THE IMPACT OF HMG ON FOLLICULAR FLUID HORMONE LEVELS, EMBRYO QUALITY AND IVF OUTCOME

Abstract

The objective of this study is to evaluate the effect of HMG on the follicular fluid hormone levels, embryo quality and IVF outcomes when added at different times of stimulation to rFSH in a long protocol. Seventy infertile women were randomized into three groups; group 1(n=23) was stimulated only with rFSH; whereas, HMG was added from the beginning (group 2, n=23) or when a 10 mm follicle developed (group 3, n=24). Follicular fluid hormone levels, day 3 embryo quality, implantation and clinical pregnancy rates were assessed. The number of grade 1 embryos, and estradiol/progesterone ratio were significantly higher in group 2 compared to group 1. The numbers of grade 2 and 3 embryos, and day 3 embryos with less than 5 cells were significantly higher in group 1. Clinical pregnancy rate was significantly higher in group 2 than group 1. In conclusion, HMG supplementation to rFSH does not increase the number of oocytes retrieved, the numbers of day 3 embryos and day 3 embryos at 8-cell or more stages of development, fertilization and implantation rates. HMG supplementation from the beginning of rFSH stimulation result in improvement of clinical pregnancy rates and other indices of embryo quality such as embryo grading.

Keywords

• Gonadotropins, follicular fluid, embryo quality, IVF/ICSI outcome, FSH

Kaynakça

1. Fevold HL: Synergism of follicle stimulating and luteinizing hormones in producing estrogen secretion. Endocrinology. 1941; 28: 33-36.
2. Hillier SG, Whitelaw PF, Smyth CD. Follicular oestrogen synthesis: the 'two-cell, two-gonadotrophin' model revisited. Mol Cell Endocrinol 1994; 100: 51
3. Lévy DP, Navarro JM, Schattman GL, Davis OK, Rosenwaks Z. The role of LH in ovarian stimulation: exogenous LH: let's design the future. Hum Reprod 2000; 15: 2258-2265.
4. Tesarik J, Mendoza C. Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod 2002; 17: 3129-3137.
5. Huddleston HG, Jackson KV, Doyle JO, Racowsky C. hMG increases the yield of mature oocytes and excellent-quality embryos in patients with a previous cycle having a high incidence of oocyte immaturity. Fertil Steril 2009; 92: 946-949
6. Filicori M. The role of luteinizing hormone in folliculogenesis and ovulation induction. Fertil Steril 1999; 71: 405-414.
7. Schoot DC, Harlin J, Shoham Z, et al. Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women. Hum Reprod 1994; 9: 1237-1242.
8. Filicori M, Cognigni GE, Taraborrelli S, et al. Luteinizing hormone activity supplementation enhances follicle-stimulating hormone efficacy and improves ovulation induction outcome. J Clin Endocrinol Metab 1999; 84: 2659-2663.

9. Humaidan P, Bungum M, Bungum L, Yding Andersen C. Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study. Reprod Biomed Online 2004; 8: 635-643.
10. Platteau P, Smitz J, Albano C, et al. Exogenous luteinizing hormone activity may influence the treatment outcome in in vitro fertilization but not in intracytoplasmic sperm injection cycles. Fertil Steril 2004; 81: 1401-1404.
11. Wiener-Megnazi Z, Vardi L, Lissak A, et al. Oxidative stress indices in follicular fluid as measured by the thermochemiluminescence assay correlate with outcome parameters in in vitro fertilization. Fertil Steril 2004; 82: 1171-1176.
12. Costa LO, Mendes MC, Ferriani RA, et al. Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes. raz J Med Biol Res 2004; 37: 1747-1755.
13. Muñoz J, Herreros J, Garijo E, Galera F. Intrafollicular microenvironment as embryo quality predictor. Fertility and Sterility 2008; 90: 475.
14. Smitz J, Andersen AN, Devroey P, Arce JC; MERIT Group. Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod 2007; 22: 676-687.
15. Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod 2006; 21: 3217-3227.
16. Balaban B, Yakin K, Urman B. Randomized comparison of two different blastocyst grading systems. Fertil Steril 2006; 85: 559-563.
17. Strehler E, Abt M, El-Danasouri I, De Santo M, Sterzik K. Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. Fertil Steril 2001; 75: 3323
18. Weghofer A, Munné S, Brannath W, et al. The impact of LH-containing gonadotropins on diploidy rates in preimplantation embryos: long protocol stimulation. Hum Reprod 2008; 23: 499-503.
19. Platteau P, Nyboe Andersen A, Loft A, et al. Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles. Reprod Biomed Online 2008; 17: 190-198.
20. Fábregues F, Creus M, Peñarrubia J, et al. Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age. Fertil Steril 2006; 85: 925-9
21. Hompes PG, Broekmans FJ, Hoozemans DA, Schats R; FIRM group. Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization-intracytoplasmic sperm injection patients. Fertil Steril 2008; 89: 1685-1693.
22. Coomarasamy A, Afnan M, Cheema D, et al. Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long downregulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis. Hum Reprod 2008; 23: 310-315.
23. Paterson ND, Foong SC, Greene CA. Improved pregnancy rates with luteinizing hormone supplementation in patients undergoing ovarian stimulation for IVF. J Assist Reprod Genet 2012; 29: 579-5
24. Xia P, Younglai EV. Relationship between steroid concentrations in ovarian follicular fluid and oocyte morphology in patients undergoing intracytoplasmic sperm injection (ICSI) treatment. J Reprod Fertil 2000; 118: 229-233.
25. Fried G, Wramsby H, Tally M. Transforming growth factor-beta1, insulin-like growth factors, and insulinlike growth factor binding proteins in ovarian follicular fluid are differentially regulated by the type of ovarian hyperstimulation used for in vitro fertilization. Fertil Steril 1998; 70: 129-134.
26. Fournet N, Weitsman SR, Zachow RJ, Magoffin DA. Transforming growth factor-beta inhibits ovarian 17 alpha-hydroxylase activity by a direct noncompetitive mechanism. Endocrinology 1996; 137: 166-174.