Estimation of embryo transfer media viscosity and consideration of its effect on media and uterine fluid interactions

Reed, Michael L.; Said, Al-Hasen

doi:10.1016/j.rbmo.2019.07.034

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…Indeed, we show that hTSC NV HBEGF and NVs, enriched in these molecules, are effective supplements for promoting endometrial adhesion to trophectodermal cells and trophectodermal invasion into Matrigel (Figure 5). For example, they may be paired with clinically available supplements such as EmbryoGlue, a viscous embryo transfer media which minimises embryo mobility [111,112], supports embryo health [113], and which hyaluronan content promotes interactions with CD44 [114], purported to enhance implantation [112,115] and live birth [116][117][118][119] rates by 7%-9%. Like gelatin methacryloyl-rich hydrogels [120][121][122], they may serve to prolong the stability and function of NVs.…”

Section: Discussionmentioning

confidence: 99%

HB‐EGF‐loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

Poh,

Rai,

Cross

et al. 2024

Proteomics

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The ability of trophectodermal cells (outer layer of the embryo) to attach to the endometrial cells and subsequently invade the underlying matrix are critical stages of embryo implantation during successful pregnancy establishment. Extracellular vesicles (EVs) have been implicated in embryo‐maternal crosstalk, capable of reprogramming endometrial cells towards a pro‐implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limit their therapeutic potential. We have previously established generation of cell‐derived nanovesicles (NVs) from human trophectodermal cells (hTSCs) and their capacity to reprogram endometrial cells to enhance adhesion and blastocyst outgrowth. Here, we employed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB‐EGF (NVHBEGF). We show these loaded NVs elicit EGFR‐mediated effects in recipient endometrial cells, activating kinase phosphorylation sites that modulate their activity (AKT S124/129, MAPK1 T185/Y187), and downstream signalling pathways and processes (AKT signal transduction, GTPase activity). Importantly, they enhanced target cell attachment and invasion. The phosphoproteomics and proteomics approach highlight NVHBEGF‐mediated short‐term signalling patterns and long‐term reprogramming capabilities on endometrial cells which functionally enhance trophectodermal‐endometrial interactions. This proof‐of‐concept study demonstrates feasibility in enhancing the functional potency of NVs in the context of embryo implantation.

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Section: Discussionmentioning

confidence: 99%

HB‐EGF‐loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

Poh,

Rai,

Cross

et al. 2024

Proteomics

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show abstract

“…Currently, a clinically available supplement beneficial to both embryo and endometrium is EmbryoGlue, a viscous, hyaluronan-rich media purported to marginally increase implantation [166,167] and live birth [168][169][170][171] rates by 7%-9% by minimising embryo mobility [167,172], supporting embryo health [173], and promoting initial embryo-endometrial attachment via hyaluronate-CD44 interaction [81]. Given its viscosity, EmbryoGlue may function similarly to gelatin methacryloyl-rich hydrogels used to prolong the stability and function of EVs [174][175][176], without immobilising the implanting embryo.…”

Section: Discussionmentioning

confidence: 99%

Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

Poh,

Rai,

Pangestu

et al. 2023

Proteomics

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Extracellular vesicles (EVs) are important mediators of embryo attachment and outgrowth critical for successful implantation. While EVs have garnered immense interest in their therapeutic potential in assisted reproductive technology by improving implantation success, their large‐scale generation remains a major challenge. Here, we report a rapid and scalable production of nanovesicles (NVs) directly from human trophectoderm cells (hTSCs) via serial mechanical extrusion of cells; these NVs can be generated in approximately 6 h with a 20‐fold higher yield than EVs isolated from culture medium of the same number of cells. NVs display similar biophysical traits (morphologically intact, spherical, 90–130 nm) to EVs, and are laden with hallmark players of implantation that include cell‐matrix adhesion and extracellular matrix organisation proteins (ITGA2/V, ITGB1, MFGE8) and antioxidative regulators (PRDX1, SOD2). Functionally, NVs are readily taken up by low‐receptive endometrial HEC1A cells and reprogram their proteome towards a receptive phenotype that support hTSC spheroid attachment. Moreover, a single dose treatment with NVs significantly enhanced adhesion and spreading of mouse embryo trophoblast on fibronectin matrix. Thus, we demonstrate the functional potential of NVs in enhancing embryo implantation and highlight their rapid and scalable generation, amenable to clinical utility.

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

Ruane

Buck

Babbington

et al. 2020

Human Reproduction Open

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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 in vitro. 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 (n = 21). Fresh and frozen human blastocysts (n = 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 CD44 and HMMR, hyaluronan synthase genes HAS1–3, and hyaluronidase genes HYAL1–3, at all stages of preimplantation development. Attachment of partially hatched blastocysts to Ishikawa cells at 24 and 48 h was related to trophectoderm grade (P = 0.0004 and 0.007, respectively, n = 34). Blastocysts of varying clinical grades that had been artificially hatched were all attached within 48 h (n = 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 (n = 43). LIMITATIONS, REASONS FOR CAUTION Using an adenocarcinoma-derived cell line to model embryo-endometrium attachment may not fully recapitulate in vivo interactions. The high levels of blastocyst attachment seen with this in vitro 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 in vitro. HA-containing medium may increase pregnancy rates by mechanisms other than promoting blastocyst attachment to endometrium. STUDY FUNDING/COMPETING INTEREST(S) 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.

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Estimation of embryo transfer media viscosity and consideration of its effect on media and uterine fluid interactions

Cited by 3 publications

References 52 publications

HB‐EGF‐loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

HB‐EGF‐loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

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

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