Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols

Abstract

The efficacy of aromatase inhibitors incorporated in the ovarian stimulation protocols of poor-responder patients undergoing intracytoplasmic sperm injection-embryo transfer cycles was investigated. A total of 70 poor-responder patients were randomized into two groups on day 3 of their menstrual cycle. In Group A, an aromatase inhibitor (letrozole, 5 mg/day) was administered along with a fixed dosage (450 IU/day) of recombinant FSH (rFSH), whereas Group B were treated with the same rFSH dosage alone. A flexible regimen of gonadotrophin-releasing hormone antagonist was administered in both groups. The mean total dose of rFSH (2980 +/- 435 IU versus 3850 +/- 580 IU, P < 0.05) and serum concentrations of oestradiol on the day of human chorionic gonadotrophin administration (1870 +/- 159 pg/ml versus 2015 +/- 175 pg/ml, P < 0.05) were significantly lower in Group A compared with Group B, respectively. The rate of cycle cancellation due to poor ovarian response was lower in Group A (8.6%) than in Group B (28.6%), ( P < 0.05). The costs of achieving a clinical pregnancy were US$11560 and US$17584, and the clinical pregnancy rates per embryo transfer were 25.8% and 20%, in groups A and B, respectively. In conclusion, adjunctive letrozole administration seems to restore an IVF cycle by decreasing the rate of cycle cancellation and seems to reduce the cost by reducing the total gonadotrophin dosage.

Does the addition of clomiphene citrate or letrazole to gonadotropin treatment enhance the oocyte yield in poor responders undergoing IVF?

“…This was consistent with an earlier report that compared a high dose gonadotropin agonist protocol with low dose LZ with gonadotropin in a small number of poor responders and found cost saving effects with the use of LZ, but with no differences in cycle outcomes [7]. In another prospective trial, in direct comparison with antagonist gonadotropin cycles, the addition of LZ significantly reduced cycle cancellation rates due to poor responses and total gonadotropin utilization reduced overall costs [8]. A small meta-analysis however could not demonstrate the superiority of LZ addition over gonadotropins alone [19].…”

“…Although the prognosis for these women is guarded, leading some to consider other options such as egg donation or adoption, various adjunctive measures have been suggested to improve the ovarian response to gonadotropins. Since there is little evidence to support gonadotropin doses over 450-600 IU/day [1], current approaches have included the addition of oral agents such as clomiphene citrate [2,3] or letrazole [4][5][6][7][8][9], the administration of GnRH antagonists instead of agonists [10][11][12], microdose GnRH agonist "flare" [6,13] and other agents such as growth hormone (GH) [14] and most recently the suggestion that DHEA may be helpful [15].…”

“…To our knowledge no study has addressed the efficacy of the addition of CC to high dose gonadotropins in poor responders. Despite the relatively recent introduction of LZ in the repertoire of agents for ovulation induction [17], LZ has been used increasingly for different types of ovulation induction and has gained acceptance for use in poor responders [4][5][6][7][8][9]18]. A pilot study from 2005 showed that LZ supplemented antagonist cycles showed a significantly higher number of oocytes retrieved and increased implantation rates [5].…”

Editorial

“…Further trials used simultaneous regimen of letrozole and gonadotrophins in a GnRH antagonist protocol. 16,17,18 One observational study revealed a better implantation rate with a more favourable follicular fluid hormonal profile, 19 and one RCT confirmed the use of lower dosage of gonadotrophins and lower cancellation rate owing to poor response. 20 Recently improvements in IVF embryology with better fertilization rates and embryo quality mean that fewer oocytes are required by the laboratory.…”

Aromatase inhibitors in “poor” ovarian responders undergoing in vitro fertilization

“…Результаты такого применения этих препаратов в про-граммах ВРТ противоречивы [26, 49,[51][52][53]. В большинстве исследований было показано,…”