Gonadotropin Versus Gonadotropin/Letrozole Protocol in Previously Failed Antagonist Cycles in Patients with Low Prognosis

Year 2023, , 192 - 198, 20.10.2023

Can Kose , Ahmet Demir , Kübra Karakolcu , Ebru Şahin Güleç

https://doi.org/10.56766/ntms.1347840

Abstract

Objective: Letrozole is an aromatase inhibitor which has been used for ovulation induction. Our aim is to evaluate the effectiveness of adding letrozole to gonadotropins in the early follicular phase of gonadotropin-releasing hormone antagonist (GnRH-a) protocol in patients with poor ovarian response who had failed in the preceding GnRH-a cycle.
Materials and Method: Ninety-eight patients with poor ovarian response who had previously failed GnRH-a cycle were included. Patients (n; 58) who were treated with letrozole plus gonadotropins (LzGA) were compared with patients (n; 40) who received gonadotropins (GT). The number of total oocytes retrieved, the number of MII oocytes and fertilized oocytes, fertilization and implantation ratios, the rate of cycle cancellation as well as clinical pregnancy and live birth rates
Results: The LzGA group had a significantly shorter duration of GnRH-a stimulation and higher progesterone level at trigger day (p=0.005, p=0.049 respectively). Although letrozole administration demonstrated lower estradiol levels at trigger day and the total dose of gonadotropins used were lower in LzGA group, this was statistically non-significant (p=0.13, p=0.13 respectively).
Conclusion: Adding letrozole to gonadotropins in GnRH-a protocol in patients with poor prognosis did not improve pregnancy outcomes. But it seems to decrease IVF costs by reducing the GnRH-antagonist and gonadotropin dosage.

Keywords

Letrozole, Gonadotropin, Poor Ovarian Reserve, IVF

Supporting Institution

None

Project Number

None

Thanks

We would like to thank Research Assistant Çevik Gürel for his contribution in the editing of the article.

References

• 1. Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of 'Low prognosis patients in Assisted Reproductive Technology' and its proposed marker of successful outcome. F1000Res. 2016; 5:2911. 2. Haas J, Casper RF. In vitro fertilization treatments with the use of clomiphene citrate or letrozole. Fertil Steril. 2017; 108(4):568-71. 3. Kamath MS, Maheshwari A, Bhattacharya S, Lor KY, Gibreel A. Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation. Cochrane Database Syst Rev. 2017; 11(11):CD008528.
• 4. Mitwally MF, Casper RF, Diamond MP. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment. Reprod Biol Endocrinol. 2005; 3:54.
• 5. Shapiro DB, Mitchell-Leef D. GnRH antagonist in in vitro fertilization: where we are now. Minerva Ginecol. 2003; 55(5):373-88.
• 6. Garcia-Velasco JA, Moreno L, Pacheco 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(1):82-87.
• 7. Goswami SK, Das T, Chattopadhyay R, 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(9):2031-2035.
• 8. Ozmen B, Sönmezer M, Atabekoglu CS, Olmus H. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online. 2009; 19(4):478-85.
• 9. Schoolcraft WB, Surrey ES, Minjarez DA, Stevens JM, Gardner DK. Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol?. Fertil Steril. 2008; 89(1):151-56.
• 10. Verpoest WM, Kolibianakis E, Papanikolaou E, Smitz J, Van Steirteghem A, Devroey P. Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study. Reprod Biomed Online. 2006; 13(2):166-72.
• 11. Sakkas, Denny, and David K. Gardner. Evaluation of embryo quality. Textbook of assisted reproductive techniques, laboratory and clinical perspectives. Martin Dunitz Ltd, London, UK, 2001. 228-29.
• 12. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011; 26(6):1270-83.
• 13. Amsterdam A, Hanoch T, Dantes A, Tajima K, Strauss JF, Seger R. Mechanisms of gonadotropin desensitization. Mol Cell Endocrinol. 2002; 187(1-2):69-74.
• 14. Bastu E, Buyru F, Ozsurmeli M, Demiral I, Dogan M, Yeh J. A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response. Eur J Obstet Gynecol Reprod Biol. 2016; 203:30-34.
• 15. Moini A, Lavasani Z, Kashani L, Mojtahedi MF, Yamini N. Letrozole as co-treatment agent in ovarian stimulation antagonist protocol in poor responders: A double-blind randomized clinical trial. Int J Reprod Biomed. 2019; 17(9):653-60.
• 16. Lee VC, Chan CC, Ng EH, Yeung WS, Ho PC. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial. Reprod Biomed Online. 2011; 23(3):380-88.
• 17. Yucel O, Ekin M, Cengiz H, Zebitay AG, Yalcinkaya S, Karahuseyinoglu S. Comparison of estradiol and progesterone priming/antagonist/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection. Gynecol Endocrinol. 2014; 30(9):653-56.