Effect of elevated progesterone on day of trigger on live birth with a day 5 versus day 6 blastocyst transfer

FERTILITY AND STERILITY(2016)

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Abstract
Recent literature demonstrates a negative effect of elevated progesterone (P) on day of oocyte maturation trigger causing endometrial-embryo asynchrony, ultimately leading to decreased live birth rates. In fresh blastocyst transfers, this effect may be more pronounced in day 6 compared to day 5 embryo transfers (ET), as embryo growth would be slower while endometrial development more advanced. Our objective was to evaluate the effect of P on the day of trigger in fresh IVF transfer cycles on day 5 versus day 6. Retrospective cohort study. Autologous IVF cycles with fresh ET on day 5 and day 6 from 2011-2014 were included if P was measured on the day of trigger. The primary outcome was live birth. GEE modeling was performed to control for confounders including embryo quality, stage, age, and number of embryos transferred and account for multiple cycles. GEE modeling was used to determine the effect of P on day 5 versus day 6 ET comparing P as a continuous variable and P as a threshold variable ≥ 1.5ng/mL. ROC curves were evaluated for P and live birth. 4,120 day 5 ETs and 230 day 6 ETs were analyzed. Day 6 transfers were less likely to have good quality embryos than day 5 (73% vs 83%) but both cohorts had similar rates of blastocyst stage ET (92% vs 91%). Live birth was less likely in day 6 embryo transfers (34% vs 46%) even when controlling for embryo confounders. In adjusted GEE models, the effect of P was more pronounced on day 6 ET than day 5 ET (OR 0.56 vs OR 0.77). Similarly, the effect of P>1.5 ng/ml was more pronounced on day 6 ET than day 5 ET (OR 0.40 vs OR 0.69). Day 6 ET live birth rates were moderately lower when P was in the normal range, but became much lower when P was > 1.5ng/ml (Table 1). The AUC for P predicting live birth was higher in day 6 embryos than day 5 embryos (0.58 vs 0.54). Interaction testing of P on day of ET demonstrated P<0.0001, further suggesting that the effect of P was more pronounced on a day 6 ET.Tabled 1Table 1: The effect of P on live birth among day 5 versus day 6 ET.P<1.5P≥1.5DifferenceP valueDay 547%37%-10%<0.01Day 639%20%-19%<0.01Difference-8%-17%P value0.04<0.01 Open table in a new tab P had a greater effect on day 6 ET compared to day 5. This suggests further endometrial-embryo asynchrony on day 6 and a lower threshold for freezing day 6 blastocysts for frozen ET.
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Key words
elevated progesterone,live birth
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