In this preliminary prospective randomized study of 420 patients undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI), 17 patients (4%) developed moderate to severe ovarian hyperstimulation syndrome (OHSS). Re-evaluation for OHSS on day 4 and 6 after oocyte retrieval identified one patient with continuous risk for severe OHSS, resulting in cancellation of the transfer (1/17, 5.8%). Prospectively, two of three patients had the zona pellucida of the blastocyst removed by pronase exposure prior to transfer. Significantly more patients became pregnant when a zona-free blastocyst was transferred in comparison to transfer of a single zona-intact embryo (9/11 or 82% versus 1/5 or 20%; P < 0.01). Higher ongoing singleton pregnancy rates were obtained when the zona pellucida was removed prior to the transfer (6/11 and 1/5 respectively). This preliminary prospective randomized study indicates that by prolonging the evaluation time for patients at risk of developing OHSS for up to 6 days after the oocyte retrieval, those patients at risk for developing severe OHSS can be identified. Transferring a single zona-free day 5 embryo (blastocyst) and freezing of the supernumerary embryos offers the patient with moderate OHSS an optimal chance for a singleton pregnancy, while avoiding the serious maternal complications of ovarian hyperstimulation syndrome.