title: [Ovulation induction with pulsatile gonadotropin-releasing hormone and continuous human menopausal gonadotropin in polycystic ovarian disease].
abstract: Various treatments have been applied to polycystic ovarian (PCO) type of anovulation. However, none of them was definitive in terms of the efficacy and side effects. Six anovulatory women of PCO type were treated with pulsatile gonadotropin-releasing hormone (GnRH) of various pulse intervals and continuous human menopausal gonadotropin (hMG). The efficacy and rationale of the treatments were discussed. The subjects were diagnosed PCO by GnRH test and/or laparoscopy. They did not ovulate with clomiphene, clomiphene-hCG and hMG-hCG therapies. Their pretreatment serum FSH and LH levels and FSH/LH ratios were 6.9 +/- 1.2 mIU/ml, 15.7 +/- 5.1 mIU/ml, and 0.54 +/- 0.19 (Mean +/- SD), respectively. The treatment consisted of 3 protocols: 1) pulsatile GnRH (5-10 micrograms/pulse) of 90 min interval, 2) pulsatile GnRH (5-10 micrograms/pulse) of 120 min interval and 3) continuous hMG (150 IU/day) through subcutaneous route. Follicular growth was monitored sonographically and an intramuscular bolus of 10,000 IU hCG was given when the dominant follicle reached 20 mm in diameter. During both GnRH treatments serum FSH levels and FSH/LH ratios did not elevate substantially. Serum LH, E2 and PRL levels elevated acutely and transiently during the initial phase of GnRH treatments. Follicular growth was observed in a small fraction of the cases, but none of them ovulated. In contrast, continuous hMG treatment induced significant elevation in serum FSH levels (8.2 +/- 1.7 mIU/ml; p less than 0.01) and FSH/LH ratios (1.73 +/- 0.57; p less than 0.001). Transient hyperprolactinemia was accompanied with the preovulatory E2 rise. All the cases ovulated and 3 singleton pregnancies followed. These findings draw conclusions as follows. Pulsatile GnRH administration may desensitize the pituitary presumably due to increased GnRH pulse frequency as a consequence of two independent pulse generators, intrinsic and exogeneous. It may induce transient hyperprolactinemia through a paracrine system between gonadotrophs and lactotrophs. As a due course pulsatile GnRH therapy is questionable for ovulation induction in cases with functioning hypothalamic-pituitary axis. The fact that continuous hMG effectively induced follicle maturation with elevated FSH/LH ratios suggested that FSH dominance might be a prerequisite for folliculogenesis. The fluctuating nature of gonadotropins might not be mandatory for folliculogenesis.
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008596:Menotropins / Q000008:administration & dosage*; D010062:Ovulation Induction; D010906:Pituitary Hormone-Releasing Hormones / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*
chemical_list: D010906:Pituitary Hormone-Releasing Hormones; D008596:Menotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone