Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study.
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 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm 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.
Battaglia
Cesare
C
Reproductive Medicine Unit, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy. battagli@med.unibo.it
Regnani
Giorgia
G
Marsella
Tiziana
T
Facchinetti
Fabio
F
Volpe
Annibale
A
Venturoli
Stefano
S
Flamigni
Carlo
C
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use; D015571:Follicular Fluid / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D006080:Ovarian Follicle / Q000503:physiopathology; D010062:Ovulation Induction; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D012016:Reference Values
D000277:Adjuvants, Pharmaceutic; D018997:Chorionic Gonadotropin, beta Subunit, Human; D009566:Nitrates; D009573:Nitrites; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; D001120:Arginine