Premature progesterone elevation during controlled ovarian stimulation has limited impact on embryologic outcomes.

Objective

To evaluate the impact of elevated progesterone (P4) level on embryology outcomes in patients undergoing in vitro fertilization (IVF).

Design

Retrospective cohort study using propensity-score matched analysis (PSM). SUBJECTS Patients undergoing their first freeze-all cycle between January 2017 and December 2024 at an academic-affiliated center. EXPOSURE Trigger day serum P4 level. MAIN OUTCOME MEASURES Primary outcome was blastulation rate per fertilized zygote (2PN). Secondary outcomes included oocyte maturation, fertilization, and euploidy rates. Outcomes were compared between elevated (≥1.5 ng/mL) versus normal (<1.5 ng/mL) P4 levels, as well as across P4 quartiles. An additional analysis was performed to assess the probability of persistent P4 elevation in a subsequent cycle. Analysis cohort was formed after PSM on oocyte age, partner age, day 3 FSH, sperm type, BMI, AMH, antral follicle count, pituitary suppression protocol, follicle count at trigger, trigger type, and stimulation duration. Multivariable regression analyses doubly adjusting for AMH, FSH, oocyte age, >15mm follicle count, and trigger estradiol (E2) levels were conducted.

Results

16,321 cycles were initially analyzed - 3,749 with trigger day P4 ≥1.5 ng/mL and 12,572 with P4 <1.5 ng/mL. Following PSM, 6,620 cycles (3,310 per group) were analyzed. Despite matching, patients with P4 elevation had higher trigger day E2 (median 3,369 vs. 3,105.5 pg/mL, p<0.001) and follicles >15mm (median 16.0 vs. 15.0, p<0.001). P4 elevation was associated with a small but statistically significant decrease in oocyte maturation rate (67.2 vs 68.5%; adjusted Risk Ratio [aRR] 0.98, 95% CI 0.97-0.98, p<0.001), fertilization rate (82.1 vs. 82.6%; aRR 0.99, 95% CI 0.99-1.00, p=0.018) and blastulation rate per 2PN (67.0 vs 68.3%; aRR 0.98, 95% CI 0.97-0.99, p=0.001), but no difference in euploidy rate. A higher percentage of immature oocytes was noted in the higher P4 quartiles. The probability of P4 elevation in a subsequent cycle was significantly higher for those with a first cycle elevation compared to those with no first cycle elevation (57.5% vs. 14.3%, respectively, p<0.001).

Conclusion

Premature P4 elevation is associated with significant decreases in oocyte maturation, fertilization, and blastulation rates; however, the magnitude of these differences is small and may not be clinically meaningful.