The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells .

STUDY QUESTION

Does embryo transfer medium containing hyaluronate (HA) promote the attachment phase of human embryo implantation?

SUMMARY ANSWER

HA-containing medium does not promote human blastocyst attachment to endometrial epithelial cells .

WHAT IS KNOWN ALREADY

Embryo transfer media containing high concentrations of HA are being used to increase implantation and live birth rates in IVF treatment, although the mechanism of action is unknown.

STUDY DESIGN SIZE DURATION

Expression of HA-interacting genes in frozen-thawed oocytes/embryos was assessed by microarray analysis ( = 21). Fresh and frozen human blastocysts ( = 98) were co-cultured with human endometrial epithelial Ishikawa cell layers. Blastocyst attachment and the effects of a widely used HA-containing medium were measured.

PARTICIPANTS/MATERIALS SETTING METHODS: Human embryos surplus to treatment requirements were donated with informed consent from several ART centres. Blastocyst-stage embryos were transferred at day 6 to confluent Ishikawa cell layers; some blastocysts were artificially hatched. Blastocyst attachment was monitored from 1 to 48 h, and the effects of blastocyst pre-treatment for 10 min with HA-containing medium were determined.

MAIN RESULTS AND THE ROLE OF CHANCE

Human embryos expressed the HA receptor genes and , hyaluronan synthase genes , and hyaluronidase genes , at all stages of preimplantation development. Attachment of partially hatched blastocysts to Ishikawa cells at 24 and 48 h was related to trophectoderm grade ( = 0.0004 and 0.007, respectively,  = 34). Blastocysts of varying clinical grades that had been artificially hatched were all attached within 48 h ( = 21). Treatment of artificially hatched blastocysts with HA-containing medium did not significantly affect attachment at early (1-6 h) or late (24 and 48 h) time points, compared with control blastocysts ( = 43).

LIMITATIONS REASONS FOR CAUTION

Using an adenocarcinoma-derived cell line to model embryo-endometrium attachment may not fully recapitulate interactions. The high levels of blastocyst attachment seen with this model may limit the sensitivity with which the effects of HA can be observed.

WIDER IMPLICATIONS OF THE FINDINGS

Morphological trophectoderm grade can be correlated with blastocyst attachment . HA-containing medium may increase pregnancy rates by mechanisms other than promoting blastocyst attachment to endometrium.

STUDY FUNDING/COMPETING INTERESTS: This work was funded by a grant from the Wellbeing of Women, the NIHR Local Comprehensive Research Network and NIHR Manchester Clinical Research Facility, the Department of Health Scientist Practitioner Training Scheme, and the Ministry of Higher Education, The State of Libya. None of the authors has any conflict of interest to declare.