open access
Letrozole as an adjunct treatment in antagonist cycles that previously failed in poor responders
, 1, 1, 1, 1
Affiliations- University of Health Sciences Tepecik Education and Research Hospital, Izmir, Turkey
open access
Abstract
Objectives: To investigate whether adding letrozole in the early follicular phase of a gonadotropin-releasing hormone (GnRH) antagonist (GA) stimulation cycle improves in vitro fertilization (IVF) outcomes in poor responder patients.
Material and methods: To be included in this study, patients had to have had at least one previous GA cycle and a subsequent GA cycle with added early follicular phase letrozole (LzGA). A total of 41 poor responder patients were identified based on the Bologna criteria.
Results: The LzGA group had a lower dosage of follicular stimulating hormone (FSH) (p = 0.001), the duration of stimulation days (p = 0.015) and the duration of GnRH antagonist stimulation days (p = 0.033) when compared with controls. Comprehensive analysis of the cycle characteristics showed that the number of oocytes retrieved, the number of MII oocytes retrieved, the number of fertilized oocytes, and the fertilization rate were significantly higher in the LzGA cycle (p = 0.041, p = 0.019, p = 0.008, p = 0.01, respectively). The rate of cycle cancellation was lower in the LzGA group (24.4%) than in the GA group (48.8%), (p < 0.001). Although LzGA administration demonstrated a trend toward improved implantation and clinical pregnancy rates, this was an insignificant trend (p = 1.000, p = 0.177, respectively).
Conclusions: Adjunctive letrozole administration seems to restore an IVF cycle by improving the cycle characteristics and reducing the total gonadotrophin dosage.
Abstract
Objectives: To investigate whether adding letrozole in the early follicular phase of a gonadotropin-releasing hormone (GnRH) antagonist (GA) stimulation cycle improves in vitro fertilization (IVF) outcomes in poor responder patients.
Material and methods: To be included in this study, patients had to have had at least one previous GA cycle and a subsequent GA cycle with added early follicular phase letrozole (LzGA). A total of 41 poor responder patients were identified based on the Bologna criteria.
Results: The LzGA group had a lower dosage of follicular stimulating hormone (FSH) (p = 0.001), the duration of stimulation days (p = 0.015) and the duration of GnRH antagonist stimulation days (p = 0.033) when compared with controls. Comprehensive analysis of the cycle characteristics showed that the number of oocytes retrieved, the number of MII oocytes retrieved, the number of fertilized oocytes, and the fertilization rate were significantly higher in the LzGA cycle (p = 0.041, p = 0.019, p = 0.008, p = 0.01, respectively). The rate of cycle cancellation was lower in the LzGA group (24.4%) than in the GA group (48.8%), (p < 0.001). Although LzGA administration demonstrated a trend toward improved implantation and clinical pregnancy rates, this was an insignificant trend (p = 1.000, p = 0.177, respectively).
Conclusions: Adjunctive letrozole administration seems to restore an IVF cycle by improving the cycle characteristics and reducing the total gonadotrophin dosage.
Keywords
letrozole; ovarian stimulation; poor response; diminished ovarian reserve; antagonist cycle
About this articleTitle
Letrozole as an adjunct treatment in antagonist cycles that previously failed in poor responders
Journal
Issue
Article type
Research paper
Pages
267-272
Published online
2021-06-24
Page views
5364
Article views/downloads
1438
DOI
Pubmed
Bibliographic record
Ginekol Pol 2022;93(4):267-272.
Keywords
letrozole
ovarian stimulation
poor response
diminished ovarian reserve
antagonist cycle
Authors
Melek Turaç Kaçar
Alper Biler
Can Köse
Ebru Şahin Güleç
Ahmet Demir
References (31)- Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015; 103(3): e9–ee17.
- Toner J, Philput C, Jones G, et al. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age**Presented as the Prize Paper for the Society of Assisted Reproductive Technologies at the Annual Meeting of The American Fertility Society, Washington, D.C., October 15 to 18, 1990. Fertility and Sterility. 1991; 55(4): 784–791.
