Early follicular rise of serum progesterone concentration in response to a flare-up effect of gonadotrophin-releasing hormone agonist impairs follicular recruitment for in-vitro fertilization.

A retrospective study of 150 cycles of in-vitro fertilization (IVF) was undertaken to determine the impact of elevated serum progesterone in the early follicular phase of IVF cycles utilizing gonadotrophin-releasing hormone agonist (GnRHa) initiated in the follicular phase. A total of 127 patients identified as being at risk for poor response to stimulation were treated with a flare-up protocol of GnRHa combined with high dose follicle stimulating hormone (FSH). Patients were excluded for severe male factor requiring micromanipulation. Patients were stimulated with GnRHa beginning on cycle day 2, and high dose FSH beginning on cycle day 3. Some 85% of the cycles exhibited a rise of serum progesterone to a peak concentration of > 1.0 ng/ml (range, 1.2-4.2 ng/ml) during cycle days 2-6. When compared to cycles with no demonstrable progesterone rise, cycles with a rise were associated with a significantly decreased ovarian response: more ampoules of gonadotrophin were required (mean 26.8 versus 22.6, P < 0.05), lower peak oestradiol concentration was reached (mean 774 pg/ml versus 1030; P < 0.05), and fewer mature oocytes were harvested (mean 4.6 versus 7.5; P < 0.01). Among the different pregnancy outcomes (clinical pregnancy, no pregnancy, ongoing pregnancy, and miscarriage), there were no significant differences detected in the early follicular progesterone concentrations as measured by peak progesterone, progesterone area under the curve (days 2-6), and day of peak progesterone. The follicular phase initiation of GnRHa can result in significant elevations of serum progesterone in the early follicular phase, which may impair follicular recruitment and overall ovarian response.