Ganirelix acetate causes a rapid reduction in estradiol levels without adversely affecting oocyte maturation in women pretreated with leuprolide acetate who are at risk of ovarian hyperstimulation syndrome.
BACKGROUND
Elevated estradiol (E(2)) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels and avoid cycle cancellation.


METHODS
Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage.


RESULTS
In the treatment group, there was a significant, reproducible reduction in serum E(2) levels. Mean E(2) at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy.


CONCLUSIONS
GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E(2) without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS.
Gustofson
Robert L
RL
Reproductive Endocrinology and Infertility, NIH, Bethesda, MD, USA.
Segars
James H
JH
Larsen
Frederick W
FW
D000328:Adult; D004958:Estradiol / Q000097:blood*; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use; D005306:Fertilization; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D016471:Ovarian Hyperstimulation Syndrome / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012016:Reference Values; D012189:Retrospective Studies
D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016729:Leuprolide; C061018:ganirelix