Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols

• Published in: Human reproduction (Oxford) 2006-10, Vol.21 (10), p.2593-2600
• Main Authors: Lossl, K., Andersen, A.N., Loft, A., Freiesleben, N.L.C., Bangsbøll, S., Andersen, C.Yding
• Format: Article
• Language: English
• Subjects: Adult; androgen priming; Aromatase - metabolism; aromatase inhibitor; Biological and medical sciences; Chorionic Gonadotropin - pharmacology; Enzyme Inhibitors - pharmacology; Female; Fertilization in Vitro; follicular fluid; Follicular Phase - drug effects; Follicular Phase - physiology; GnRH antagonist; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropin-Releasing Hormone - therapeutic use; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Menstrual Cycle - drug effects; Menstrual Cycle - physiology; Nitriles - therapeutic use; Ovarian Follicle - drug effects; Ovarian Follicle - physiology; ovarian stimulation; Patient Selection; Sperm Injections, Intracytoplasmic; Triazoles - therapeutic use
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/del221

BACKGROUND: Temporary exposure of follicles to increased levels of androgens may enhance their sensitivity to FSH. The aim of this study was to increase the intraovarian androgen level using aromatase inhibitors and hCG before controlled ovarian stimulation (COH) and to test this concept clinically. METHODS: In a prospective, non-randomized study, 45 patients were treated in modified antagonist protocols including early-follicular-phase down-regulation and androgen priming before COH. All patients received cetrorelix, 3 mg s.c., on cycle days 2 and 5. Group I (n = 15) received no other pretreatment. Group II (n = 15) received 1 daily tablet of aromatase inhibitor, letrozole 2.5 mg, from cycle days 2 to 8. Group III (n = 15) received letrozole as Group II and 1250 IU of hCG s.c. on cycle day 2. From cycle day 8, all patients were stimulated with highly purified menotrophin in a flexible antagonist protocol. RESULTS: Aromatase inhibitor increased the level of testosterone in follicular fluid (P < 0.002), but not in plasma. Androgen priming with aromatase inhibitor and hCG increased the number of good-quality embryos (P = 0.015) but did not increase the implantation rate. CONCLUSIONS: The use of aromatase inhibitor before COH significantly influences the local endocrine environment before and during stimulation. Androgen priming with both aromatase inhibitor and hCG may result in more good-quality embryos.