Follicular Fluid Insulin-like Growth Factor-I and Insulin-like Growth Factor–Binding Protein-1 and -3 Vary as a Function of Ovarian Reserve and Ovarian Stimulation
- 47 Downloads
Purpose: Follicular fluid concentrations of insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (BP)-1, and IGFBP-3 in 57 women undergoing in vitro fertilization and embryo transfer were examined to determine whether levels reflected differences in patients' exposure to gonadotropin stimulation and a diminished ovarian reserve.
Methods: Preovulatory follicular fluid was obtained from both gonadotropin-stimulated and unstimulated cycles. Subjects were grouped according to normal or decreased ovarian reserve and whether or not they received gonadotropin stimulation.
Results: The mean follicular fluid concentrations of IGF-I and IGFBP-1 were significantly lower in the “decreased” ovarian reserve group compared with the “normal” ovarian reserve group, with no change in estradiol or IGF-II levels. This resulted in a decreased molar IGF-I: BP ratio and an increased molar IGF-II:IGFBP-1 ratio. In unstimulated cycles, mean follicular fluid concentrations of IGFs did not differ significantly compared with those in stimulated cycles, whereas concentrations of IGFBP-1 and IGFBP-3 were significantly lower, leading to higher molar ratios of the IGFs to the binding proteins.
Conclusions: Follicular fluid IGF and binding proteins vary as a function of ovarian reserve and gonadotropin stimulation. This may reflect either differences in oocyte quality or a suboptimal follicular fluid environment.
Unable to display preview. Download preview PDF.
- 1.Palermo GD, Munne S, Colomberg CT, Cohen J, Rosenwaks Z: Genetics of abnormal human fertilization. Hum Reprod 1995;10:120–127Google Scholar
- 2.Paulson RJ, Sauer MV, Lobo RA: Embryo implantation after human in vitro fertilization: Importance of endometrial receptivity. Fertil Steril 1990;53:870–874Google Scholar
- 3.Rogers PAW, Milne BJ, Trounson AO: A model to show human receptivity and embryo viability following ovarian stimulation for in vitro fertilization. J In Vitro Fert Embryo Transfer 1986;3:93–98Google Scholar
- 4.Geisthoevel F, Moretti-Rojas IM, Rojas FJ, Asch RH: Immunoreactive insulin-like growth factor I in human follicular fluid. Hum Reprod 1989;4:35–38Google Scholar
- 5.Adashi EY, Resnick CE, D'Ercole JS, Svoboda ME, Van Wyk JJ: Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocrine Rev 1985;6:400–420Google Scholar
- 6.Hamori M, Blum WF, Torok A, et al.: Insulin-like growth factors and their binding proteins in human follicular fluid. Hum Reprod 1991;6:313–318Google Scholar
- 7.Baxter RC, Martin JL: Radioimmunoassay of growth hormone-dependent insulin-like growth factor binding protein in human plasma. J Clin Invest 1986;78:1504–1512Google Scholar
- 8.Giudice LC: Insulin-like growth factors and ovarian follicular development. Endocrine Rev 1992;13:641–669Google Scholar
- 9.Lee P, Conover CA, Powell DR: Regulation and function of insulin-like growth factor binding protein-1. Proc Soc Exp Biol Med 1993;204:4–29Google Scholar
- 10.El-Roeiy A, Chen X, Roberts VJ, LeRoith D, Roberts CT Jr, Yen SSC: Expression of insulin-like growth factor-I (IGF-I) and IGF II and the IGF-I, IGF-II, and insulin receptor genes and localization of the gene products is in the human ovary. J Clin Endocrinol Metab 1993;77:1411–1418Google Scholar
- 11.El-Roeiy A, Chen X, Roberts VJ, et al.: Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries. J Clin Endocrinol Metab 1994;78:1488–1496Google Scholar
- 12.Eden JA, Jones J, Carter GD, Alaghband-Zadeh J: A comparison of follicular fluid levels of insulin-like growth factor-I in normal dominant and cohort follicles, polycystic and multicystic ovaries. Clin Endocrinol (Oxf) 1988;29:327–336Google Scholar
