Hyaluronan-enriched transfer medium improves outcome in patients with multiple embryo transfer failures

Abstract

Purpose To ascertain whether the use of hyaluronanenriched transfer medium (HETM) improves pregnancy and implantation rates among embryo transfer patients with a history of multiple implantation failures. Methods Patients (n0314) under the age of 40 and with a history of multiple unsuccessful embryo transfers were enrolled. There were three groups of patients: those undergoing fresh embryo transfer (fresh ET [n 0111]), those undergoing vitrified-warmed ET in the natural cycle (WET-N [n0101]) and those undergoing WET in a hormone replacement cycle ). On the day of ET, patients were randomized to HETM (0.5 mg/ml hyaluronan) or control medium containing no hyaluronan. Only patients with good quality embryos on day 3 were included. Results For all three patients groups (fresh ET, WET-N and WET-H) pregnancy rates (37.5 %, 31.4 % and 41.2 %, respectively) were significantly higher when using HETM compared with control medium (10.9 %, 10.0 % and 15.7 %, respectively; p<0.05), and implantation rates when using HETM were also significantly higher compared with control medium (p<0.05). Miscarriage rates were similar in both groups. Conclusion HETM significantly increased pregnancy and implantation rates among embryo transfer patients with a history of multiple unsuccessful implantations-regardless of method used to prepare the endometrium.

Routine use of EmbryoGlue® as embryo transfer medium does not improve the ART outcomes

“…The ART success rates have been significantly improved over last decades; however, embryo implantation still remains a major limiting factor [1]. It has been considered that composition of an embryo transfer medium is important for interaction between embryo and endometrium at the time of implantation [2].…”

“…Both the endometrium of uterine and embryo express receptors for HA. This binding of HA to the embryo might facilitate its attachment to the uterine endometrium until the embryo grows to a hatched blastocyst [1]. Indeed, HA produce a viscous environment that might enhance ET process, while inhibiting the expulsion of embryos from the uterine cavity after ET [6].…”

“…In addition, some degree of viral protection and antiimmunogenic properties are other characteristics of HA which prohibit the rejection of an embryo from the uterine cavity [7,8]. Based on these data, HA-enriched transfer medium (HETM) became a possible candidate for improving implantation process [1]. Therefore, EmbryoGlue Ò as a HETM was introduced to support embryos at the time of ET for promoting the implantation process [5].…”

Regulation and roles of the hyaluronan system in mammalian reproduction

“…In the human uterus, peak expression of HAS and CD44 is in the mid-secretory stage (Afify et al 2006). There is a plethora of data suggesting the beneficial roles for HA in human embryo implantation (Urman et al 2008, Hambiliki et al 2010, Nakagawa et al 2012. It is thought that implantation failure could be reduced by providing a 'sticky' matrix for the embryos to attach and for this reason HA (which is also called 'magic glue' (Girish & Kemparaju 2007), or EmbryoGlue (Hazlett et al 2008)) is often used as a supplement in human embryo transfer medium.…”

Influence of hyaluronan on endometrial receptivity and embryo attachment in sheep

“…However, the efficiency and controversy of HA remains inconsistent among different studies. In a few studies, HA was shown to be beneficial for embryo implantation (Svobodová et al 2007;Urman et al 2008;Nakagawa et al 2012). Moreover, in attempts to develop human embryo culture media free from blood-derived additives (particularly albumin) HA was successfully used as a sole macromolecule in human embryo transfer medium, which resulted in high pregnancy and implantation rates (Simon 2003).…”