A randomized triple blind controlled trial comparing the live birth rate of IVF following brief incubation versus standard incubation of gametes.

Study Question: Does brief incubation of oocytes and spermatozoa improve the live birth rate (LBR) of IVF when compared with that of standard incubation?

Summary Answer: Brief incubation of gametes does not improve the LBR of IVF when compared with standard incubation.

What Is Known Already: Some small randomized studies showed that brief incubation was associated with a significantly higher ongoing pregnancy rate than standard incubation.

Study Design, Size, Duration: This is a randomized triple blind study of 320 infertile women for their first or repeated cycles undergoing IVF between September 2015 and October 2016.

Participants/materials, Setting, Methods: Women 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.

Main Results And The Role Of Chance: There 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.

Limitations, Reasons For Caution: Various 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.

Wider Implications Of The Findings: The 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.

Study Funding/competing Interests: The 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.

Trial Registration Number: ClinicalTrials.gov Identifier NCT02534857.

Trial Registration Date: 28 August 2015.

Date Of First Patient’s Enrolment: 8 September 2015.