Advertisement

Human choriogonadotropin prior to controlled ovarian stimulation and in vitro fertilization improves implantation, and pregnancy rates

  • Eduardo L. Motta
  • Gary D. Smith
  • Paulo C. Serafini
  • Marcio Coslovsky
  • Pericles Hassun
  • Andre M. Rocha
  • Isaac YadidEmail author
ASSISTED REPRODUCTION

Abstract

Purpose

Our purpose was to retrospectively compare controlled ovarian stimulation(COH) in IVF cycles with administration of hCG on the day of menses (D1-hCG) with women not receiving hCG at day 1 of menses (Control).

Methods

Data on maternal age, endocrine profile, amount of rFSH required, embryo characteristics, implantation and pregnancy rates were recorded for comparison between D1-hCG (n = 36) and Control (n = 64).

Results

Dose of rFSH required to accomplish COH was significantly lower in D1-hCG. Following ICSI, more top-quality embryos were available for transfer per patient in the D1-hCG and biochemical pregnancy rates per transfer were significantly higher in the D1-hCG. Significantly higher implantation and on-going pregnancy rates per embryo transfer were observed in D1-hCG (64%) compared to Control (41%).

Conclusions

Administration of D1-hCG prior to COH reduces rFSH use and enhances oocyte developmental competence to obtain top quality embryos, and improves implantation and on-going pregnancy rates. At present it is not clear if the benefit is related to producing an embryo that more likely to implant or a more receptive uterus, or merely fortuitous and related to the relatively small power of the study.

Keywords

Human choriogonadotropin Controlled ovarian hyperstimulation In vitro fertilization Oocyte developmental competence 

Notes

Acknowledgements

The authors would like to express appreciation to Claudia Vieira, Beto Jalegretti, Joyce Fioravanti, and Lia Rossi for technical and editorial input and comments. Additionally, the authors thank Dr. Carrie Cosola-Smith and Jeni Chapman for editorial comments.

