Mild ovarian stimulation

Abstract

Purpose To evaluate the efficacy of using only mild ovarian stimulation protocols for in vitro fertilization. Both groups with decreased and normal ovarian reserve were evaluated. Methods Three different mild stimulation protocols were evaluated: natural with no exogenous follicle stimulation hormone (FSH) drugs at all, natural with a boost of low dose FSH to complete follicular maturation, and minimal stimulation with low dose (75-150IU) FSH from day 3-5 of the menstrual cycle. Ethinyl estradiol was sometimes used to lower high day 3 serum FSH. Results Good pregnancy and implantation rates were found even in those women with elevated serum FSH that could only generate one follicle. Conclusions Mild ovarian stimulation seems preferable to high dose FSH regimens in women with elevated day 3 serum FSH based on previous poor reported pregnancy rates with the latter protocols. Comparable pregnancy rates to high dose regimen were seen in women with normal egg reserve at much lower risk and cost.Background leading to minimal stimulation protocol

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles

“…The "mild" ovarian stimulation strategy, in which a low dose of exogenous gonadotropins is administered from day 4-7 of the menstrual cycle, allows initial follicle recruitment by endogenous FSH [1][2][3][4][5][6]. In women with abundant ovarian follicular reserve, starting FSH on cycle day 4 with a fixed daily dose of 150 IU is sufficient to overcome dominance and finally obtain an average number of 5-12 oocytes [16].…”

“…In human IVF, the protocol of ovarian stimulation in which gonadotropin administration is started at a low dose (100-150 IU/d) on day 4-7 of the menstrual cycle, thus allowing a "natural" recruitment of follicles by endogenous FSH in the early follicular phase, has been addressed as "mild" [1][2][3][4][5][6]. The "mild" stimulation strategy has been proposed as an alternative to the standard "long" stimulation protocol, in which pituitary suppression is obtained in the luteal phase of the run-in cycle and the recruitment of ovarian follicles is achieved by exogenous gonadotropins.…”

Should mild stimulation be the order of the day?

“…It is believed that high doses of FSH recruit “resistant” follicles rescuing them from atresia, but the oocytes that they host are of poor quality and usually do not result in the generation of good quality embryos. [ 24 ]…”

The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response

“…While advanced maternal age is most often implicated, ovarian stimulation of suboptimal follicles, containing poorer quality oocytes that would have otherwise been naturally selected to undergo atresia, has been hypothesized to lead to an increase in oocyte aneuploidy. COH has been proposed to influence oocyte maturation and the completion of meiosis, potentially mediating chromosomal aneuploidy and mosaicism [3]. Based on these theories, an increasing number of fertility centers recently reverted to using minimal stimulation protocols, despite a lack of evidence-based, peerreviewed data to support their efficacy [4].…”