High responders are not exempt from detrimental effects of prematurely rising progesterone levels in fresh embryo transfer cycles

Research question

Are high-responder IVF patients protected from the deleterious effect of prematurely elevated serum progesterone level on the probability of pregnancy?

Design

In this retrospective cohort study, 2971 autologous fresh embryo transfer IVF cycles with gonadotrophin-releasing hormone agonist long protocol were analysed to investigate whether the detrimental effect of prematurely rising progesterone levels on clinical pregnancy rate (CPR) varies depending on the magnitude of ovarian response. Nine different evenly spaced intervals were constructed for serum progesterone level on the human chorionic gonadotrophin day (<0.5/0.5–0.9/1–1.4/1.5–1.9/2–2.4/2.5–2.9/3–3.4/3.5–3.9/>4 ng/ml). Then, IVF cycles in each of these intervals were further divided into low (≤3 oocytes), normal (4–15 oocytes) and high responders (≥16 oocytes).

Results

The progressive rise of serum progesterone from the <0.5 to the >4 ng/ml interval caused a gradual and continuous decline in the CPR of all three types of ovarian response. The absolute difference in the CPR between the lowest and the highest progesterone groups was not related to the magnitude of ovarian response (–26.6%, –37.7% and –40.7% for the low, normal and high responders, respectively). On multivariate logistic regression analysis, the detrimental effect of progesterone started at 1.5–1.9 ng/ml, 3.0–3.4 ng/ml and 4.0–4.4 ng/ml intervals for the low, normal and high responders, respectively.

Conclusion

High responders are not exempt from the detrimental effects of prematurely rising serum progesterone levels but the threshold interval where the detrimental effect begins is higher in the high responders compared with the low and normal responders.