Short vs long agonist protocols in poor responders undergoing ivf

##plugins.themes.academic_pro.article.sidebar##

Published Feb 18, 2015
Download
pdf
Vol. 92 No. 10 (2014): Issue Oct 2014

##plugins.themes.academic_pro.article.main##

Kdous Moez
Elabed Meriem
Zhioua Fethi
Amel Zhioua

Abstract

Aim: Compare among poor responders: stimulation results, laboratory parameters and the final IVF results by assessing 2 different stimulation protocols: the long agonist protocol and the short agonist protocol.

Methods: An analytical retrospective study carried out over of period of 2 years: January 2006 and December 2007. During this period, a total of 1192 IVF cycles of ICSI type were performed in 892 patients. Inclusion criteria: short agonist or antagonist stimulated patients protocols and presenting two of the three following criteria: 1- Patients aged more than 38 years with an FSH plasmatic rate on the 3rd day of the cycle 9.5 UI/ml. 2- Antral follicle count (AFC) 5 for both ovaries. 3- Failure of anterior ovary stimulation: abandonment of cycle or ‹ 3 oocytes at data collection in a previous cycle. Exclusion criteria: PCOS or single ovary.

Results: 65 patients, undergoing 92 attempts of ICSI cycles have been included in this study. Long agonist protocol was performed in 48 cases and Short agonist protocol was performed in 44 cycles. Both groups were comparable as to age (40,09 ± 6, 59 vs 41, 04 ± 1,71 years; NS), BMI (25,2±3,92 vs 25,35±4,09 Kgm-2 ; NS), infertility type (primary 41% vs 59%;NS ; ou secondary 58% vs 40,9% ; NS), FSH (9,98±2,42 vs 10,01±2,75 ; NS) and antral follicle count on day 3 (4,13±1,12 vs 3,8±1,16 FA ; NS). The estradiol rate, dosed on the onset day was significantly higher in the short protocol group (1534,27±1034,34 vs 1133,31±1053,58 pg/ml; p=0.034). However, the consumed quantity of gonadotrophins was lower in the short protocol group (1550±235,45 vs 1725,55±450,35 UI, p=0.01). A total of 13 cycles was stopped: 9 times for the long protocol (18.75 %) and 4 times for the short protocol (9.09 %) with statistically significant difference. The number of collected oocytes was significantly higher in the short protocol (7,64±3,70 vs 4,55±2,01, P<0.001). We significantly obtained more embryos in the short protocol (4,31±2,9 vs 2,16±2,2 embryos ; p<0,001). With higher number of grade 1 embryos (2,61 vs 1,14 embryons; p<0.001).The results in terms of pregnancy and living births show no significant difference between the 2 groups.

Conclusion: The short protocol is more suited to the profile of ovarian poor responders. The long protocol standard has no place in poor responders. However, the long micro dose protocol and the long degressed micro dose protocol yield results at least equivalent to the short protocol.

Keywords:

IVF, ICSI, Poor responders, short agonist, long agonist.

