Pregnancy outcome in in vitro fertilization (IVF) with repeated cycles

P-226 Different profile and early pregnancy outcome in early and late presentation pattern of ovarian hyperstimulation syndrome. E. G. Papanikolaou, H. Tournaye, W. Verpoest, M. Camus, P. Devroey. Dutch speaking, Free University of Brussels, Brussels, Belgium. OBJECTIVE: to report on a large number of OHSS cases in a single center, with respect to presentation pattern and its association with pregnancy incidence and early pregnancy outcome. In addition, to further distinguish several parameters of the cycle’s events preceded the occurrence of hyperstimulation syndrome. DESIGN: observational study MATERIALS AND METHODS: 118 consecutive patients were included in the study, who have been hospitalised for OHSS after IVF/ICSI treatment between 2000 and 2002. Classification of OHSS, as Early or Late, was performed according to the day of oocyte retrieval. OHSS occurrence within 9 days after OPU was addressed as Early OHSS and the one that occurred after 10 days was classified as Late OHSS. Hospital admission was considered in each case of moderate or severe OHSS. Ovarian stimulation was achieved by either the use of GnRH-Agonist (long/short protocol) or GnRHAntagonist protocol. A clinical pregnancy was defined as the ultrasound observation of fetal cardiac activity after 7 weeks of gestation. Pregnancy losses before this period were assigned as preclinical miscarriages. Fisher’s exact test was used to analyse nominal variables in the form of frequency tables. Normally distributed metric variables were tested with the T-test for independent samples, while non-normally distributed metric variables were analysed with the Mann-Whitney U test. RESULTS: Early OHSS occurred in 57 patients, and Late OHSS complicated 61 patients. 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (p⬍0.05). Although in the early group there was initially a 50% positive HCG rate per embryotransfer, the clinical pregnancy rate was declined to 29,8% due to an increased preclinical pregnancy loss rate, which was significantly higher than the late group (29.2% vs. 5%, p⫽0.01). The ongoing pregnancy rate per cycle was 28.2% in the early and 86.8% in the late group. Multiple pregnancy rates were high in both groups (35.3% and 42.9%, respectively). Estradiol levels and number of follicles on day of HCG were significantly higher in the early OHSS. However, if a threshold of 3000 ng/L of E2 on the day of HCG had been used, only 43.2% of the total cases of OHSS. In addition, number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS, instead of the estradiol values (90% of the severe cases had 14 or more follicles of a diameter ⱖ 11mm, whereas only 44% of them had an estradiol valueⱖ3000 ng/L). CONCLUSION: Our results confirm previous conclusions by other authors that OHSS presents as two distinct clinical entities, depending on the timing of the onset. The early OHSS pattern is related to the exogenous administered HCG and to a higher risk for preclinical miscarriage, whereas late OHSS results from an implanting pregnancy HCG and is more likely to be severe. Our observations suggest that considering high E2 levels as a risk factor is unreliable for the prediction of OHSS. In fact the number of follicles present on the day of HCG administration could be an excellent way of differentiating the patients at high risk of developing either early or late OHSS and especially the severe cases. Further clarification of these two different clinical entities could have implications on research protocols as well as on preventive and management strategies for ovarian hyperstimulation syndrome. Supported by: This study has been supported by grant from the Vrije Universiteit Brussel