References

  1. 1.
    Gourgeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17:121–55.Google Scholar
  2. 2.
    Mais V, Kazer RR, Cetel NS, Rivier J, Vale W, Yen SS. The dependency of folliculogenesis and corpus luteum function on pulsatile gonadotropin secretion in cycling women using a gonadotropin- releasing hormone antagonist as a probe. J Clin End Metab. 1986;62:1250–5.CrossRefGoogle Scholar
  3. 3.
    Ginther OJ, Beg MA, Gastal EL, Gastal MO, Baerwald AR, Pierson RA. Systemic concentrations of hormones during the development of follicular waves in mares and women: a comparative study. Reproduction. 2005;130:379–88. doi: 10.1530/rep. 1.00757.PubMedCrossRefGoogle Scholar
  4. 4.
    Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122:829–38. doi: 10.1530/rep.0.1220829.PubMedCrossRefGoogle Scholar
  5. 5.
    Albertini DF, Combelles CM, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction. 2001;121:647–53. doi: 10.1530/rep.0.1210647.PubMedCrossRefGoogle Scholar
  6. 6.
    Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci USA. 2002;99:2890–4. doi: 10.1073/pnas.052658699.PubMedCrossRefGoogle Scholar
  7. 7.
    Maruo T, Ladines-Llave CA, Samoto T, Matsuo H, Manalo A, Ito H, et al. Expression of Epidermal Growth Factor and Its Receptor in the Human Ovary during Follicular Growth and Regression. Endocrinology. 1993;132:924–31. doi: 10.1210/en.132.2.924.PubMedCrossRefGoogle Scholar
  8. 8.
    Webb R, Garnsworthy PC, Gong JG, Armstrong DG. Control of follicular growth: local interactions and nutritional influences. J Anim Sci. 2004;82(E. Suppl):E63–74.PubMedGoogle Scholar
  9. 9.
    Balasch J, Miro F, Burzaco I, Casamitjana R, Civico S, Ballesca JL, et al. The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone. Hum Reprod. 1995;10:1678–83.PubMedGoogle Scholar
  10. 10.
    Filicori M, Fazleabas AT, Huhtaniemi I, Licht P, Rao C, Tesarik J, et al. Novel concepts of human chorionic gonadotropin: reproductive system interactions and potential in the management of infertility. Fertil Steril. 2005;84:275–84. doi: 10.1016/j.fertnstert.2005.02.033.PubMedCrossRefGoogle Scholar
  11. 11.
    Törnell J, Bergh C, Selleskog U, Hillensjö T. Effect of recombinant human gonadotrophins on oocyte meiosis and steroidogenesis in isolated pre-ovulatory rat follicles. Mol Hum Reprod. 1995;1:219–22. doi: 10.1093/molehr/1.4.219.CrossRefGoogle Scholar
  12. 12.
    Burgués S. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001;16:2525–32. doi: 10.1093/humrep/16.12.2525.PubMedCrossRefGoogle Scholar
  13. 13.
    Greisen S, Ledet T, Ovesen P. Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells. Hum Reprod. 2001;16:2061–5. doi: 10.1093/humrep/16.10.2061.PubMedCrossRefGoogle Scholar
  14. 14.
    Thiruppathi P, Shatavi S, Dias JA, Radwanska E, Luborsky JL. Gonadotrophin receptor expression on human granulosa cells of low and normal responders to FSH. Mol Hum Reprod. 2001;7:697–704. doi: 10.1093/molehr/7.8.697.PubMedCrossRefGoogle Scholar
  15. 15.
    Schipper I, Hop WC, Fauser BC. The follicle-stimulating hormone (FSH) threshold/window concept examined by different interventions with exogenous FSH during the follicular phase of the normal menstrual cycle: duration, rather than magnitude, of FSH increase affects folli. J Clin Endocrinol Metab. 1998;83:1292–8. doi: 10.1210/jc.83.4.1292.PubMedCrossRefGoogle Scholar
  16. 16.
    Cédrin-Durnerin I, Grange-Dujardin D, Laffy A, Parneix I, Massin N, Galey J, et al. Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2004;19:1979–84. doi: 10.1093/humrep/deh369.PubMedCrossRefGoogle Scholar
  17. 17.
    De Placido G, Alviggi C, Perino A, Strina I, Lisi F, Fasolino A, et al. On behalf of the Italian collaborative group on: recombinant human luteinizing hormone recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial. Hum Reprod. 2005;20:390–6. doi: 10.1093/humrep/deh625.PubMedCrossRefGoogle Scholar
  18. 18.
    Andersen AN, Devroey P. Arce JC for the MERIT Group: Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006;21:3217–27. doi: 10.1093/humrep/del284.PubMedCrossRefGoogle Scholar
  19. 19.
