Combined GnRH-agonist/gonadotrophin stimulation for in-vitro fertilization

The occurrence of a premature luteinizing hormone (LH) surge during gonadotrophin stimulation for in-vitro fertilization leads to cancellation of the cycle. Moreover, insufficient follicular maturation is often caused by elevated basal gonadotrophin levels. Therefore, the gonadotrophin-releasing hormone (GnRH) agonist, D-Trp-6-LHRH, was applied to patients exhibiting premature LH surges, hyperandrogenaemia or incipient premature menopause. A total of 119 cycles were treated using a long-acting versus a short-acting GnRH agonistic analogue. In protocol 1, patients received daily s.c. injections of 100-500 micrograms of a short-acting compound. In protocol 2, a long-acting bolus of 3.2 mg was given i.m. Concomitant human gonadotrophin stimulation was started in protocol 1 after clinical and biochemical evidence of pituitary suppression and in protocol 2 after a fixed suppression interval of 14 days. In protocol 1, higher oestrogen levels were reached with more oocytes harvested. The pregnancy rate per transfer was increased from 3.5 to 18%, with most pregnancies occurring with protocol 1. The cancellation rate of 13.4% was mainly due to insufficient follicular development in patients in whom premature menopause was suspected. Hyperandrogenaemic patients with an elevated LH/FSH ratio exhibited the best follicular recruitment with the highest pregnancy rate of 25% per transfer. Thus, combined GnRH-agonist/gonadotrophin stimulation offers a causal treatment for patients susceptible to premature LH surges and for hyperandrogenaemic patients.