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Title

Levels of estradiol and progesterone in the middle luteal phase (Day 6 after transfer) and correlation with ongoing and live birth rates with transfer of thawed blastocysts in artificial cycles

Objective

In recent years, there has been a growing interest in progesterone (P4) levels measured on the day of embryo transfer or 1 day before in artificial cycles, as there could be a cutoff point in P4 levels above which the chances of pregnancy increase. Few studies have measured P4 levels early, specifically on Day 6 after blastocyst transfer (DT6) and correlation with ongoing or live birth rates (ONG/LBR). In this study, we evaluated pregnancy chances in relation to estradiol (E2) and P4 levels measured on DT6 of viable blastocysts in cycles without the presence of corpora lutea (artificial cycles).

Methods

Patients from a private clinic who underwent frozen embryo transfer (FET) between January 2017 and December 2021, using artificial cycles (6mg/day E2 valerate and occasionally adding transdermal gel in the endometrial proliferative phase, and 600mg/day vaginal or 50mg/day intramuscular micronized P4), that were followed by the author. E2, P4, and beta-hCG levels were measured on DT6 (transfer day, Day 0). In this period 227 transfers were performed by the author. Of these,73 cycles were excluded for different reasons, remaining 154, which met all the criteria.
We evaluated the cutoff point on DT6 for these two hormones using the ROC curve and area under the curve (AUC) to determine a threshold for assessing ONG/LBR above and below the cutoff point, determined by sensitivity and specificity. We also assessed ONG/LBR by range of progesterone levels.
Furthermore, we compared the mean P4 levels between the vaginal and intramuscular groups and their ONG/LBR.

Results

The ROC curve for E2 showed the highest sensitivity/specificity for ONG/LBR with a dosage of 158.5 pg/ml and a range of 49.8 to 1149 pg/ml and odds bellow and above 158.5 pg/ml were 21,43% and 36,51% respectively, and p=0.1843. Then, we had a curve flattened with an AUC of 0.5169, p=0.7334. The ROC curve for P4 showed the highest sensitivity/specificity with 9.6 ng/ml and a range of 3.9 to 47 ng/ml, with an AUC of 0.5901, p=0.0678. The pregnancy rates for ONG/LBR below and above the 9.6 cutoff point were 50% and 25,9% and OR 0.3506 (0.1771 - 0.7132), p= 0,0038. The odds for ONG/LBR by P4 bands were A – 3.9 to 7 ng/ml (41,1%), B – 7.1 to 10 ng/ml (50%), C – 10.1 to 20 ng/ml (25%) and D - > 20 ng/ml (29,7%). The p values were p.a/b= 0.5742, p.b/c= 0.0170 and p.c/d= 0.6452 (table 1).
The mean P4 dosage was 12.7 ng/ml for vaginal and 22.2 ng/ml for intramuscular use, with pregnancy chances for ONG/LBR at 37,1% in the vaginal group and 26,5% in the intramuscular group, OR 0.6111 (0.2967 – 1.291), p=0.2070.

Conclusion

Our data show no predictive value for pregnancy ONG/LBR with E2 dosage and low prognostic capacity for pregnancy ONG/LBR with P4 measurements. Determining a cutoff showed no utility for E2, and the P4 showed higher chances of ONG/LBR below 9,6 ng/ml. The mean P4 dosages with vaginal or intramuscular use were different as expected, but ONG/LBR were similar.

Keywords

progesterone, artificial cycles, ongoing, estradiol, embryo transfer

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