Letrozole and gonadotropins versus luteal estradiol and gonadotropin-releasing hormone antagonist protocol in women with a prior low response to ovarian stimulation

Elassar, A.A.; Engmann, Lawrence; Nulsen, John; Benadiva, Claudio

doi:10.1016/j.fertnstert.2011.03.103

Cited by 18 publications

(14 citation statements)

References 47 publications

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“…Clinical outcomes were comparable in both groups (12). These results were in accordance with what has been reported by various studies (19, 31-33). …”

Section: Discussionsupporting

confidence: 94%

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

Ebrahimi

Akbari-Asbagh

Ghalandar-Attar

2017

IJRM

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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.

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“…Clinical outcomes were comparable in both groups (12). These results were in accordance with what has been reported by various studies (19, 31-33). …”

Section: Discussionsupporting

confidence: 94%

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

Ebrahimi

Akbari-Asbagh

Ghalandar-Attar

2017

IJRM

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“…Patients on letrozole required fewer gonadotropins administered (1,6). In our study, patients in the letrozole þ gonadotropin protocol (LA) needed an average of 4,388 IU of gonadotropins versus 6,193 IU used by the luteal phase E 2 and GnRH antagonist group (LPG), a difference of 1,805 IU that may add U.S. $2,496 to the medication expenses.…”

mentioning

confidence: 81%

“…We thank Dr. Chen and Dr. Wiwanitkit for their interest in our article (1). 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.…”

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confidence: 89%

Reply of the Authors

Elassar

Benadiva

2011

Fertility and Sterility

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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 (2, 3) where elevated LH levels were found in normally responding patients. Thus, the article he referred to (4) 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 (5). 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 (E 2 ) 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 (1, 6). In our study, patients in the letrozole þ gonadotropin protocol (LA) needed an average of 4,388 IU of gonadotropins versus 6,193 IU used by the luteal phase E 2 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 E 2 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.

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“…In 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.…”

mentioning

confidence: 99%

Letrozole and gonadotropins versus luteal estradiol and GnRH-antagonist protocol: additional concerns

Wiwanitkit

2011

Fertility and Sterility

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Letrozole and gonadotropins versus luteal estradiol and gonadotropin-releasing hormone antagonist protocol in women with a prior low response to ovarian stimulation

Cited by 18 publications

References 47 publications

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

Reply of the Authors

Letrozole and gonadotropins versus luteal estradiol and GnRH-antagonist protocol: additional concerns

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