Transvaginal progesterone supplementation increases serum insulin-like growth factor-binding protein-1 levels

The objective of this study was to assess the effect, which might be mediated by progesterone-dependent insulin-like growth factor-binding protein-1 (IGFBP-1), of micronized progesterone supplementation through different administration routes (oral or vaginal) on successful pregnancy. A total of 299 anovulatory women were treated with clomiphene citrate (100 mg/day on days 5-9 of the menstrual cycle) to stimulate follicular growth. Human chorionic gonadotropin (hCG, 10,000 IU) was injected intramuscularly when at least one follicle was > 20 mm in diameter as monitored by transvaginal ultrasonography. Micronized progesterone (300 mg/day, at bedtime) was used as supplementation of progesterone randomly by oral (n = 153) or vaginal (n = 146) administration from approximately 36-48 h after hCG administration until the following menstrual period or the 10th week of gestation from the last menstrual period. As a control, 18 apparently healthy females with at least three regular menstrual cycles immediately before the present study were also recruited but no interventions were made. Serum levels of progesterone, IGFBP-1, insulin-like growth factor-I (IGF-I) and insulin were determined on day 8 after hCG administration (day 0 indicates the day of hCG administration; progesterone supplementation group) or on day 21 of the menstrual cycle (controls). In the midluteal phase higher progesterone and lower IGFBP-1 levels were observed in the serum from patients supplemented with oral progesterone than in those using vaginal progesterone. Total and continuing pregnancy rates were also higher in the patients using oral than in those using vaginal progesterone (p < 0.04, by the zI-test). However, there was no difference in serum IGF-I or insulin level between the groups. It was concluded that oral administration of micronized progesterone at bedtime appears to be a convenient method of luteal supplement, whereas vaginal supplementation during the luteal phase might directly stimulate endometrial production of IGFBP-1, which possibly, in turn, deters embryo implantation and results in a decrease in the pregnancy rate.