Human Reproduction, Vol. 17, No. 3, 659-665,
March 2002
© 2002 European Society of Human Reproduction and Embryology
Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study
1 Reproductive Medicine Unit and 2 Department of Obstetrics and Gynaecology, University of Bologna and 3 Department of Obstetrics and Gynaecology, University of Modena, Italy
BACKGROUND: Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation. METHODS: To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored. RESULTS: Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 ± 12 µmol to 279 ± 31 µmol (P = 0.002) on the day of ß-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles 
17 mm was lower (P = 0.038) in group I than group II. The `good quality' embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = –0.613; P = 0.005) and perifollicular artery pulsatility index (r = –0.609; P = 0.021). CONCLUSIONS: L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.
Key words: controlled ovarian hyperstimulation/Doppler/IVF/L-arginine/nitric oxide
4 To whom correspondence should be addressed at: 1st Department of Obstetrics and Gynaecology–Reproductive Medicine Unit, University of Bologna, Via Massarenti, 13 40138 Bologna, Italy. E-mail: battagli{at}med.unibo.it
Submitted on February 2, 2001; resubmitted on August 3, 2001
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