"Mild" vs. "long" protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial.
BACKGROUND
This large prospective, randomized study was designed to compare the "mild" protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the "long" protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF.


METHODS
A total of 695 women with clinical, endocrine and ultrasound characteristics suggesting a low ovarian reserve and a poor responsiveness to COH were recruited and randomly assigned to receive the CC/Gn/GnRH-ant "mild" protocol (mild group, n = 355) or the "long" protocol with high-dose Gn (long group, n = 340).


RESULTS
The "mild" stimulation led to significantly shorter follicular phase, lower consumption of exogenous Gn and lower peak estradiol level than the "long" regimen. With the "long" protocol, significantly less cycles were cancelled due to the lack of ovarian response; further, it obtained significantly more oocytes, more mature oocytes, more embryos, and a thicker endometrium. As for the final IVF outcome, however, the two stimulation regimens obtained comparable implantation rate, clinical pregnancy rate, and ongoing pregnancy rate at 12 weeks.


CONCLUSIONS
In conclusion, the "mild" CC/Gn/GnRH-ant stimulation protocol is a valid alternative to the long protocol with high Gn dose as it obtains a comparable success rate and requires significantly less medications, with an obvious economical advantage.
Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, University of Torino, St. Anna Hospital, via Ventimiglia 3, 10126, Torino, Italy, AERRE99@YAHOO.COM.
Alberto
A
Revelli
Alessandra
A
Chiadò
Paola
P
Dalmasso
Veronica
V
Stabile
Francesca
F
Evangelista
Gemma
G
Basso
Chiara
C
Benedetto
D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage; D004624:Embryo Transfer / Q000379:methods; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006062:Gonadotropins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D006801:Humans; D009865:Oocytes / Q000187:drug effects*; D016471:Ovarian Hyperstimulation Syndrome / Q000188:drug therapy* / Q000473:pathology; D010062:Ovulation Induction; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies
D006062:Gonadotropins; D002996:Clomiphene