STUDY QUESTION: Is there a relationship between serum progesterone (P) and endometrial volume on the day of embryo transfer (ET) with ongoing pregnancy rate (OPR) in artificial endometrium preparation cycles. SUMMARY ANSWER: Patients with serum P < 9.2 ng/mL on the day of ET had a significantly lower OPR but endometrial volume was not related with OPR. WHAT IS KNOWN ALREADY: A window of optimal serum P levels during the embryo implantation period has been described in artificial endometrium preparation cycles. A very low endometrial volume is related to poor reproductive outcome. STUDY DESIGN, SIZE, DURATION: Prospective cohort study with 244 patients who underwent ET in an oocyte donation cycle after an artificial endometrial preparation cycle with estradiol valerate and vaginal micronized progesterone (400 mg/12 h). The study period went from 22 Feb. 2016 to 25 Oct. 2016 (8 mo). Sample size was calculated to detect a 20% difference in OPR (35-55%) between two groups according to serum P levels in a two-sided test (80% statistical power, 95% confidence interval (CI)). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing their first/s oocyte donation cycle, aged < 50, BMI < 30 kg/m2, triple layer endometrium >6.5 mm and 1-2 good quality transferred blastocysts. A private infertility center. Serum P determination and 3D ultrasound of uterine cavity were performed on the day of ET. Endometrial volume measurements were taken using a virtual organ computer-aided anal. (VOCALTM) system. The primary endpoint was OPR beyond pregnancy week 12. MAIN RESULTS AND ROLE OF CHANCE: About 211 of the 244 recruited patients fulfilled all the inclusion/exclusion criteria. Mean serum P on the day of embryo transfer was 12.7 ± 5.4 ng/mL (Centiles 25, 9.2; 50, 11.8; 75, 15.8). OPRs according to serum P quartiles were: Q1: 32.7%; Q2: 49.1%; Q3: 58.5%; Q4: 50.9%. The OPR of Q1 was significantly lower than Q2-Q4: 32.7% vs. 52.8%; P = 0.016; RR (95% CI): 0.62 (0.41-0.94). The mean endometrial volume was 3.4 ± 1.9 mL. Serum P on the day of ET did not correlate with endometrial volume A logistic regression anal., adjusted for all the potential confounders, showed that OPR significantly lowered between women with serum P < 9.2 ng/mL vs. ≥9.2 ng/mL (OR: 0.297; 95%CI: 0.113-0.779); P = 0.013. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.59 (0.51-0.67). LIMITATIONS, REASONS FOR CAUTION: Only the women with normal uterine cavity, appropriate endometrial thickness and good quality blastocysts transfer were included. Extrapolation to an unselected population or to other routes and/or doses of administering P needs to be validated. The role of endometrial volume could not be fully defined as very few patients presented a very low volume WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests a min. threshold of serum P values on the day of ET that needs to be reached in artificial endometrial preparation cycles to optimize outcome. No upper threshold could be defined.