IVF and single women undergoing treatment. About two thirds of the data was used to train the network and the rest was used to test the ability of the trained network to predict the success of the treatment. A feed forward network with three layers was used. The back propagation algorithm was used to optimise the connection weights. Several models were developed. The identification of the significant variables was done in a step-wise manner. Initially the models had as many variables as possible. The variables were ranked based on their rank-correlation with the outcome. These were removed one by one and their impact was analysed by observing the reduction in the success of predictions. Variables that significantly reduced the success of prediction upon removal from the model were considered as significant and retained in the model. RESULTS: Based on the analysis, the significant variables were found to be age, duration of infertility, previous IVF live births, presence of fibroid in the uterus, total dosage of drugs, the number of eggs collected, the ratio of number of eggs fertilised to number of eggs collected, and the number of embryos cryo-preserved. The overall success of prediction during the training phase was 73–76 % and 67– 68% in the test phase. Out of this, successful IVF treatments were predicted in 76 –90 % and 44 –78% during the training and test phases. A second random selection of cases for training and test resulted in overall success of prediction of 76 –90% and 55–58% during the training and test phases. Out of these, successful IVF treatments were predicted 88 –96% and 67% during training and test phases respectively. Attempts to train the net using pre-treatment data were not successful. CONCLUSION: A neural network model has been developed that can predict the outcomes of IVF treatment with reasonable success. The model was developed using a small data base and its performance could be improved with more input data. We believe such models are of great potential value to clinics offering treatments and to regulating bodies to formulate the policies. Supported by: None

P-228 Pregnancy outcome in in vitro fertilization (IVF) with repeated cycles. T. Silberstein, J. R. Trimarchi, D. L. Keefe, A. Blazar. Women and Infants’ Hospital, Providence, RI. OBJECTIVE: To evaluate pregnancy rate (PR) and implantation rate (IR) following repeated failed cycles of IVF. DESIGN: Retrospective analysis. MATERIALS AND METHODS: We studied 1177 patients who had 1788 fresh non-donor non-PGD cycles from January, 2001 to December, 2003 that underwent embryo transfer. Patients who achieved pregnancy and returned for a subsequent cycle during the study period were excluded. Cycles were stratified by IVF cycle attempt, further analyzed by patient age, and PR and IR calculated. RESULTS: PR and IR were highest in cycle 1, significantly declined in cycle 2, and plateau for cycles 3–5 at a rate significantly lower than cycle 2. When stratified by age, patients under 38 years old exhibited the same pattern. The probability of pregnancy after 2 failed IVF cycles remained constant at approximately 20% independent of the number of additional cycles. In patients older than 38 years of age the PR and IR in cycles 1 and 2 were significantly lower than younger patients, however there was no decline in PR or IR with advancing IVF attempts. The PR and IR from cycle 1 of older patients corresponded to the PR and IR plateau reach by younger patients at cycle 3 suggesting that older patients are at the plateau of a ⬃20% probability for pregnancy from the start of IVF treatment.

P-227 Prediction of success in IVF treatments using neural networks. G. Venkat, R. Al-Nasser, S. Jerkovic, I. Craft. London Fertility Centre, London, United Kingdom. OBJECTIVE: The aim was to predict the success rate in IVF treatments. DESIGN: All data likely to influence the outcome of IVF treatments were collected and analysed using neural networks. MATERIALS AND METHODS: There were 243 cycles of IVF treatments in 2002 at London Fertility Centre. Of these, 185 cycles were chosen for analysis after excluding cases with failure of fertilisation, natural cycle

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CONCLUSION: Our data concur with that of previous studies suggesting the ICSI operator and the sperm source are important factors in fertilization. Interestingly, the use of antagonist for the stimulation may be a previously unidentified independent predictor of fertilization. This specific finding requires further investigation. The lack of improved pregnancy outcome with antagonist has been attributed to the affect of the antagonist on the endometrium. Our data would support more investigation into the laboratory impact of antagonist protocols. Supported by: None

