Studies on in vitro fertilised human preembryos. Morphological and chromosomal aspects

Abstract: The success rate of in vitro fertilisation (IVF) has gradually increased due to basic research in preembryonic biology and the introduction of new methods, both technical and medical. However, further research is needed to establish which preembryos are developmentally most competent in order to be able to maintain the pregnancy rate while only a single preembryo is being transferred.In this thesis human gametes and preembryos were studied from the oocyte to the blastocyst stage with emphasis on both morphology and chromosomal status. The main purpose was to increase our understanding of the specific conditions for gametes and preembryos produced by IVF, and use this knowledge to improve our possibilities to select the preembryo with the highest chance of implanting in the uterus and develop into a healthy child.Four different developmental stages were studied:Oocyte stage: By using immunohistochemical methods it was found that the second metaphase spindle which is produced during the second meiotic division (meiosis II) is not - as previously believed - always positioned directly under the first polar body (PB). These findings can have important implications for the safety of both IVF techniques such as intracytoplasmic sperm injectons (ICSI) and other related techniques.First cleavage stage: We compared early cleaved preembryos to late cleaving preembryos in regard to pregnancy, implantation and birth rates. It was found that early cleaved preembryos had a higher biological competence than preembryos that cleaved late. Furthermore, we found that this parameter could be used to select the most optimal preembryo for embryo transfer after ICSI.Early cleavage stage: Cleavage stage preembryos with cells of uneven size versus even size were compared in regard to pregnancy/implantation rates as well as the occurrence of chromosomal aberrations. It was found that preembryos with uneven sized cells had significantly lower pregnancy/implantation rates and that this could partially be explained by a higher degree of chromosomal abnormalities. Blastocyst stage: Preembryos considered morphologically suboptimal at the four to eight cell stage, were cultured to the blastocyst stage. The aim was to study the chromosomal status of these blastocysts. As a control group we used preembryos of good morphological quality that had been frozen-stored and were not intended for transfer to the patient. It was found that blastocysts from suboptimal preembryos were of lower quality, both morphologically and chromosomally, than blastocysts from preembryos of good quality. These findings indicate that morphological scoring is of great importance but furthermore that many of the morphologically suboptimal preembryos have the potential to reach the blastocyst stage.In conclusion, this thesis shows that basic research that goes hand in hand with clinical work can lead to valuable findings which can rapidly be implemented into clinical practice. At the same time, it demonstrates the need for further studies to increase our understanding of the many, still unknown, factors in early human preembryonic development.

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