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Volume 15, Issue 2 (3-2017)
IJRM 2017, 15(2): 101-108 |
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Ebrahimi M, Akbari-Asbagh F, Ghalandar-Attar M. Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT. IJRM 2017; 15 (2) :101-108
URL: http://ijrm.ir/article-1-798-en.html
URL: http://ijrm.ir/article-1-798-en.html
1- Department of Obstetrics and Gynecology, IVF Unit, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran. , Maeb214@yahoo.com; maebrahimi@tums.ac.ir
2- Department of Obstetrics and Gynecology, IVF Unit, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
3- Department of Obstetrics and Gynecology, IVF Unit, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran.
2- Department of Obstetrics and Gynecology, IVF Unit, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
3- Department of Obstetrics and Gynecology, IVF Unit, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abstract: (3776 Views)
Background:Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies.
Objective: The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection.
Materials and Methods: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate.
Results: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12).
Conclusion: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.
Objective: The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection.
Materials and Methods: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate.
Results: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12).
Conclusion: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.
Type of Study: Original Article |
References
1. Oudendijk JF, Yarde F, Eijkemans MJC, Broekmans FJM, Broer SL. The poor responder in IVF: is the prognosis always poor? A systematic review. Hum Reprod 2012; 18: 1-11. [DOI:10.1093/humupd/dmr037]
2. Shastri SM, Barbieri E, Kligman I, Schoyer KD, Davis OK, Rosenwaks Z. Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide. Fertil Steril 2011; 95: 592-595. [DOI:10.1016/j.fertnstert.2010.10.003]
3. Zarek SM, Muasher SJ. Mild/minimal stimulation for in vitro fertilization: an old idea that needs to be revisited. Fertil Steril 2011; 95: 2449-2455. [DOI:10.1016/j.fertnstert.2011.04.041]
4. Mutlu MF, Erdem M, Erdem A , Yildiz S, Multu I, Arisoy O, et al. Antral follicle count determines poor ovarian response better than anti-müllerian hormone but age is the only predictor for live birth in in vitro fertilization cycles. J Assist Reprod Genet 2013; 30: 657-685. [DOI:10.1007/s10815-013-9975-3]
5. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of "poor response" to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011; 26: 1616-1624. [DOI:10.1093/humrep/der092]
6. Polyzos NP, Devroey P. "A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel?" Fertil Steril 2011; 96: 1058-1061. [DOI:10.1016/j.fertnstert.2011.09.048]
7. Ubaldi FM, Rienzi L, Ferrero S. Management of poor responders in IVF. Reprod BioMed Online 2005; 10: 235-246. [DOI:10.1016/S1472-6483(10)60946-7]
8. Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol 2011; 9: 67. [DOI:10.1186/1477-7827-9-67]
9. Kolibianakis E, Albano C, Zikopoulos K, Kahn JA, Van Steirteghem A, Devroey P. GnRH antagonists in poor responders. Acta Obstet Gynecol Scand 2004; 83: 1216-1217. [DOI:10.1111/j.0001-6349.2004.00480.x]
10. Xiao J, Chang Sh, Chen Sh. The effectiveness of gonadotropin-releasing hormone antagonist in poor ovarian responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril 2013; 100: 1594-1601. [DOI:10.1016/j.fertnstert.2013.08.024]
11. Yarali H, Esinler I, Polat M, Bozdag G, Tiras B. Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol. Fertil Steril 2009; 92: 231-235. [DOI:10.1016/j.fertnstert.2008.04.057]
12. Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, et al. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod 2004; 19: 2031-2035. [DOI:10.1093/humrep/deh359]
13. Mitwally M, Casper R. Aromatase inhibition improves ovarian response to follicle stimulation hormone in poor responders. Fertil Steril 2002; 77: 776-780. [DOI:10.1016/S0015-0282(01)03280-0]
14. Akhtar M, Njar V, Wright JN. Mechanistic studies on aromatase and related C-C bond elevating P-450 enzymes. J Steroid Biochem Mol Biol 1993; 44: 375-387. [DOI:10.1016/0960-0760(93)90241-N]
15. Mitwally M, Casper RF, Diamond MP. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment. Reprod Biol Endocriol 2005; 3:54. [DOI:10.1186/1477-7827-3-54]
16. Casper RF, Mitwally MFM. Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clin Obstet Gynecol 2011; 54: 685-695. [DOI:10.1097/GRF.0b013e3182353d0f]
17. Verpoest WM, Kolibianakis E, Papanikolaou E, Smitz J, Van Steirteghem A, Devroev P. Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study. Reprod Biomed Online 2006; 13: 166-172. [DOI:10.1016/S1472-6483(10)60611-6]
18. Fasouliotis SJ , Laufer N, Sabbagh-Ehrlich Sh, Lewin A, Hurwitz A, Simon A. Gonadotropin-Releasing Hormone (GnRH)-Antagonist Versus GnRH-Agonist in Ovarian Stimulation of Poor Responders Undergoing IVF. J Assist Reprod Genet 2003; 20: 455-460. [DOI:10.1023/B:JARG.0000006707.88826.e7]
19. Garcia-Velasco JA, Moreno L, Pacheco A, Guillen A, Duque L, Requena A, et al . The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril 2005; 84: 82-87. [DOI:10.1016/j.fertnstert.2005.01.117]
20. Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Møllgard K, Wreford Andersen E, et al. In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Mol Hum Reprod 2011; 17: 63-70. [DOI:10.1093/molehr/gaq073]
21. Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D . Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum Reprod 2003; 18: 598-603. [DOI:10.1093/humrep/deg115]
22. Demeestere I, Gervy C, Centner J, Devreker F, Englert Y, Delbaere A. Effect of insulin –like growth factor-I during preantral follicular culture on steroidogenesis, in vitro oocyte maturation , and embryo development in mice. Biol Reprod 2004; 70: 1664-1669. [DOI:10.1095/biolreprod.103.023317]
23. Frattarelli JL, Peterson EH. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril 2004; 81: 1713-1714. [DOI:10.1016/j.fertnstert.2003.11.032]
24. Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006; 21: 2845-2849. [DOI:10.1093/humrep/del254]
25. Sioufi A, Sandrenan N, Godbillon J, Trunet P, Czendlik C, Howald H, et al. Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration. Biopharm Drug Dispos 1997; 18: 489-497.
