Clinical aspects of embryo implantation : from the perspective of tissue perfusion
Hypothesis: Pelvic perfusion is the pivotal factor for the outcome of in vitro fertilisation (IVF) treatment once clinical and embryological variables are controlled for their effect.;Demonstration of Hypothesis: In a series of three studies, the clinical aspects of embryo implantation were examined from the perspective of tissue perfusion.;Epidemiological Study: Clinical and embryological data were evaluated to predict multiplicity of implantation and ongoing pregnancy in IVF treatment. Oocyte and embryo quality were appraised and the impact of the number of embryos transferred was assessed.;Study on In-vivo Vascular Physiology: The prognostic role of utero-ovarian perfusion and its pharmacological manipulation with low dose aspirin was evaluated in the outcome of IVF treatment. Serum, follicular fluid vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) concentrations were correlated with Doppler indices.;Study on In-vivo Endometrial Physiology: Endometrial receptivity (in terms of endometrial thickness and echo-pattern) and VEGF-VEGFR concentrations were evaluated with regards to the outcome of frozen-thawed embryo replacement (FTER) during natural and hormone replacement cycles.;Results: The epidemiological study showed that the outcome of IVF treatment was closely associated with the severity of subfertility. Ovarian reserve and response to stimulation were the key factors. The probability of pregnancy was affected by the number and quality of oocytes and by their fertilisation rate and the cleavage rate of the resulting embryos. The potential to provide mature oocytes and high quality embryos was an inherent characteristic of the ovaries and independent of stimulation protocols. When embryo quality was taken into consideration, the number of embryos transferred no longer affected the chance of pregnancy. The clinical study showed that the chance of pregnancy was directly dependant upon tissue perfusion. Pregnancy rates were very low with uterine artery pulsatility index >3 (PI) and peri-follicular PI >1. Better ovarian reserve, response to stimulation, endometrial development, implantation and pregnancy rates were associated with low follicular fluid VEGF-VEGFR levels and this was also associated with good uterine and endometrial perfusion. Aspirin (150 mg/day) had no beneficial effect on Doppler indices, ovarian response to stimulation, implantation or pregnancy rates. Pregnancy rates were similar with naturally and hormonally prepared endometrium in frozen-thawed embryo replacement cycles. Higher serum VEGF and lower VEGFR levels were observed in pregnant cycles, but the differences were not significant. Endometrial echo-pattern and thickness did not affect conception.;Conclusions: Tissue perfusion plays a key role in the physiological steps leading to conception and implantation. Aspirin (150 mg/day) improved neither tissue perfusion nor the outcome of fresh embryo transfer. The type of endometrial preparation did not affect the outcome of frozen-thawed embryo replacement cycles.