Related Experiment Video
Updated: May 3, 2026

Fertility Preservation Through Oocyte Vitrification: Clinical and Laboratory Perspectives
Published on: September 16, 2021
Mild/minimal stimulation protocol for ovarian stimulation of patients at high risk of developing ovarian
1RISEL-One Day Medical Center, Via Attilio Ambrosini 114, 00147, Rome, Italy, leo.rinaldi@tiscali.it.
Background:
Recently, an increased scientific interest was focused on mild approaches for ovarian stimulation in clinical practice. Milder stimulation aims to develop safer and more patient-friendly protocols which are more physiological, less drug use, less expensive and the risks of treatment are highly minimized.
Aim:
To investigate the efficacy and safety of a mild ovarian stimulation protocol in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS), compared to conventional long down-regulation protocol.
Subjects And Methods:
This a prospective, open, randomized study, included 349 infertile patients considered at high risk of developing OHSS, undergoing in vitro fertilization treatment in two private assisted reproduction centers. The patients were randomized into two groups: group A (n = 148) had a mild/minimal stimulation protocol of recombinant FSH (rFSH) combined with GnRH antagonist. Group B (n = 201) (control group) had a standard long protocol of rFSH combined with GnRH agonist.
Results:
There was no significant difference observed between the two groups regarding the mean number of oocytes retrieved per patient, mature metaphase II oocytes, fertilization rate, and embryo cleavage rate. Significantly higher implantation rate (21.5 vs 14.5 %) (p < 0.05), pregnancy rate (37.7 vs 23.4 %) (p < 0.05), and delivery rate (32.8 vs 20.1 %) (p < 0.05) were observed in favor of groups A compared to group B. Lower proportion of patients (4.7 %), though not statistically significant, has developed OHSS in group A compared to group B (8.4 %).
Conclusion:
Our study shows that mild stimulation regimen is highly effective for ovarian stimulation of patients who have experienced OHSS complication without increasing the risk of OHSS.

