Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.
BACKGROUND
To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens.


METHODS
Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres.


RESULTS
The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors.


CONCLUSIONS
Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.
Baart
Esther B
EB
Department of Reproductive Medicine and Gynaecology, University Medical Center, Utrecht, The Netherlands. e.b.baart@umcutrecht.nl
Martini
Elena
E
Eijkemans
Marinus J
MJ
Van Opstal
Diane
D
Beckers
Nicole G M
NG
Verhoeff
Arie
A
Macklon
Nicolas S
NS
Fauser
Bart C J M
BC
D000328:Adult; D000782:Aneuploidy; D001706:Biopsy; D001755:Blastocyst; D001757:Blastomeres / Q000648:ultrastructure; D002875:Chromosomes / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D010062:Ovulation Induction / Q000379:methods*; D019836:Preimplantation Diagnosis; D016896:Treatment Outcome