Hum. Reprod. Advance Access originally published online on January 4, 2007
Human Reproduction 2007 22(4):980-988; doi:10.1093/humrep/del484
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Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial
1 Department of Reproductive Medicine and Gynaecology, University Medical Center, Utrecht, The Netherlands 2 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology 3 Department of Public Health 4 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands 5 Department of Obstetrics and Gynaecology, Medical Center Rijnmond Zuid, Rotterdam, The Netherlands
6 To whom correspondence should be addressed at: Department of Reproductive Medicine and Gynecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Tel.: +31 30 250 1443; Fax: +31 30 250 5433; E-mail: e.b.baart{at}umcutrecht.nl
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.
Key words: aneuploidy/embryo quality/in-vitro fertilization/ovarian stimulation/preimplantation genetic screening
Submitted on August 23, 2006; resubmitted on October 17, 2006; resubmitted on November 8, 2006; accepted on November 29, 2006.
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