- 13.Van Dessel HJ, Chandrasekher YA, Yap OW, Lee PD, Hintz RL, Faessen GH, Braatt DD, Fauser BC, Giudice LC: Serum and Follicular fluid levels of insulin-like growth factor-I (IGF-I) IGF-II and IGF-binding protein-1 and-3 during the normal menstrual cycle. J Clin Endocrinol Metab 1996;81:122–126Google Scholar
- 14.Zhou J, Dsupin BA, Giudice LC, Bondy CA: Insulin-like growth factor system gene expression in human endometrium during the menstrual cycle. J Clin Endocrinol Metab 1994;79:1723–1734Google Scholar
- 15.Dor J, Ben-Shlomo I, Lunenfeld B, et al.: Insulin-like growth factor-I (IGF-I) may not be essential for ovarian follicular development: Evidence from IGF-I deficiency: J Clin Endocrinol Metab 1992;74:539–542Google Scholar
- 16.Jimena P, Castilla JA, Peran F, Molina, R, Ramirez JP, Acebal M, Vergara, F, Herruzo A: Insulin and insulin-like growth factor I in follicular fluid after induction of ovulation in women undergoing in vitro fertilization. J Reprod Fertil 1992;96:641–647Google Scholar
- 17.Artini PG, Battaglia C, D'Ambrogio G, Barreca, A, Droghini F, Volpe A, Genazzani AR: Relationship between human oocyte maturity, fertilization and follicular fluid growth factors. Hum Reprod 1994;9:902–906Google Scholar
- 18.Klein NA, Battaglia DE, Miller PB, Branigan EF, Giudice LC, Soules MR: Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age. J Clin Endocrinol Metab 1996;81:1946–1951Google Scholar
- 19.Seifer DB, Giudice LC, Dsupin, BA, Haning RV Jr, Frishman GN, Burger HG: Follicular fluid insulin-like growth factor-I and insulin-like growth factor-II concentrations vary as a function of day 3 serum follicle stimulating hormone. Hum Reprod 1995;10:804–806Google Scholar
- 20.Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeiseel HHJ, Bierich J: A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: Its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 1990;70:1292–1298Google Scholar
- 21.Juul A, Main K, Blum W, Lindholm J, Ranke M, Skakkebaek, N: The ratio between serum levels of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol 1994;41:85–93Google Scholar
- 22.Ibrahim ZH, Matson PL, Buck P, et al.: The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response. Fertil Steril 1991;55:202–204Google Scholar
- 23.Owen EJ, Shoham Z, Mason BA, et al.: Cotreatment with growth hormone, after pituitary suppression, for ovarian stimulation in vitro fertilization: a randomized, double-blind, placebo-control trial. Fertil Steril 1991;56:1104–1110Google Scholar
- 24.Hughes SM, Huang ZH, Morris ID, et al.: A double-blind cross-over controlled study to evaluate the effect of human biosynthetic growth hormone on ovarian stimulation in previous poor responders to in-vitro fertilization. Hum Reprod 1994;9:13–18Google Scholar
- 25.Bergh C, Hillensjo T, Wildand M, et al.: Adjuvant growth hormone treatment during in vitro fertilization: A randomized, placebo-controlled study. Fertil Steril 1994;62:113–201Google Scholar
- 26.Dor J, Sidman DS, Amudai E, et al.: Adjuvant growth hormone therapy in poor responders to in-vitro fertilization: Prospective randomized placebo-controlled double-blind study. Hum Reprod 1995;10:40–43Google Scholar
- 27.Conover CA, Powell DR: Insulin-like growth factor (IGF)-binding protein-3 blocks IGF-I-induced receptor down regulation and cell desensitization in cultured bovine fibroblasts. Endocrinology 1991;129:710–716Google Scholar
- 28.Eglin RG, Busby WH, Clemmons DR: An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Proc Natl Acad Sci USA 1988;4:3254–3259Google Scholar
- 29.Cataldo NA, Giudice LC: Insulin-like growth factor binding protein profiles in human ovarian follicular fluid correlate with follicular functional status. J Clin Endocrinol Metab 1992;74:821–829Google Scholar
- 30.Jones JL, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocrine Rev 1995:16:3–34Google Scholar
- 31.Hill DJ: Growth factors and the endocrine system. J Endocrinol 1987;115(Suppl):3Google Scholar