Title: A trial of egg recovery rates for IVF using a collection chamber that provides environmental control: Eggcell Trial.
Funder: Department of Health and Social Care

Abstract: Clinical Intervention We propose a multicentre prospective non-inferiority trial of women undergoing egg collection for IVF comparing the use of Eggcell with the standard procedures. Participants will be undergoing routine IVF. The research nurse will give trial information to potential participants about five days before recruitment. Recruitment (dependent on the number of follicles developing after standard superovulation medication) and randomisation will be 36 h before egg collection. We will recruit women who have 10-20 follicles at the final scan before the egg collection. Women with fewer follicles are excluded to avoid potential compromise of their treatment should the number of eggs collected in Eggcell be reduced. Women with >20 follicles are excluded because it is technically difficult to ensure that all follicles are aspirated in these women. The operator will carry out the procedure with Eggcell or their routine clinic procedure. Consequent patient management will be unchanged. The primary outcome will be the number of eggs recovered related to the number of follicles aspirated. The secondary outcomes will be fertilisation, embryo development, pregnancy rate and live birth rates. There are numerous confounding factors involved in these later outcomes that require complex statistical modelling. We anticipate that the primary outcome will be required for regulatory purposes but that the secondary outcomes will be important for marketing. The trial is powered for the primary outcome only. The clinician and embryologist will complete a questionnaire recording experience with each procedure. Six clinics will be recruited since we need to take account of the minor variations in egg collection procedures in clinical practice to ensure generalisability of the results. Clinical Trial Design and Monitoring. Newcastle Clinical Trials Unit will oversee the conduct of the trial according to regulatory governance and Good Clinical Practice (GCP) procedures. An independent Data Monitoring Committee will be convened to have oversight of the research development, implementation and will also be responsible for monitoring recruitment, patient safety and accumulating data throughout the trial. Statistical Considerations The primary outcome measure of this non-inferiority trial is the egg recovery rate per patient defined as the number of eggs recovered divided by the number of follicles aspirated. The primary analysis is calculation of an unadjusted odds ratio (OR) (95%CI) for the egg recovery rate in the Eggcell group compared to the standard egg collection group. The null hypothesis is that Eggcell is inferior to standard treatment and would lead to an inferior egg recovery rate. Based on Newcastle data, the egg recovery rate with standard treatment is expected to be 68%. Assuming 1 egg fewer per patient is recovered gives a recovery rate of 62.6%. The non-inferiority margin is defined as the OR associated with a presumed loss of 1 egg per patient, thus is 0.79. If the lower end of a 95% confidence interval for the OR is above 0.79, the null hypothesis of inferiority would be rejected. Sample size calculations are based upon simulations using Newcastle data. A beta-binomial model is used for the recovery rate to allow for extra binomial variation across patients. Assuming no difference in the recovery rates between treatment groups (OR=1), 362 patients per treatment group (724 in total) would be required to give 90% power to reject the null hypothesis of inferiority. Secondary outcome rates will be based on calculating risk estimates adjusted by important baseline clinical characteristics at randomisation, to be specified fully in a Statistical Analysis Plan.

Lay abstract: IVF gives over 60,000 subfertile couples the chance of a baby every year in the UK. The average chance of a birth with each procedure is about 25%; it is known that the main factor that determines the outcome is egg quality. We have developed a device that aims to improve the chances that each egg will make a normal embryo increasing the chances of a baby. In normal IVF a needle is passed through the vagina into the ovary. Fluid containing the eggs is aspirated through this needle and attached tubing into a test tube which is then carried into the laboratory. During this process the eggs are exposed to changes in temperature, acidity and may come into contact with any toxic substances in the air. There is evidence that such variations can reduce the chances that the egg will fertilise normally. In a previous grant we developed Eggcell"; a sealed chamber containing warm fluid. Fluid from the ovary that contains the eggs passes directly from the needle and tubing into this protected stable environment. We have tested Eggcell in a research setting but now want to test it in the clinic. Each egg in the ovary grows in a follicle. The average chance of recovering the egg from each follicle aspirated is ~68%. An important indicator of potential successful treatment is the number of eggs collected for each woman. It is important therefore to ensure that Eggcell does not compromise the recovery rate of eggs compared with standard procedures. This proposal is to carry out a clinical trial to determine the recovery rate of eggs per follicle aspirated from the ovary. It will compare the use of Eggcell with the current test tube method. We will look at fertilisation rates, the quality of subsequent embryos and treatment outcome."

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH