Human Reproduction | 2019
A randomized triple blind controlled trial comparing the live birth rate of IVF following brief incubation versus standard incubation of gametes
Abstract
STUDY QUESTION\nDoes brief incubation of oocytes and spermatozoa improve the live birth rate (LBR) of IVF when compared with that of standard incubation?\n\n\nSUMMARY ANSWER\nBrief incubation of gametes does not improve the LBR of IVF when compared with standard incubation.\n\n\nWHAT IS KNOWN ALREADY\nSome small randomized studies showed that brief incubation was associated with a significantly higher ongoing pregnancy rate than standard incubation.\n\n\nSTUDY DESIGN, SIZE, DURATION\nThis is a randomized triple blind study of 320 infertile women for their first or repeated cycles undergoing IVF between September 2015 and October 2016.\n\n\nPARTICIPANTS/MATERIALS, SETTING, METHODS\nWomen were randomized into the brief incubation group (n = 160) or the standard incubation group (n = 160) according to a computer-generated randomization list. Oocytes were incubated with spermatozoa (0.3-1.2 million motile sperm/ml) for 3-4 h in the brief incubation group while oocytes were incubated with spermatozoa at similar concentration for 20 h in the standard incubation group. The primary outcome was the LBR (a baby born alive after 22 weeks gestation) in the fresh cycle.\n\n\nMAIN RESULTS AND THE ROLE OF CHANCE\nThere was no significant difference in the LBR between the brief and standard incubation groups based on both intention-to-treat [33.0% (53/160) versus 36.8% (59/160), relative risk (RR) 0.898 (95% CI = 0.666-1.212), P = 0.482] and per protocol [41.4%(53/128) versus 41.0% (59/144), RR1.011 (95% CI = 0.760-1.343), P = 0.942] analyses. Clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy and implantation rates were comparable for the two groups. Similar results were found with subgroup analysis of advanced maternal age, abnormal semen analysis and repeated IVF cycles. No differences were observed in cumulative LBR between two groups.\n\n\nLIMITATIONS, REASONS FOR CAUTION\nVarious motile sperm concentrations of 0.3-1.2 million per ml were used for insemination and the reactive oxygen species level in the insemination medium was not measured. The highest level at 1.2 million per ml is still relatively low compared to prior studies, therefore we do not know whether brief incubation can improve the LBR using higher concentrations of spermatozoa. The present sample size may not be adequate to detect a smaller difference in the LBR.\n\n\nWIDER IMPLICATIONS OF THE FINDINGS\nThe present study demonstrated that a brief incubation of gametes had no significant beneficial effect on the LBR when compared with the standard incubation. The practice of brief incubation of gametes is not necessary and this can save the already tight manpower in many laboratories.\n\n\nSTUDY FUNDING/COMPETING INTERESTS\nThe study was supported by the Merck-Serono China Research Fund for Fertility Experts (2015), which was not involved in study design, execution, data analysis and manuscript preparation. There are no conflicts of interest for all authors.\n\n\nTRIAL REGISTRATION NUMBER\nClinicalTrials.gov Identifier NCT02534857.\n\n\nTRIAL REGISTRATION DATE\n28 August 2015.\n\n\nDATE OF FIRST PATIENT’S ENROLMENT\n8 September 2015.