- Wardle PG, Mclaughlin EA, Mcdermott A, et al. ENDOMETRIOSIS AND OVULATORY DISORDER: REDUCED FERTILISATION IN VITRO COMPARED WITH TUBAL AND UNEXPLAINED INFERTILITY. The Lancet. 1985; 326(8449): 236–239.
- Fasouliotis SJ, Simon A, Laufer N. Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet. J Assist Reprod Genet. 2000; 17(7): 357–373.
- Mahutte NG, Arici A. Poor responders: does the protocol make a difference? Curr Opin Obstet Gynecol. 2002; 14(3): 275–281.
- Surrey E, Schoolcraft W. Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques. Fertility and Sterility. 2000; 73(4): 667–676.
- Tarlatzis BC, Zepiridis L, Grimbizis G, et al. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update. 2003; 9(1): 61–76.
- Ubaldi FM, Rienzi L, Ferrero S, et al. Management of poor ovarian responders in IVF. Reproductive BioMedicine Online. 2005; 10(2): 235–246.
- Pandian Z, McTavish AR, Aucott L, et al. Interventions for 'poor responders' to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010(1): CD004379.
- Akhtar M, Njar V, Wright JN. Mechanistic studies on aromatase and related CC bond cleaving P-450 enzymes. The Journal of Steroid Biochemistry and Molecular Biology. 1993; 44(4-6): 375–387.
- Mitwally MFM, 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.
- Mitwally M, Casper R. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertility and Sterility. 2001; 75(2): 305–309.
- Mitwally M, Casper R. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders1 1Recipient of the 2001 Pacific Coast Reproductive Society-Wyeth-Ayerst Award. Fertility and Sterility. 2002; 77(4): 776–780.
- Mitwally MFM, Casper RF. Aromatase inhibitors for the treatment of infertility. Expert Opin Investig Drugs. 2003; 12(3): 353–371.
- Healey S, Tan SL, Tulandi T, et al. Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril. 2003; 80(6): 1325–1329.
- Davar R, Oskouian H, Ahmadi S, et al. GnRH Antagonist/Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing In Vitro Fertilization. Taiwanese Journal of Obstetrics and Gynecology. 2010; 49(3): 297–301.
- 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.
- 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.
- Schoolcraft WB, Surrey ES, Minjarez DA, et al. Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol? Fertil Steril. 2008; 89(1): 151–156.
- Yarali H, Esinler I, Polat M, et al. Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol. Fertil Steril. 2009; 92(1): 231–235.
- Ozmen B, Sönmezer M, Atabekoglu CS, et al. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online. 2009; 19(4): 478–485.
- Ferraretti AP, La Marca A, Fauser BC, et al. 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(7): 1616–1624.
- Hardarson T, Hanson C, Sjögren A, et al. Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. Hum Reprod. 2001; 16(2): 313–318.
- 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): 1270–1283.
- Lee VC, Chan CC, Ng EH, et al. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial. Reprod Biomed Online. 2011; 23(3): 380–388.
- Lee KH, Kim CH, Suk HJ, et al. The effect of aromatase inhibitor letrozole incorporated in gonadotrophin-releasing hormone antagonist multiple dose protocol in poor responders undergoing in vitro fertilization. Obstet Gynecol Sci. 2014; 57(3): 216–222.
- Ebrahimi M, Akbari-Asbagh F, Ghalandar-Attar M, et al. Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT. Int J Reprod Biomed. 2017; 15(2): 101–108.
- Sunkara SK, Rittenberg V, Raine-Fenning N, et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011; 26(7): 1768–1774.
- Samara N, Reis D, Danielli Miller N, et al. What are the best predictors for successful GnRH antagonist protocol in in vitro fertilization (IVF) treatment? Gynecol Endocrinol. 2015; 31(11): 877–879.
- Moini A, Lavasani Z, Kashani L, et al. 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): 653–660.
- Klinkert ER, Broekmans FJM, Looman CWN, et al. 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(5): 1247–1253.