##plugins.themes.academic_pro.article.details##

References

  1. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; on behalf of the ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011;26 :1616-1624.
  2. Hazout A, Bouchard P, Seifer DB, Aussage P, Junca AM, Cohen-Bacrie P. Serum antimüllerian hormone/müllerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B, or estradiol. Fertil Steril 2004;82:1323-9
  3. Peñarrubia J, Balasch J, Fábregues F, Carmona F, Casamitjana R, Moreno V, Calafell JM, Vanrell JA. Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment. Hum Reprod 2000;15:1499-504
  4. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome .The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Fertil Steril 2004;81:19-25
  5. Detti L, Williams DB, Robins JC, Maxwell RA, Thomas MA. A comparison of three downregulation approaches for poor responders undergoing in vitro fertilization. Fertil Steril 2005;84:1401-1415.
  6. Weissman A. Farhi J. Roybitrt M.Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embiyo transfer. Fertil Steril 2003; 79:886-892
  7. Ta demir M, Ta demir I, Kodama H, Fukuda J, Tanaka T. Short protocol of gonadotropin releasing hormone agonist administration gave better results in long protocol poor-responders in IVF-ET. J Obstet Gynecol 1996;22:73-7.
  8. Yakin K, Kahraman S, Vanlioglu F, Kumtepe Y, Findikli N. Comparison of microdose and standard doses of GnRH analogue in flare protocols for controlled ovarian hyperstimulation in poor responders. Fertil Steril 2000;76:337.
  9. Merviel P, Lourdel E, Boulard V, Cabry R, Claeys C, Oliéric MF, Sanguinet P, Brasseur F, Henri I, Copin H. Premature ovarian failure: which protocols?. Gynecol Obstet Fertil 2008;36:872-81.
  10. Surrey E, Bower J, Hill D, Ramsey J, Surrey M. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril 1998; 69:419 -24
  11. Reshef E, Lei Z.M, Rao ChV, Pridham D.D, Chegini N, Luborsky J.L. The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua. J Clin Endocrinol Metab 1990;70:421-30.
  12. Scott RT, Navot D. Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization. Fertil Steril 1994;61:880-5.
  13. Barri PN, Coroleu B, Martinez F, Veiga A. Stimulation protocols for poor responders and aged women. Mol Cell Endocrinol 2000; 166:15-20.
  14. Cummins J, Yovich J, EdirisingheW, Yovich J. Pituitary down-regulation using leuprolide for the intensive ovulation management of poor prognosis patients having in vitro fertilization treatments. J In Vitro Fert Embryo Transf 1989;6:345-52.
  15. McKenna K, Foster P, McBain J, Martin M, Johnston W. Combined treatment with gonadotropin-releasing hormone agonist and gonadotropins in poor responders to hyperstimulation for in vitro fertilization (IVF): clinical and endocrine results. Aus NZJ Obstet Gynecol 1989;29:428-32.
  16. Feldberg D, Farhi J, Ashkenazi J, Dicker D, Shalev J, Ben Rafael Z. Minidose gonadotropin releasing hormone agonist is the treatment of choice in poor responders with high follicle-stimulating hormone levels. Fertil Steril 1994; 62:343- 6.
  17. . Ben-Rafael Z, Benadiva CA, Ausmanas M, Barber B, Blasco L, FlickingerGL, et al. Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program. Fertil Steril 1987;48: 964-8.
  18. Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol. Fertil Steril 1997;67:93-7.
  19. Biljan M, Mahutte N, Dean N, Hemmings R, Bissonnette F, Tan S. Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent pregnancy rates. Fertil Steril 1998;70:1063-9.
  20. Lindheim S, Barad D, Witt B, Ditkoff E, Sauer M. Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation. J Assist Reprod Genet 1996;16:745-7.
  21. Al-Mizyen E, Sabatini L, Lower AM, Wilson CMY, Al-Shawaf T Grudzinskas JG. Does pretreatment with progestogen or oral contraceptive pills in low responders followed by the GnRHa flare protocol improve the outcome of IVF-ET? J Assist Reprod Genet 2000;17:140-6
  22. Leondires MP, Escalpes M, Segars JH, Scott RT, Miller BT. Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization. Fertil Steril 1999;72:1018-23.
  23. . Olivennes F, Fanchin R, De Ziegler D, Frydman R. Poor responders: screening and treatment possibilities. J Assist Reprod Genet 1993;10:115-7.
  24. Tavmergen E, Göker EN, Sendag F, Sendag H, Levi R. Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy. Arch Gynecol Obstet 2002;266:5-11.
  25. Loutradis D, Stefanidis K, Drakakis P, et al. Comparison between ‘‘short'' and ‘‘long'' protocols in an ICSI programme. European Journal of Obstetrics & Gynecol Reprod Biol 2005;120:69-72.
  26. Hillier S.G. Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod 1994;9:188-91.
  27. Valbuena D, Martin J, De Pablo JL. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril 2001;76:962-8.