    Tarlatzis B, Tavmergen E, Szamatowicz M, Barash A, Amit A, Levitas E, et al. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study. Hum Reprod. 2006;21:90–4. doi: 10.1093/humrep/dei293.PubMedCrossRefGoogle Scholar
  20. 20.
    Kolibianakis EM, Kalogeropoulou L, Griesinger G, Papanikolaou EG, Papadimas J, Bontis J, et al. Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis. Hum Reprod Update. 2007;13:445–52. doi: 10.1093/humupd/dmm008.PubMedCrossRefGoogle Scholar
  21. 21.
    Serafini P, Yadid I, Motta EL, Alegretti JR, Fioravanti J, Coslovsky M. Ovarian stimulation with daily late follicular phase administration of low-dose human chorionic gonadotropin for in vitro fertilization: a prospective, randomized trial. Fertil Steril. 2006;86:830–8. doi: 10.1016/j.fertnstert.2006.02.110.PubMedCrossRefGoogle Scholar
  22. 22.
    Filicori M, Cognigni GE, Samara A, Melappioni S, Perri T, Cantelli B, et al. The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction. Hum Reprod Update. 2002;8:543–57. doi: 10.1093/humupd/8.6.543.PubMedCrossRefGoogle Scholar
  23. 23.
    Filicori M, Cognigni GE, Gamberini E, Parmegiani L, Troilo E, Roset B. Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertil Steril. 2005;84:394–401. doi: 10.1016/j.fertnstert.2005.02.036.PubMedCrossRefGoogle Scholar
  24. 24.
    Hugues JN, Soussis J, Calderon I, Balasch J, Anderson RA, Romeu A. Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study. Hum Reprod. 2005;20:629–35. doi: 10.1093/humrep/deh682.PubMedCrossRefGoogle Scholar
  25. 25.
    Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340:17–8. doi: 10.1016/0140-6736(92)92425-F.PubMedCrossRefGoogle Scholar
  26. 26.
    Yadid I, Coslowsky M, Ribeiro CV, Motta ELA, Serafini PC. Follicle recruitment for IVF following administration of choriogonadotropin alpha (rec-hCG) on the day of spontaneous menstruation. Hum Reprod. 2005;20(Suppl. 1):i122–8.Google Scholar
  27. 27.
    Ji I, Lee C, Song Y, Conn M, Ji T. Cis- and Trans-activation of hormone receptors: the LH receptor. Mol Endocrinol. 2002;16:1299–308. doi: 10.1210/me.16.6.1299.PubMedCrossRefGoogle Scholar
  28. 28.
    Zelinski-Wooten MB, Hutchison JS, Trinchard-Lugan I, Hess DL, Wolf DP, Stouffer RL. Initiation of periovulatory events in gonadotrophin-stimulated macaques with varying doses of recombinant human chorionic gonadotrophin. Hum Reprod. 1997;12:1877–85. doi: 10.1093/humrep/12.9.1877.PubMedCrossRefGoogle Scholar
  29. 29.
    Young J, Rey R, Schaison G, Chanson P. Hypogonadotropic hypogonadism as a model of post-natal testicular anti-Mullerian hormone secretion in humans. Mol Cell Endocrinol. 2003;211:51–4. doi: 10.1016/j.mce.2003.09.020.PubMedCrossRefGoogle Scholar
  30. 30.
    Coomarasamy A, Afnan M, Cheema D, van der Veen F, Bossuyt PMM, van Wely M. Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long down-regulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis. Hum Reprod. 2008;23:310–5. doi: 10.1093/humrep/dem305.PubMedCrossRefGoogle Scholar
  31. 31.
    Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod. 2003;69:1023–31. doi: 10.1095/biolreprod.103.017772.PubMedCrossRefGoogle Scholar
  32. 32.
    Ginther OJ, Gastal EL, Gastal MO, Bergfelt DR, Baerwald AR, Pierson RA. Comparative study of the dynamics of follicular waves in mares and women. Biol Reprod. 2004;7:1195–201. doi: 10.1095/biolreprod.104.031054.CrossRefGoogle Scholar
  33. 33.
    Orvieto R, Meltzer S, Rabinson J, Zohav E, Anteby EY, Nahum R. GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of endometrial receptivity. Fertil Steril. 2008;90:1294–6. doi: 10.1016/j.fertnstert.2007.10.022.PubMedCrossRefGoogle Scholar
  34. 34.
    Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C. Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve. Fertil Steril. 2007;87:749–56. doi: 10.1016/j.fertnstert.2006.11.001.PubMedCrossRefGoogle Scholar
  35. 35.
    Louvet JP, Harman SM, Ross GT. Effects of human chorionic gonadotropin, human interstitial cell stimulating hormone and human follicle-stimulating hormone on ovarian weights in estrogen-primed hypophysectomized immature female rats. Endocrinology. 1975;96:1179–86.PubMedCrossRefGoogle Scholar
  36. 36.
