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Serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations were measured at the end of the proliferative phase in infertility patients undergoing normal menstrual cycle frozen embryo transfer, exogenous hormone-supported frozen embryo transfer and in-vitro fertilization (IVF) treatment cycles. These patients were divided into five groups according to their ovarian follicular activity. The exogenous hormone-supported frozen embryo transfer group, who had no ovarian follicles, and the IVF groups (number of follicles ranging from 4-38) showed statistically higher serum IGFBP-1 concentrations when compared to the normal menstrual cycle group (Por = 0.01). There was no significant difference in the serum IGFBP-1 concentrations between the exogenous hormone support frozen embryo transfer group and the poor or normal response IVF groups (number of follicles ranging from 4 to 16). An IVF group that displayed an excessive response to our standard human menopausal gonadotrophin stimulation (20 mature follicles or oestradiol10,000 pmol/l) showed a significantly higher serum IGFBP-1 concentration when compared with the other groups (P = 0.001). This subgroup was subsequently given a modified (follicle-stimulating hormone) stimulation regime which resulted in a significant reduction in serum IGFBP-1 concentrations (P0.05). There was no correlation between serum oestradiol and IGFBP-1 overall or within the patient groups. We conclude that serum IGFBP-1 concentrations in our down-regulated assisted conception cycles did not increase in line with ovarian follicular activity, unless an excessive response was displayed.

This study investigated the development of functional ovarian cysts during pituitary down-regulation prior to in-vitro fertilization (IVF), and identified 16 cases of cysts in 288 IVF cycles studied. Comparing the patients with functional ovarian cysts to the other 272 IVF cycles, there was no significant difference in age or incidence of endometriosis but significantly (P < 0.01) more patients with cysts had ovulatory dysfunction. The serum progesterone was < 5.7 nmol/l in all 16 patients with cysts on day 4 of the IVF cycle, and in eight of these patients the serum progesterone was < 5.7 nmol/l on the day buserelin was commenced. In 10 of the 16 patients with cysts, serum oestradiol concentrations remained elevated despite the prolonged use of buserelin, and the cysts were aspirated. The aspirate in all cases was clear without any suggestion of endometriosis. The cyst aspirates had significantly lower progesterone (P < 0.001), higher androstenedione (P < 0.01) and similar oestradiol concentrations to 10 follicular fluid samples collected at the time of oocyte retrieval. This study suggests that functional ovarian cysts may develop during pituitary down-regulation, and these cysts are follicular cysts rather than persistent corpora lutea or endometriomata.

In primates, corpus luteum development involves both gonadotrophin stimulation and exposure to low density lipoprotein (LDL) delivered through vascularization of the granulosa cell-derived layer. These regulatory influences were modelled in vitro using granulosa cells obtained during in-vitro fertilization (IVF) cycles controlled with gonadotrophin releasing hormone (GnRH) analogue, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). Granulosa cells were cultured in defined medium on extracellular matrix. Without gonadotrophin or LDL in the medium, progesterone production declined progressively. With LDL alone, there was a short-lived elevation of progesterone output which subsequently declined. Culture with HCG alone resulted in a relatively unchanged rate of steroid production over 5 days despite morphological development. This contrasted with a marked and sustained increase in progesterone output over the same time when granulosa cells were cultured with combined HCG/LDL. Cultures were challenged with combined HCG/LDL on day 5. Where initial incubation included HCG, the challenge resulted in a recovery of progesterone output to values comparable to those of granulosa cells exposed to continuous HCG/LDL. Initial incubation without gonadotrophin led to a reduced response. Results suggest that LDL delivery to granulosa cells of the early corpus luteum causes a short-lived period of progesterone production. Sustained luteinization of granulosa cells and maintenance of gonadotrophin responsiveness requires continued exposure to gonadotrophin in the luteal phase.