Evaluating the role of hyaluronic acid products in the treatment of infertility

Maree, Lara (2017-03)

Thesis (MMed)--Stellenbosch University, 2017.

Thesis

ENGLISH SUMMARY: Hyaluronic acid is (HA) a naturally existing macromolecule and present in several HA based products aiming to improve the outcomes of assisted reproduction. Hyaluronic acid is produced by the human cumulus cells and is therefore naturally present in the female reproductive tract. During physiological intracytoplasmic sperm injection (PICSI®), spermatozoa that are able to bind to solid-state HA, have a chromatin structure with high DNA chain integrity associated with fertilization competence and normal chromosomal constitution. The addition of HA into transfer media is based on several properties that characterize it as an implantation-enhancing molecule. Its viscosity is believed to facilitate the integration of the embryos into the fluid secretions of the intrauterine environment as it has been shown to increase cell-to-cell and cell-to-matrix adhesion. The presence of the CD44 receptor for HA, expressed on both the embryo and the supporting network of the human endometrium, suggests the action of HA during the process of implantation. The aim of the study was to evaluate retrospectively the role of hyaluronic acid in the PICSI® procedure and prospectively also its use in embryo transfer medium. The retrospective study involved the review of 388 patients whose treatment involved the fertilization of their ova by either physiological intracytoplasmic sperm injection (PICSI®) or traditional intracytoplasmic sperm injection (ICSI). In vitro fertilization (IVF) was used as a control group. PICSI® involves the use of a specialised culture dish that has three gel-like microdots of HA attached to the bottom surface of its interior. These HA dots provide an additional parameter whereby spermatozoa with a normal chromosome composition can be selected for injection. Strict exclusion criteria were applied to eliminate variables other than the fertilization method that could have influenced treatment outcomes. The comparison showed no statistically significant improvement in ART outcome, at Drs Aevitas Fertility Clinic (Vincent Pallotti Hospital, Pinelands, South Africa), when PICSI® dishes were used to select spermatozoa for injection. Outcomes measured included; fertilization rate, embryo quality, pregnancy and miscarriage rates. The prospective study evaluated the treatment outcomes of patients who underwent embryo transfer with specialized embryo transfer medium, EmbryoGlue® (EG) in comparison with a historically similar patient population who underwent embryo transfer with traditionally employed culture media at the same clinic (Drs Aevitas Fertility Clinic). The HA contained in EG acts as a specialised adherence compound supporting the implantation of a transferred embryo in the endometrium. The comparison showed no statistically significant improvement in clinical pregnancy, ongoing clinical pregnancy nor in miscarriage rates when adjustments were made for confounding factors. The results of the study have produced valuable information that will inform future use of HA products in the treatment of patients attending Drs Aevitas Fertility Clinic.

AFRIKAANS OPSOMMING: Die makromolekule, hualuroonsuur (HS), wat natuurlik voorkom, is teenwoordig in verskeie produkte wat die uitkoms van geassisteerde reproduktiewe tegnieke (GAT) kan verbeter. Hualuroonsuur word deur menslike kumulusselle geproduseer en is dus natuurlik teenwoordig in die vroulike reproduktiewe traktus. Tydens fisiologiese intrasitoplasmatiese sperm inspuiting (PICSI®), bind spermatosoa met hoë DNA integriteit, wat geassossieer word met bevrugtingspotensiaal en normale chromosomale samestelling, aan die hualoroonsuur in gelvorm. Die byvoeging van hualoroonsuur in embrio terugplasingsmedia word gebasseer op die eienskap dat die viskositeit van hualoroonsuur die integrasie van die embrio met die sekresies van die intra-uteriene holte en dus ook inplantasie bevorder. Dit word toegeskryf aan beter sel tot sel en sel tot matriks adhesie. Die teenwoordigheid van CD44 reseptore vir HA, teenwoordig op beide die embrio en die endometrium, bevestig die rol van hualoroonsuur tydens die inplantasie proses. Die doel van die studie was om die rol van hualoroonsuur tydens die PICSI® prosedure sowel as die embrio terugplasingsprosedure te bepaal. Die restrospektiewe studie, wat 388 pasiente ingesluit het, het gepoog om die produk PICSI® wat hualoroonsuur bevat, te vergelyk met klasieke intrasitoplasmatiese sperm inspuiting [ICSI]. Die kontrole groep was pasiente wat met behulp van die in vitro bevrugtings metode [IVB] behandel is. Tydens die PICSI® prodsedure word ‘n gespesialiseerde kultuur bakkie, wat drie druppels HS in gelvorm op die oppervlak bevat, gebruik. Hierdie hualoroondruppels bied die voordeel dat spermselle met normale chromosoomsamestelling geselekteer kan word. Streng uitsluitingskriteria is toegepas om alle ander veranderlikes wat uitkoms kan beïnvloed, te elimineer. Die vergelyking van data by die Drs Aevitas fertiliteitskliniek (Vincent Pallotti Hospitaal, Pinelands, Suid Afrika),het geen statisties beduidende verbetering in uitkoms tydens die PICSI® prosedure aangedui nie. Uitkoms is gemeet aan persentasie bevrugting, embriokwaliteit, swangerskap- en miskraam koers. Die prospektiewe studie het die behandelingsuitkoms tussen pasiente wat embrioterugplasing ondergaan het met EmbryoGlue® (EG) medium en histories soortgelyke pasiente wat histories embrioterugplasings ondergaan het met tradisionele kultuur medium, by dieselfde kliniek (Drs Aevitas fertiliteitskliniek) vergelyk. Die EG medium bevat hualoroonsuur wat volgens studies implantasie van die embrios bevorder. Die resultate het, na aanpassing van strengelveranderlike faktore, geen stasties beduidende verbetering in kliniese swangerskap, voortgaande swangerskap of miskraam koers tydens die gebruik van die EG medium aangedui nie. Die resultate van die studie het waardevolle inligting rakende toekomstige gebruik van HS produkte tydens die behandeling van pasiente by die Drs Aevitas fertiliteitskliniek verskaf.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/101110
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