Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.

BACKGROUND An efficient oocyte cryopreservation method is mandatory to establish a successful egg-banking programme. Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation, there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking. In this study, we aimed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. METHODS A randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial (NCT00785993), including 600 recipients (alpha = 0.05 and power of 80% for sample-size calculation) selected among 1032 eligible patients from November 2008 to September 2009, was designed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. The study was designed to establish the superiority of the ongoing pregnancy rate (OPR) of fresh oocytes over that of vitrified oocytes, by performing a likelihood ratio test in a logistic regression analysis expressed as odds ratio (OR) with 95% confidence interval (CI). A limit of 0.66 for OR of vitrified versus fresh groups was defined to set up a possible conversion from superiority to non-inferiority. Randomization was performed 1:1 based on a computer randomization list in vitrification (n = 300) or fresh groups (n = 300). The primary end-point was the OPR per randomized patient i.e. intention-to-treat population (ITT). Secondary end-points were clinical pregnancy (CPR), implantation (IR) and fertilization rates, respectively. Additionally, embryo developmental characteristics were recorded. RESULTS There were no differences in donor ovarian stimulation parameters, demographic baseline characteristics for donors and recipients, ovum donation indications or male factor distribution between groups (NS). The OPR per ITT was 43.7 and 41.7% in the vitrification and fresh groups, respectively. The OR of OPR was 0.921 in favour of the vitrification group. Nevertheless, the 95% CI was 0.667-1.274, thus the superiority of fresh group with respect to OPR was not proven (P = 0.744). Non-inferiority of the vitrified group compared with the fresh group was shown with a margin of 0.667, which was above the pre-established non-inferiority limit of 0.66. CPR per cycle (50.2 versus 49.8%; P = 0.933) or per embryo-transfer (55.4 versus 55.6% ; P = 0.974), and IR (39.9 versus 40.9%; P = 0.745) were similar for patients receiving either vitrified or fresh oocytes. The proportion of top-quality embryos obtained either by inseminated oocyte (30.8 versus 30.8% for Day-2; and 36.1 versus 37.7% for Day-3, respectively) or by cleaved embryos (43.6 versus 43.8% for Day-2 and 58.4 versus 60.7% for Day-3, respectively) was similar between groups (NS). CONCLUSIONS This controlled-randomized, clinical trial confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme, failing to demonstrate the superiority of using fresh oocytes with respect to the use of vitrified egg-banked ones in terms of OPR. Instead, the non-inferiority of vitrified oocytes was confirmed. These findings involve highly relevant issues that may open a new range of possibilities in ART.