| Summary: | The overall purpose of this thesis was to identify factors which influence the outcome of IVF treatment and which might be amenable to modification in order to improve pregnancy rates following this form of treatment. To this end I performed a historical review of the advances that have been made in reproductive treatment since before the birth of Louise Brown in 1978, and a retrospective analysis of the result of a single IVF unit over a 6 year period from 1999 to 2005. This identified a number of factors on which IVF pregnancy rates depend. I found that there is a decrease in the pregnancy and implantation rates and an increase in the abortion rates with a consequent decrease in the live birth rate with an increase in the female age. The data demonstrated that the pregnancy, implantation, abortion, and live birth rates for female age 20-25 years was 42%, 21.95%, 37.5%, and 26.3% respectively. For the age of 26-30 years the comparative figures were 44.5%, 27.4%,12.34%, and 39%, for the age of 31-35 years 35.7%, 22%,16%, and 29.9%, for the age of 36-39 years 27%, 13.9%, 22.7%, and 20.5% and for patients who were 40 years and above 17%, 7.4%, 27.3%, and 12.9%. (P<0.05) for the pregnancy, implantation, and live birth rates, (P>0.05) for the abortion rate. In addition, I found that there is a decrease in the pregnancy rate with increasing age of the male partner although this did not reach a statistically significant level. For male patients whose age was between 20-30 years the pregnancy rate was 42.7% compared with 37.8% if they were between 31-44 years and 31.6% if they were 45 years or above (P >0.05). I found that the outcome of IVF-ET is affected by the number of embryos transferred, and whether the embryos are fresh or cryopreserved. The data showed that the pregnancy and implantation rates for single embryo transfer were 16.9%; for double embryo transfer were 37.3% and 23.22% respectively, and for triple embryo transfer 27.12% and 11.64% respectively. In addition, I found that the difference in the twin and triplet rates were 0% and 0% respectively for single embryo transfer, 24.5 and 0.02% respectively for double embryo transfer, and 26.8% and 1.5% respectively for triple embryo transfer. The differences in pregnancy and implantation rates between the transfer of two fresh and two frozen embryos were 37.3% versus 27.3% (P>0.05) and 23.22% versus 16.36% (P>0.05). The outcome of IVF-ET was also found to be affected by the grade and cleaving rate of embryos. The differences in the pregnancy and implantation rates between the transfer of high-grade and low grade embryos were 61.4% versus 11.5%, and 35.8% versus 6.96% (P<0.0001). The differences in the pregnancy and implantation rates after the transfer of slowly cleaving embryos or rapidly cleaving embryos transferred on day 2 was 18.3% versus 44% respectively (P<0.0001),and 11% versus 28% respectively (P<0.0001).Similar differences were seen between slowly or rapidly cleaving embryos transferred on day 3. The difference were 20% versus 63.4% respectively (P<0.017) for the pregnancy rate, and 13.3% versus 40.14% respectively (P <0.027) for the implantation rate. The day of embryo transfer was also relevant, with a better outcome when the embryos were transferred on day three rather than day two. The differences were 42.8% versus 35.1% (P<0.024) for the pregnancy rate and 27.43% versus 21.53% (P<0.005) for the implantation rate. Transcervical embryo transfer (TCET) was more likely than transmyometrial embryo transfer (TMET) to lead to pregnancy, whether the transfer was easy or difficult. The outcome of TMET was low even if it was easy. Zygote intrafallopian transfer (ZIFT) is preferred to TMET if at least one fallopian tube is patent. The outcome differs when different operators perform ET and the difference in the pregnancy rate for three different operators was found to vary between 35.2%, 41.2%, and 26.5% (P<0.026). The outcomes were good if nurses performed the procedure, and a new trainee was found to need around one year to become expert in the technique with pregnancy rates increasing from 34.54% to 47.3% at the end of one year of performing the procedures. I found also that the outcome was affected by the cause of infertility, with better outcomes when the aetiology was tubal, unexplained, or polycystic ovary syndrome (PCOS), and poorer outcomes when the aetiology was endometriosis, untreated hydrosalpinges or after a history of ectopic pregnancy. Differences in pregnancy rate according to aetiology varied between 61.9% and 11.8% (P <0.0001). By studying the results of the egg-sharing programme, I was able to show that aging of the ovary is more important than aging of the uterus and the outcome of IVF/ET in egg recipients is almost the same as the outcome in egg sharing donors. The pregnancy and implantation rates were 35.5%, and 18.33% respectively for egg recipients, and 35.5%, and 18.06% respectively for egg sharing donors. In addition, I found that abortion rates were higher and consequently live birth rates were considerably lower in the egg recipients as compared to the egg-sharing patients, abortion rates 26.19% versus 9%, P>0.05, live birth rates 26.5% versus 32.25%, P>0.05. Finally, I found that abortion rates were higher and consequently live birth rates were lower with increasing age of recipient. The abortion and live birth rates according to the recipient age were 18.75%, 30.95% respectively for recipients less than 35 years, 28.57%,26.31% respectively for those 36-39 years and 31.56%, 23.21% respectively for those 40 years and above, P>0.05. In addition, I found that the outcome is better when egg recipient patients have ovarian function as compared with egg recipient patients with no ovarian function, and the pregnancy rate was 41.3% for the first group and 29.62% for the second group, P>0.05. Egg sharing patients were found to have lower pregnancy and implantation rates while the live birth rate of egg sharing is virtually the same as standard IVF patients. The difference in the pregnancy, implantation, abortion, and live birth rates between the two groups was (35.52% versus 40.7%), (18.3% versus 25.61%), (9% versus 20.46%), and (32.25% versus 32.29%). Hence, egg sharing has no detrimental effect on the outcome for egg sharing patients. The only factor amenable to modification for each and every couple was identified as the technique of embryo transfer. Hence, I undertook a literature search to identify the effects of the technique that might be relevant. I also used time-lapsed ultrasound video imaging of the uterus as a means of identifying those cycles that might have a favourable or unfavourable outcome as a result of a good or poor ET technique. My results show that exaggerated junctional zone contractions do indeed have a detrimental effect on the outcome of IVF-ET our data shows that the pregnancy rate for those who had less than 5 uterine contractions per 2 minutes as compared to the pregnancy rate for patients who had more than 5 uterine contractions per 2 minutes was 29.7% versus 0% respectively p=0.026, but an easy embryo transfer did not appear to change the character or the frequency of junctional zone contractions.
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