 to 47 years. A significant moderate negative correlation between follicular fluid SHBG level and BMI was found. This is interesting, as overweight negatively impacts fertility and IVF and ICSI treatment outcomes. The existence of a negative correlation with BMI and a positive correlation with several successful treatment parameters seems to be consistent. None of the examined parameters showed an association with the dispersion of the SHBG concentrations of the follicles from the patient. The study results contribute a piece to the mosaic of the knowledge about follicular fluid constituents and their association with various parameters. Eventually, to confirm the study results including the significant ones, further studies that allow to make statements about the population using inferential statistics are needed.