Hyaluronan-enriched embryo transfer medium for frozen-thawed embryo transfer: a double-blind randomised controlled trial

Abstract

Study question: Does the use of hyaluronan-enriched embryo transfer medium (HETM) improve the live birth rate of frozen-thawed embryo transfer (FET) compared to standard medium? Summary answer:The use of HETM compared to control does not improve the live birth rate of FET. What is known already: Some studies suggest that the use of HETM when compared to transfer medium containing low or no hyaluronan improved clinical pregnancy and live birth rates of in-vitro fertilization (IVF). However, data on FET are limited. Study design, size, duration: We performed a double-blind randomised controlled trial involving 550 women undergoing FET in two centres from April 2016 to April 2018. The sample size was chosen to detect a difference of 12% in the live birth rate with a power of 80% and type I error of 0.05. Women with donor oocyte/embryo treatment or pre-implantation genetic testing were excluded. Participants/materials, setting,methods:Women under the age of 43 at the time of IVF undergoing FET were randomised into two groups in a 1:1 ratio: HETM group and control group. The HETM group used HETM (hyaluronan concentration 0.5 mg/ml) while the control group used a conventional medium (hyaluronan concentration 0.125 mg/ml). Up to two embryos/ blastocysts were replaced. Each woman took part once only. The primary outcome was the live birth rate per randomised woman. Main results and the role of chance: Basic characteristics including age of women, BMI, and number of embryos replaced were comparable in the two groups. Thirteen women (8 in HETM group, 5 in control group) did not have FET because the embryos did not survive upon thawing. One woman in the HETM group had FET cancelled due to fever. One in the HETM group withdrew after randomisation and received conventional medium. All 550 women were included in the intention-to-treat analysis, with a mean of 1.4 embryos/blastocysts transferred in both groups. The live birth rate per randomised woman was 25.5% (70/275) in the HETM group versus 25.5% (70/275) in the control group (p = 1.00). The clinical pregnancy rate was 34.2% (94/275) in both groups (p = 1.00). The multiple pregnancy rate was 13.8% (13/94) in the HETM group versus 19.1% (18/94) in the control group (p = 0.33). One ectopic pregnancy occurred in each group. Other secondary outcomes including on-going pregnancy rate, miscarriage rate and incidence of obstetric complications were similar between the two groups. Subgroup analyses for different embryo stage (cleavage stage embryos versus blastocysts) and different types of endometrial preparation showed no statistically significant difference in the live birth rate between the two groups. Limitations, reasons for caution: The study assessed the role of HETM in an unselected population of infertile women. While this made the results generalizable to the general infertile population, the results did not address specific population e.g. women with recurrent implantation failure. Wider implications of the findings:In this study, the use of HETM did not improve the live birth rate following FET. Trial registration number:ClincialTrials.gov: NCT02725827