P-230 CONCLUSION: A significant decline in PR and IR was observed when repeated cycles were needed to achieve pregnancy, however, after cycle 2 a plateau is reached at approximately 20% pregnancy probability. The initial and subsequent cycles of older patients appear to be at this plateau. Supported by: None P-229 Determinates of fertilization rate in ICSI: The stimulation protocol may be an independent predictor. M. P. Rosen, S. Shen, A. T. Dobson, V. Y. Fujimoto, M. I. Cedars, T. L. Telles. University of California San Francisco, San Francisco, CA. OBJECTIVE: ICSI was initially utilized to overcome fertilization failure. Despite the prevalent use of ICSI, the fertilization rate remains around 50–70%, which appears to be no different than standard IVF with non-male factor. This suggests that factors other than sperm binding and penetration may limit the fertilization rate. While some investigators have demonstrated that the sperm source or the ICSI operator and technique are factors important to fertilization, others believe the etiology is secondary to reduced activation of the egg. The aim of the current study was to identify potential predictors of fertilization in our ICSI population while controlling for multiple variables. DESIGN: Prospective Study. MATERIALS AND METHODS: First attempts of IVF at the UCSF IVF program from 2002 to 2003 were evaluated (563 cycles) Multivariate analyses were performed using the generalized linear model routines in Stata, Ver 7.0 (Stata Corporation, College Station, TX) to perform logistic regression allowing for clustering by cycle. The models were determined by backward elimination in a guided fashion, starting with a model including all the predictors (ICSI operator, sperm source, stimulation protocol, age, day 3 FSH, E2 on day of HCG, number of mature oocytes retrieved); then eliminating those that were not statistically significant one at a time guided by the previous literature and clinical experience. Tests were declared statistically significant for a two-sided p-value ⬍ 0.05. To further the study, a second analysis was performed after excluding for poor prognosis patients (female age ⬎ 38 years and FSH ⬎ 10 MIU). RESULTS: The original model illustrated that the ICSI operator, stimulation protocol and sperm source were significantly associated with fertilization rate. More specifically, the micro-dose flare protocol and antagonist protocol resulted in lower fertilization rates, as did cycles in which sperm was retrieved from testicular biopsies (TESA, TESE) and frozen MESA. After excluding for poor prognosis patients, the antagonist protocol still negatively impacts the fertilization rate. The results from this second analysis are listed in the following table:

Embryo morphology score is predictive of day 3 implantation and pregnancy rates. S. J. Dennis, M. A. Thomas, D. B. Williams, J. C. Robins. University of Cincinnati Medical Center, Cincinnati, OH. OBJECTIVE: To determine if embryo cleavage state or embryo morphology on day three after oocyte retrieval correlates with implantation or pregnancy rates. DESIGN: A historical cohort study evaluating all fresh embryo transfers performed between January 2003 and December 2003 at the University of Cincinnati Center for Reproductive Health. MATERIALS AND METHODS: Patients undergoing fresh day three embryo transfers were grouped by mean cleavage state and mean morphology as determined immediately prior to transfer. Cleavage state groups were defined as: fewer than 6 cells, 6 –7 cells and 8 or more cells. Morphology was graded as described by Veeck. Five morphology groups were defined as mean grades: 1, 1.1–2, 2.1–3, and 3.1– 4. Data recorded included patient demographic information, the number of embryos transferred and the pregnancy outcome. Statistics were analyzed using ANOVA for continuous variables and chi square for proportional data. Correlation analysis was performed using Spearman’s correlation. RESULTS: There were 85 fresh ETs performed during the study period. The overall implantation rate was 29.6% and pregnancy rate was 36.4%. The average number of embryos transferred was 2.7. As anticipated, there was a significant correlation between the number of embryos transferred and both implantation and pregnancy rates (p⬍0.05). When analyzed in groups (both by cleavage state and morphology) there was no significant difference in the average age, gravidity or parity. The cleavage state was not predictive of outcome. However, morphologic grade was highly predictive of both implantation rate (r2⫽0.07, p⫽0.01) and pregnancy rate (r2⫽0.06, p⫽0.02). Implantation and pregnancy rates, by group, are illustrated in the figure below.

CONCLUSION: The goal of an ART program is to deliver high pregnancy rates with minimal multiple gestations. This study demonstrates that embryo grade is highly predictive of implantation and pregnancy. Therefore, this parameter may be used to determine the number of embryos to transfer. Surprisingly, cleavage state was not predictive of outcome, which may be due to the small number of embryos transferred with less than 6 cells. Supported by: None

P-231 Comparison of the first three cycles of in vitro fertilization (IVF): Are success rates different for women using IVF in subsequent cycles? G.

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Vol. 82, Suppl. 2, September 2004