The effect of progesterone administration in the follicular phase of an artificial cycle on endometrial morphology: a model of premature luteinization.

OBJECTIVE

To evaluate the effect of premature P administration on artificially prepared endometrium in women with ovarian failure.

DESIGN

To mimic premature luteinization, patients with ovarian failure were treated with continuous estrogen and episodic P during the follicular phase of artificial cycles.

SETTING

In vitro fertilization unit at a university hospital.

PATIENTS

The study group included 16 patients with ovarian failure who were randomly divided into two groups. Group A (8 patients) was treated by episodic P administration during the artificial follicular phase on days 2 and 7 (12.5 mg of P in oil IM), and in group B (8 patients), P (6.25 mg) was added on days 3, 4, and 5. Another 16 patients (group C), age matched to the study group, were arbitrarily allocated to serve as controls and had standard preparatory cycles without P supplementation in the follicular phase. Serum E2 and P levels and endometrial biopsies were taken on days 14 and 26.

RESULTS

Serum E2 levels were comparable between the study group (group A+B) and controls on both days 14 and 26. Although serum P levels did not differ between the groups on day 26, it was higher in the follicular phase of the study group than in the controls (1.9 +/- 4.0 and 0.2 +/- 0.1 ng/mL, respectively). In the study group, 8 of 16 patients demonstrated early secretory changes in the late follicular phase biopsies, and 9 of 16 women developed stromal-glandular discrepancy in the late luteal phase. This differed significantly from the controls in which only one late luteal biopsy was out of phase.

CONCLUSIONS

Episodic surges of P during the follicular phase may result in impaired endometrial development that cannot be corrected by P supplementation during the luteal phase. This unique model provides evidence for the potential detrimental effect of premature P secretion in the follicular phase on endometrial function.