Evidence of interplay between plasma endothelin-1 and 17 beta-estradiol in regulation of uterine blood flow and endometrial growth in infertile women.

Objective: To determine the effects of gonadotropin-induced ovarian stimulation on the plasma levels of endothelin-1 as well as on uterine blood flow and endometrial thickness.

Design: Controlled cross-over clinical study.

Setting: Academic research environment.

Patient(s): Eighteen volunteer infertile women (31.4 +/- 2.5 years, mean +/- SE) participating in an IVF-ET program.

Intervention(s): Transvaginal Doppler ultrasound was performed and blood samples were collected 4 days after the LH surge in a spontaneous cycle and 4 days after hCG administration in a subsequent gonadotropin-stimulated cycle.

Main Outcome Measure(s): Plasma levels of E2, P, and endothelin-1; uterine artery pulsatility index; and endometrial thickness.

Result(s): Stimulated cycles were associated with significantly higher E2 levels (101.0 +/- 10.2 versus 723.5 +/- 57.3 pg/mL [conversion Factor to SI unit, 3.671]; spontaneous versus stimulated), thicker endometrium (9.2 +/- 2.5 versus 11.4 +/- 2.9 mm), and lower endothelin-1 levels (2.5 +/- 0.1 versus 2.1 +/- 0.1 pg/mL [conversion factor to SI unit, 0.4]) and pulsatility index (3.22 +/- 0.12 versus 2.63 +/- 0.08) than spontaneous cycles. Endothelin-1 correlated negatively with E2 (r = -0.38), but not with P or pulsatility index. Differences in endothelin-1 and endometrial thickness between spontaneous and stimulated cycles correlated negatively (r = -0.56) with each other.

Conclusion: Our results suggest an inhibitory role for E2 in the release of endothelin-1, which could be a factor in the regulation of uterine and endometrial blood flow.