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• W4249115758 abstract "We thank Dr. Chen and Dr. Wiwanitkit for their interest in our article (1Elassar 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. Published online April 25, 2011.Google Scholar). Dr. Chen’s comments in his letter are highly valid, and we agree that oral ovarian stimulation medications (including both clomiphene citrate and aromatase inhibitors) are associated with increased levels of luteinizing hormone (LH) that may contribute to premature luteinization. This theory was addressed in prior studies cited in our article (2Lee T.H. Lin Y.H. Seow K.M. Hwang J.L. Tzeng C.R. Yang Y.S. Effectiveness of cetrorelix for the prevention of premature luteinizing hormone surge during controlled ovarian stimulation using letrozole and gonadotropins: a randomized trial.Fertil Steril. 2008; 90: 113-120Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 3Verpoest W.M. 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: 166-172Abstract Full Text PDF PubMed Scopus (55) Google Scholar) where elevated LH levels were found in normally responding patients. Thus, the article he referred to (4Kucherov A. Polotsky A.J. Menke M. Isaac B. McAvey B. Buyuk E. et al.Aromatase inhibition causes increased amplitude, but not frequency of hypothalamic-pituitary output in normal women.Fertil Steril. 2011; 95: 2063-2066Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar) that reported the increase in LH pulse amplitude after letrozole administration was not the first. However, not all patients on letrozole experience a premature LH surge. In our study, we suggested other possible mechanisms, such as aged ovaries with diminished ovarian reserve being more prone to a premature LH surge, presumably due to reduced production of gonadotropin-releasing hormone (GnRH) attenuating factor (5de Ziegler D. Mattenberger C. Schwarz C. Ibecheole V. Fournet N. Bianchi-Demicheli F. New tools for optimizing endometrial receptivity in controlled ovarian hyperstimulation: aromatase inhibitors and LH/(mini)hCG.Ann NY Acad Sci. 2004; 1034: 262-277Crossref PubMed Scopus (8) Google Scholar). Irrespective of the mechanism, it is prudent to observe the patient’s serum LH levels more closely and to consider an early start of the antagonist administration even at lower estradiol (E2) levels. We also agree with Dr. Wiwanitkit that cost effectiveness may be one of the decisive factors when comparing two protocols that yield similar results. Patients on letrozole required fewer gonadotropins administered (1Elassar 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. Published online April 25, 2011.Google Scholar, 6Goswami S.K. 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: 2031-2035Crossref PubMed Scopus (146) Google Scholar). In our study, patients in the letrozole + gonadotropin protocol (LA) needed an average of 4,388 IU of gonadotropins versus 6,193 IU used by the luteal phase E2 and GnRH antagonist group (LPG), a difference of 1,805 IU that may add U.S. $2,496 to the medication expenses. Moreover, the LPG protocol adds the cost of the E2 patches as well as three extra ganirelix injections in the luteal phase before the start of ovarian stimulation. On the other hand, the LA group required 5 mg tablets of letrozole for 5 days. A comparative systematical analysis on cost shows that the letrozole protocol may result in a cost savings of U.S. $2,668 when compared with the LPG protocol. Thus, the aromatase inhibitor–based regimen may indeed be a potential preferred stimulation protocol based on cost effectiveness. Discussion on letrozole-Gn-antagonist group needing an early start of antagonistFertility and SterilityVol. 95Issue 8PreviewI read with great interest the article by Elassar et al. (1) in which they addressed the risk of a premature luteinizing hormone (LH) surge (LH ≥10 mIU/mL occurring before the detection of the leading follicle ≥18 mm in diameter) in the letrozole and gonadotropin-releasing hormone (GnRH) antagonist group and suggested that “an early start and possibly a higher dose of the antagonist should be considered when using letrozole.” This is a good concept, but they did not explore the cause. They mentioned “ovaries with diminished ovarian reserve are more prone to a premature LH surge.” However, it is not the cause leading to the high rate of premature LH surge associated with letrozole supplementation. Full-Text PDF Letrozole and gonadotropins versus luteal estradiol and GnRH-antagonist protocol: additional concernsFertility and SterilityVol. 95Issue 8PreviewIn their recent comparative study on letrozole and gonadotropins versus a luteal estradiol and gonadotropin-releasing hormone (GnRH) antagonist protocol, Elassar et al. (1) concluded that “aromatase inhibitor regimens can be a feasible alternative to the LPG protocol in recurrent low ovarian response.” Based on that study, the efficacy of both protocols seems similar. However, there are some differences, both in the agents and in the total dose of gonadotropins administered and the estradiol levels. Full-Text PDF" @default.
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• W4249115758 title "Reply of the Authors" @default.
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