    Filicori M, Flamigni C, Cognigni GE, Falbo A, Arnone R, Capelli M, et al. Different gonadotropin and leuprorelin ovulation induction regimens markedly affect follicular fluid hormone levels and folliculogenesis. Fertil Steril. 1996;65:387–93.PubMedGoogle Scholar
  37. 37.
    Mason HD, Cwyfan-Hughes SC, Heinrich G, Franks S, Holly JMP. Insulin-Like Growth Factor (IGF) I and II, IGF-Binding Proteins, and IGF-Binding Protein Proteases Are Produced by Theta and Stroma of Normal and Polycystic Human Ovaries. Clin Endocrinol Metab. 1996;81:276–84. doi: 10.1210/jc.81.1.276.CrossRefGoogle Scholar
  38. 38.
    Gómez E, de los Santos MJ, Ruiz A, Tarín JJ, Remohí J, Pellicer A. Effects of epidermal growth factor in the final stages of nuclear and cytoplasmic oocyte maturation in humans. Hum Reprod. 1993;8:691–4.PubMedGoogle Scholar
  39. 39.
    Artini PG, Battaglia C, D’ Ambrogio G, Barreca A, Droghini F, Volpe A, et al. Relationship between human oocyte maturity, fertilization and follicular fluid growth factors. Hum Reprod. 1994;9:902–6.PubMedGoogle Scholar
  40. 40.
    Kawamura K, Kawamura N, Mulders SM, Sollewijn G, Hsueh AJ. Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos. Proc Natl Acad Sci USA. 2005;102:9206–11. doi: 10.1073/pnas.0502442102.PubMedCrossRefGoogle Scholar
  41. 41.
    Paredes A, Romero C, Dissen GA, DeChiara TM, Reichardt L, Cornea A, et al. TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. Dev Biol. 2004;267:430–49. doi: 10.1016/j.ydbio.2003.12.001.PubMedCrossRefGoogle Scholar
  42. 42.
    Spears N, Molinek MD, Robinson LL, Fulton N, Cameron H, Shimoda K, et al. The role of neurotrophin receptors in female germ-cell survival in mouse and human. Development. 2003;130:5481–91. doi: 10.1242/dev.00707.PubMedCrossRefGoogle Scholar
  43. 43.
    Freidman S, Gurevich M, Shemesh M. Bovine cyclic endometrium contains high-affinity luteinizing hormone/human chorionic gonadotropin binding sites. Biol Reprod. 1995;52:1020–6. doi: 10.1095/biolreprod52.5.1020.PubMedCrossRefGoogle Scholar
  44. 44.
    Srisuparp S, Strakova Z, Brudney A, Mukherjee S, Reierstad S, Hunzicker-Dunn M, et al. Signal Transduction Pathways Activated by Chorionic Gonadotropin in the Primate Endometrial Epithelial Cells. Biol Reprod. 2003;68:457–64. doi: 10.1095/biolreprod.102.007625.PubMedCrossRefGoogle Scholar
  45. 45.
    Fields MJ, Shemesh M. Extragonadal Luteinizing Hormone Receptors in the Reproductive Tract of Domestic Animals. Biol Reprod. 2004;71:1412–8. doi: 10.1095/biolreprod.104.027201.PubMedCrossRefGoogle Scholar
  46. 46.
    Licht P, Fluhr H, Neuwinger J, Wallwiener D, Wildt L. Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol Cell Endocrinol. 2007;269:85–92. doi: 10.1016/j.mce.2006.09.016.PubMedCrossRefGoogle Scholar
  47. 47.
    Licht P, von Wolff M, Berkholz A, Wildt L. Evidence for cycle-dependent expression of full-length human chorionic gonadotropin/luteinizing hormone receptor mRNA in human endometrium and decidua. Fertil Steril. 2003;79(Suppl .1):718–23.PubMedCrossRefGoogle Scholar
  48. 48.
    Cameo P, Szmidt M, Strakova Z, Mavrogianis P, Sharpe-Timms KL, Fazleabas AT. Decidualization regulates the expression of the endometrial chorionic gonadotropin receptor in the primate. Biol Reprod. 2006;75:681–9. doi: 10.1095/biolreprod.106.051805.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Eduardo L. Motta
    • 1
    • 2
    • 4
  • Gary D. Smith
    • 5
    • 6
    • 7
    • 8
  • Paulo C. Serafini
    • 1
    • 2
    • 3
  • Marcio Coslovsky
    • 1
  • Pericles Hassun
    • 9
  • Andre M. Rocha
    • 1
    • 2
  • Isaac Yadid
    • 1
    Email author
  1. 1.Huntington Center for Reproductive Medicine of BrazilRio de JaneiroBrazil
  2. 2.Huntington Medicina Reprodutiva, Av. República do Líbano529-São PauloBrazil
  3. 3.Departamento de Ginecologia, Faculdade de MedicinaUniversidade de São Paulo255 São PauloBrazil
  4. 4.Departamento de GinecologiaUniversidade Federal de São Paulo740 São PauloBrazil
  5. 5.Department of Obstetrics and GynecologyUniversity of MichiganAnn ArborUSA
  6. 6.Department of UrologyUniversity of MichiganAnn ArborUSA
  7. 7.Department of PhysiologyUniversity of MichiganAnn ArborUSA
  8. 8.Reproductive Science ProgramUniversity of MichiganAnn ArborUSA
  9. 9.Genesis Genetics BrasilSão PauloBrazil

Personalised recommendations