Intrauterine microdialysis reveals cycle-dependent regulation of endometrial insulin-like growth factor binding protein-1 secretion by human chorionic gonadotropin.

OBJECTIVE: To investigate whether hCG may directly influence endometrial differentiation and function. DESIGN: Controlled clinical study. SETTING: Tertiary university center. PATIENT(S): Fifty-six women with infertility. INTERVENTION(S): An intrauterine microdialysis device (IUMD) was developed that consisted of two balloon catheters connected by microdialysis tubing (molecular weight cutoff: 2,000 kDa). The IUMD was inserted into the uterine cavity and perfused with saline for 3 hours. In 45 women, urinary hCG was then added for 5 hours. Eleven women underwent an identical procedure but without the application of hCG. MAIN OUTCOME MEASURE(S): The response of the endometrium was assessed by measuring IGFBP-1 in the perfusate. RESULT(S): Intrauterine secretion of IGFBP-1 was strictly confined to the late secretory phase (>or=10 days after the beginning of the LH peak). This time point marks the closing of the implantation window. The application of hCG did not affect intrauterine IGFBP-1 levels before day 10 but induced a significant decrease of intrauterine IGFBP-1 levels thereafter. There was no significant change of intrauterine IGFBP-1 levels in the controls. CONCLUSION(S): Intrauterine microdialysis allows a dynamic assessment of endometrial paracrine function in vivo. Human chorionic gonadotropin may be involved in the mechanisms regulating endometrial receptivity.

Cycle dependency of intrauterine vascular endothelial growth factor levels is correlated with decidualization and corpus luteum function.

OBJECTIVE: To determine intrauterine levels of vascular endothelial growth factor (VEGF)-A during the menstrual cycle in the human female and to investigate the impact of decidualization and corpus luteum function. DESIGN: Prospective clinical study. SETTING: Tertiary university center. PATIENT(S): Fifty-four women with infertility problems. INTERVENTION(S): Intrauterine concentrations of VEGF-A were determined at various time points during the secretory phase using a novel intrauterine microdialysis device. Concomitantly, intrauterine insulin-like growth factor binding protein (IGFBP)-1 levels served as a paracrine parameter for decidualization. Serum progesterone (P) and E(2) levels were determined as markers for corpus luteum function. Intrauterine VEGF levels. RESULT(S): The VEGF levels in utero were clearly cycle dependent with increasing levels during the late secretory and premenstrual phases. There was a significant correlation with the decidualization marker IGFBP-1. In contrast, intrauterine VEGF levels showed a significant negative correlation with serum E(2) and P. CONCLUSION(S): Intrauterine VEGF levels are regulated in a cycle-dependent way. Increasing levels in the late secretory phase are clearly correlated with decidualization. In contrast, decreasing serum levels of steroids produced by the regressing corpus luteum are less likely to be responsible for increasing VEGF levels in the premenstrual phase.