Biological Influences on the Cytogenetics of Early Human Development: An IVF Study

Jamieson, Mary Elizabeth (1992) Biological Influences on the Cytogenetics of Early Human Development: An IVF Study. PhD thesis, University of Glasgow.

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This study investigated the cytogenetics of human oocytes and early embryos and related the findings to maternal factors and aspects of IVF methodology. Chromosome analyses supplemented embryological assessments in evaluation of the effects of luteinising hormone (LH) during follicular growth, the interval from administration of human chorionic gonadotrophin (hCG) to ovulation, the relative effects of in vivo and in vitro oocyte maturation and correlations between follicular and oocyte maturity. Embryo quality assessed by morphology (score 1-10) and growth rate (embryo development rating; EDR, 'ideal' = 100) was predictive of implantation potential but not diagnostic. The mean score of embryos which implanted (8.84) was significantly higher (p<0.001) than those which failed to implant (8.07) and the minimum score associated with pregnancy was seven. Implanting embryos had a significantly higher (p<0.002) mean EDR (101.34) than those which failed to establish pregnancy (96.64). Assessment on day 3 after insemination allowed observation of a larger spectrum of development rate but observations on day 2 were highly predictive (p<0.001) of both assessment parameters on day 3 and no advantage of delayed embryo transfer (ET) was seen in pregnancy rates (day 2, 16.9%; day 3, 16.4%). Suppression of endogenous pituitary function by adjuvant treatment with a gonadotrophin-releasing hormone analog (GnRH-a) during ovarian stimulation with human menopausal gonadotrophin (hMG) eliminated LH fluctuations and surges and all initiated cycles (n=32) proceeded to oocyte retrieval (OR) without complication. The cancellation rate (24/75; 32.0%) was significantly higher (p<0.001) in hMG alone cycles. Pregnancy rates after ET in the two groups (GnRH-a/hMG, 19.3%; hMG, 18.1%) confirmed that embryo quality was similar after both stimulation protocols. Post-mature (PM) oocytes were recovered from 10 hMG alone cycles and were absent (p<0.01) in analog treated cycles. Significantly fewer (p<0.01) oocytes cleaved in PM associated (37.7%) than unaffected (60.4%) cycles although not all oocytes were affected. Prior to hCG administration, all PM cycles showed an attenuated LH surge which was undetected by monitoring of serum progesterone concentrations. A preliminary study investigated the interval between administration of hCG and ovulation in 73 women undergoing laparoscopic OR after ovarian stimulation with hMG and adjuvant GnRH-a. The earliest ovulation was observed at 39.5 hours and oocyte quality, assessed by cumulus expansion and fertilisation rates, improved with extended in vivo maturation (mature oocytes, 36h, 85.7%: fertilisation rate, 36h, 75.8%). These data indicated that extension of the luteinisation to oocyte retrieval delay (LORD) could be practiced with benefits at the level of the oocyte. It is standard IVF practice to preincubate oocytes for 4- 6h before insemination to minimise the incidence of polyspermic fertilisation and maximise embryo quality. The above study was extended to compare the relative effects of in vivo and iri vitro maturation in 60 women randomly allocated to 34 or 39h LORDs. Each patient's oocytes were alternated between immediate insemination and 5h preincubation. The incidence of polyspermic fertilisation was highest in oocytes inseminated immediately after a short LORD (17/100) and was significantly reduced (p<0.05) by preincubation and/or an extended LORD. Fertilisation rates were significantly higher (p<0.05) after a 39h (84.2%) than a 34h LORD (76.8%) and the incidence of delayed fertilisation was reduced by extension of the in vivo maturation time (34h, 12.9%; 39h, 3.9%; p<0.001). The relative importance of follicle size and cumulus expansion as indicators of oocyte maturity was investigated by retrospective analysis of IVF data on 6922 oocytes. Cleavage rates and embryo quality were significantly better (p2.5ml of follicle fluid; 63.4% cleaved, mean score 7.69) than a small follicle (<2.5ml; 51.3% cleaved, mean score 7.22). Significantly higher (p<0.001) cleavage rates were observed if the associated cumulus was fully expanded (79.2%) than if the oocyte was scored as immature (73.8%); embryo quality was unaffected. The two parameters of assessment were not independent but combined data revealed that follicle size was a better indicator of fertilisation potential and subsequent embryo quality than cumulus expansion. This study detected a high incidence of chromosome abnormalities in human oocytes and preimplantation embryos. In vitro fertilisation methodology influenced oocyte maturity and IVF success rates but did not affect the frequency of aneuploidy. Factors influencing maternal meiotic nondisjunction require further investigation but this fundamental aspect of human reproduction is likely to be a limiting factor in the success of assisted conception treatments. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: J R T Coutts
Keywords: Genetics, Developmental biology
Date of Award: 1992
Depositing User: Enlighten Team
Unique ID: glathesis:1992-74715
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 17:01
Last Modified: 27 Sep 2019 17:01

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