Midluteal Estradiol-to-Progesterone Ratio(E2/P4)
Has No Effect on IVF Outcome

Authors: 1I Souter, 2D Hill, 3MW Surrey,. 1Dept. of Ob/Gyn, David Geffen School of Medicine at UCLA, Los Angeles, CA 2ART Center and 3Southern California Reproductive Center, Beverly Hills, CA.

Background: Progesterone secretion is considered the major hormonal event during the luteal phase, and estradiol appears to play a crucial role as well. Whether an optimal estradiol-to-progesterone ratio is critical for implantation and progression of early pregnancy remains unclear.

Objective: To determine whether altered midluteal E2/P4 ratios have an effect on embryo implantation and pregnancy maintenance in IVF cycles.

Materials and Methods: We retrospectively evaluated 97 patients undergoing IVF-fresh ET. Serum was obtained 5 days after ET and concentrations of estradiol and progesterone were determined. The ratio of estradiol-to-progesterone was calculated for conception and non-conception cycles. Data are expressed as mean ± SD. Student’s t-test, c2 and Fisher’s exact test were used for statistical analysis.

Results: 97 IVF-ET cycles resulted in 53 pregnancies (54.7%). Fifty-eight day-3, sixteen day-4, and twenty-three day-5 ETs resulted in 29,7, and 17 pregnancies respectively. Clinical pregnancy rates were 41.3%, 43.8%, and 60.9% respectively.

Five days after ET ongoing clinical pregnancies had significantly higher progesterone values compared to spontaneous abortion and non-conception cycles (80.3±56 ng/dL, 64.2±36 ng/dL, and 59.3±31 ng/dL respectively- p:0.0425). This effect was more pronounced five days after day-3 ETs (92.2±62 ng/dL vs 59.6±33.5 ng/dL-p:0.025).

Progesterone concentrations higher than 60 ng/dL were associated with significantly increased pregnancy rates (62.5% vs 34.6%-p:0.035). 5 days after a day-3 ET, higher E2/P4 ratios were noted in unsuccessful cycles compared to clinical pregnancy ones (12.6 vs 8.2, p:0.08).

A trend towards a negative effect on pregnancy rates was noted in all cycles (day-3 to day-5 ETs), when the ratio was >15.0 (PR:30%, p:NS), however these observations did not reach statistical significance. Evaluation of different E2/P4 ratios did not reveal any significant differences in pregnancy and implantation rates between conception and non-conception cycles (Fig.1).

Conclusions: Our data suggests that altered midluteal E2/P4 ratios do not result in reduced implantation and pregnancy rates. However, midluteal progesterone concentration of >60ng/dl is associated with increased endometrial receptivity and successful IVF outcome.

Luteal phase support should be directed towards optimizing progesterone concentration without a goal of altering the balance of estradiol to progesterone, since this is not crucial for implantation and pregnancy maintenance.