Priming with gonadotropin-releasing hormone restores gonadotropin secretion during first but not second trimester of pregnancy.

This study was designed to determine whether the lack of secretion of endogenous gonadotropin-releasing hormone is the etiology of the hypogonadotropic state of pregnancy. For this purpose, five pregnant women in their first trimester received a single intravenous dose of 150 micrograms of gonadotropin-releasing hormone. Another five women in the first trimester and five women in the second trimester of pregnancy received daily intramuscular injections of 500 micrograms of gonadotropin-releasing hormone for 10 consecutive days. This was followed by a single 150 micrograms gonadotropin-releasing hormone test and then a 24-hour pulsatile infusion of gonadotropin-releasing hormone of 10 micrograms/min/6 min given every hour. Baseline plasma beta-luteinizing hormone and follicle-stimulating hormone were undetectable in all women. Mean +/- SEM plasma beta-human chorionic gonadotropin was significantly higher (p less than 0.001) in the first trimester than in the second trimester, and mean plasma estradiol and prolactin were significantly increased (p less than 0.001 and 0.05, respectively) during the second trimester of pregnancy. After the 10-day treatment with gonadotropin-releasing hormone there was a significant increase (p less than 0.05) in baseline beta-luteinizing hormone and follicle-stimulating hormone only in the first-trimester pregnant women. The single as well as the pulsatile administration of gonadotropin-releasing hormone resulted in a further significant increase in both beta-luteinizing hormone and follicle-stimulating hormone. In contradistinction, women in the second trimester of pregnancy showed a blunted response to the daily and pulsatile administration of gonadotropin-releasing hormone. Since the pituitary secretion of gonadotropin was functionally restored by the administration of exogenous gonadotropin-releasing hormone, possibly there is a lack of secretion of endogenous gonadotropin-releasing hormone during the first trimester of pregnancy. An increased negative feedback produced by increasing levels of plasma estradiol might be the cause of pituitary refractoriness to gonadotropin-releasing hormone during the second trimester of pregnancy.