Comparison of follicular fluid insulin-like growth factor II and insulin-like growth factor binding protein 4 levels between short 7-day and long gonadotropin-releasing hormone agonist protocols

Abstract

OBJECTIVE: Insulin-like growth factor II (IGF-II) and Insulin-like growth factor binding protein 4 (IGFBP-4) play a major role in the autocrine and paracrine regulation of folliculogenesis. To explore the individual influence on the intrafollicular microenvironment between the short 7-day gonadotropin-releasing hormone agonist (GnRHa) protocol (7-day protocol) and GnRHa long protocol (long protocol) by comparing the concentrations of IGF-II, IGFBP-4, and the ratio of IGF-II/IGFBP-4 in follicular fluid. DESIGN: Prospective randomized controlled study. MATERIALS AND METHODS: 88 infertile patients with tubal factor who accepted IVF treatment from July to October 2007 were included in this study. 7-day protocol group (n=44): GnRHa (decapeptyl, Ferring) was injected 0.1 mg daily from day 2 of the menstrual cycle to day 8. At the same time gonadotropin (Gn) was injected daily from day 3. Long protocol group (n=44): GnRHa (diphereline, Ferring) was injected 1.88 mg singly in the mid-luteal phase of previous menstrual cycle. Once the patient was down regulated, gonadotropin injection was started. Follicular fluid was obtained from dominant follicles during oocyte retrieval. The levels of IGF-II and IGFBP-4 in follicular fluid were detected separately by radioimmunoassay and enzyme-linked immunosorbent assay. RESULTS: The durations of controlled ovarian stimulation was significantly shorter and total dose of Gn used were significantly lower in the 7-day protocol group. The levels of serum E2 and E2 per mature follicle on the day of hCG injection, the number of oocytes retrieved, fertilization rate, cleaved embryos rate, top-quality embryos rate, implantation rate, pregnancy rate, and clinical abortion rate were similar between the two groups. The concentrations of IGF-II (0.17±0.06ng/ml vs 0.20±0.07 ng/ml, P=0.020) and IGFBP-4 (2915.48±1443.02pg/ml vs 3646.64±1818.67pg/ml, P=0.040) in follicular fluid of the 7-day protocol group patients were significantly lower. There was no significant difference in the ratio of IGF-II/IGFBP-4 (0.07±0.04 vs 0.07±0.03, P=0.471) between the 7-day and long protocol group. Linear correlation analysis showed that the level of follicular fluid IGF-II was positively correlated to total dose of Gn used (r=0.316, P <0.05). CONCLUSIONS: The short 7-day and long GnRHa protocols may affect the concentrations of follicular fluid IGF-II and IGFBP-4. However, the changes of follicular fluid IGF-II and IGFBP-4 concentrations may not contribute to different clinical outcomes.