Are extremely high progesterone levels still an issue in IVF?

Background: Premature luteinization of one or more developing follicles complicates 1–2 % of controlled ovarian stimulation cycles for assisted reproduction. The management of this complication is controversial, with cycle cancellation likely representing the most commonly used strategy. The aim of this study was to evaluate the efficacy of the “freeze-all” policy—where the entire cohort of blastocysts is cryopreserved for subsequent frozen-thawed embryo transfer—in treating cases of premature luteinization. Methods: Patients experiencing premature luteinization during controlled ovarian stimulation—identified by extremely high progesterone levels at induction (P levels ≥3.0 ng/ml and/or P/estradiol ratio ≥1, n = 42)—were included in a “freeze-all” program and compared to controls undergoing a “freeze-all” program with normal progesterone levels at induction (P < 1.5 ng/ml, n = 67). Results: Blastulation rate was comparable between patients with premature luteinization and controls (48.1 ± 20.5 % in Cases vs. 52.3 ± 24.9 % in Controls, p = 0.36). Ongoing pregnancy rates after the first frozen-thawed embryo transfer (38.1 % in Cases and 41.0 % in Controls, p = 0.83) and cumulative ongoing pregnancy rates after three frozen-thawed embryo transfer cycles (40.5 % in Cases vs. 47.8 % in Controls, p = 0.55) were also similar. Conclusions: These results show that extremely marked progesterone elevation throughout controlled ovarian stimulation does not impair blastocyst development and implantation potential in the context of a “freeze-all” strategy. Based on this, adoption of the “freeze-all” strategy represents a valuable tool in treating premature luteinization. In contrast, cycle cancellation—likely the most frequently used method for management of this complication—currently represents a misconduct.