https://doi.org/10.1002/(SICI)1099-081X(199708)18:6<489::AID-BDD36>3.0.CO;2-P [DOI:10.1002/(SICI)1099-081X(199708)18:63.0.CO;2-P]
26. Biljan MM, Hemmings R, Brassard N. The Outcome of 150 Babies Following the Treatment with Letrozole or Letrozole and Gonadotropins. Fertil Steril 2005; 84: S95. [DOI:10.1016/j.fertnstert.2005.07.230]
27. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril 2006; 85: 1761-1765. [DOI:10.1016/j.fertnstert.2006.03.014]
28. Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005; 192: 381-386. [DOI:10.1016/j.ajog.2004.08.013]
29. Papanikolaou EG, Bourgain C, Kolibianakis E. Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in absence of secretory changes. Hum Reprod 2005; 20: 1541-1547. [DOI:10.1093/humrep/deh793]
30. Sekhon L, Lee JA, Whitehouse M, Copperman AB, Grunfeld L. Letrozole as an adjunct in GnRH antagonist cycles improves IVF outcomes in poor responders. Fertil Steril 2014; 102: e 221.
31. Elassar A, Engmann L, Nulsen J, Benadiva C. Letrozole and gonadotropins versus luteal estradiol and gonadotropin-releasing hormone antagonist protocol in women with a prior low response to ovarian stimulation. Fertil Steril 2011; 95: 2330-2334. [DOI:10.1016/j.fertnstert.2011.03.103]
32. Kapoor M, Hurwitz JM, Polotsky AJ, Richlin SS, Chi L, Leondires MP. Letrozole in combination with gonadotropins decreases cancellation rates and improves ongoing pregnancy rates per transfer in poor responders. Fertil Steril 2007; 88: S100. [DOI:10.1016/j.fertnstert.2007.07.325]
33. Rodrigues RS, Setti AS b, Braga DPAF, Iaconelli A, Borges E. Letrozole in poor responders: association of practical, saving and good results. Fertil Steril 2012; 98: S78. [DOI:10.1016/j.fertnstert.2012.07.282]
34. Al-Fadhli R, Silvestre C, Buckett W, Tan SL, Tulandi T. A randomized trial of superovulation with two different doses of letrozole. Fertil Steril 2006; 85: 161-164. [DOI:10.1016/j.fertnstert.2005.07.1283]
35. Mitwally MF, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003; 18: 1588-1597. [DOI:10.1093/humrep/deg311]
36. Badawy A, Mitwally M, Fawzy M. Randomized controlled trial of three doses of letrozole for ovulation induction in patients with unexplained infertility. Reprod Biomed 2007; 14: 559-562. [DOI:10.1016/S1472-6483(10)61046-2]
37. Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005; 192: 381-386. [DOI:10.1016/j.ajog.2004.08.013]
38. Veleva Z, Jarvela IY, Nuojua-Huttunen S, Martikainen H, Tapanainen JS. An initial low response predicts poor outcome in in vitro fertilization/intracytoplasmic sperm injection despite improved ovarian response in consecutive cycles. Fertil Steril 2005; 83: 1384-1390. [DOI:10.1016/j.fertnstert.2004.11.056]
39. Klinkert ER, Broekmans FJM, Looman CWN, TeVelde ER. A poor response in the first in vitro fertilization cycle is not necessarily related to a poor prognosis in subsequent cycles. Fertil Steril 2004; 81: 1247-1253. [DOI:10.1016/j.fertnstert.2003.10.030]
40. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000; 15: 2129-2132. [DOI:10.1093/humrep/15.10.2129]
41. Massin N, Cedrin-Durnerin I, Coussieu C, Galey-Fintaine J, Wolf JP, Hugues JN. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique-a prospective, randomized, double blind study. Hum Reprod 2006; 21: 1204-1211. [DOI:10.1093/humrep/dei481]
42. Geraedts J, Sermon K. Preimplantation genetic study 2.0: the theory. Mol Hum Reprod 2016; 22: 839-844. [DOI:10.1093/molehr/gaw033]
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