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

https://doi.org/10.1016/j.rbmo.2009.05.007Get rights and content

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.

Introduction

Poor ovarian response to standard ovulation induction protocols, which mainly reflects diminished ovarian reserve, still remains as a major challenge in assisted reproduction. The clinical outcomes of assisted reproduction were reported as negatively affected in cases with poor ovarian response; however, the definition of poor response is still controversial (Kailasam, Muasher). Increased cycle cancellation and increased gonadotrophin consumption are the main encountered problems in ovulation induction regimens of these patients. Therefore, in addition to low success and decreased conception rates, the cost of treatment also increases.

Gonadotrophin-releasing hormone (GnRH) antagonists, due to their reported advantages over GnRH agonists, have more recently been recommended in ovarian stimulation cycles of poor-responders (Fasouliotis, Shapiro and Mitchell-Leef, 2003, D’Amato). Aromatase inhibitors (AI), other recent ovulation induction agents, suppress serum oestradiol concentrations, which results in a subsequent marked increase in serum FSH and LH concentrations. Letrozole, an AI, was reported to be an effective agent both in ovulation induction and in ovarian stimulation without any negative effects on the endometrium (Mitwally and Casper, 2001, Mitwally and Casper, 2002, Mitwally and Casper, 2003, Fisher, Mitwally). Furthermore, treatment with AI together with recombinant FSH (rFSH) in IVF cycles of poor-responders was found to be effective in reducing gonadotrophin consumption and consequently the cost of IVF compared with rFSH-only regimens in GnRH analogue down-regulated cycles (Goswami et al., 2004). In consequence, this study aimed to investigate the efficacy of AI in poor-responders undergoing ovarian stimulation with an GnRH antagonist regimen.

Section snippets

Subjects

A total of 70 infertile women who were planned to undergo their second intracytoplasmic sperm injection (ICSI) – embryo transfer cycle and with a history of poor ovarian response in their first ICSI – embryo transfer cycle were enrolled in the study. Written informed consent was taken from all subjects before initiation of the treatment cycle. All of these enrolled patients had their first ICSI – embryo transfer cycle or the ovarian stimulation scheme at least 6 months prior to the current

Results

Details of infertility aetiologies in each group are given in Table 2. The mean age of participants and the mean basal hormone concentrations were not different among the groups. The mean number of follicles >14 mm or >17 mm on the day of HCG administration, mean number of retrieved oocytes and mean number of mature oocytes were similar in both groups (Table 3). In total, 145 and 107 MII oocytes were retrieved in groups A and B, respectively. However, the mean concentration of serum oestradiol on

Discussion

Aromatase inhibitors have been introduced as an alternative ovulation induction agent either alone (Mitwally and Casper, 2001) or as an adjunctive ovulation induction agent along with gonadotrophins in ovarian stimulation (Mitwally and Casper, 2003). It was reported that transient inhibition of aromatase activity in early follicular phase (on days 5–9) with letrozole results in ovarian stimulation similar to clomiphene citrate with no apparent adverse effect on endometrium (Fisher et al., 2002

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    Dr Batuhan Özmen completed his residency programme in obstetrics and gynaecology at University of Ankara in 2003, obtaining his certification in reproductive medicine and artificial reproductive techniques in 2005. In 2006, he worked in the Department of Obstetrics and Gynecology of the University of Schleswig-Holstein in Lübeck under the supervision of Professor Safaa Al-Hasani on laboratory applications in reproductive medicine. He is interested in cryopreservation and vitrification of human gametes, reproductive surgery and human sperm DNA damage. He is now working in the Department of Reproductive Endocrinology at the University of Ankara, Turkey.Dr Batuhan Özmen

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