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Several growth factors augment the ovarian response to gonadotrophins and growth hormone is known to regulate the production of insulin-like growth factor-1. With this in mind, 20 women who had previously responded sub-optimally to standard ovarian stimulation regimens for in-vitro fertilization and embryo transfer (IVF-ET) were recruited into a randomized trial to study the effect of co-treatment with growth hormone (Norditropin, Novo Nordisk Gentofte A/S). Intramuscular injections of growth hormone (24 IU) or placebo were given on alternate days concurrently with the same daily dosage of gonadotrophin as administered in the patient's pretreatment cycle. Overall, there was no improvement in the ovarian response to the growth hormone-augmented regimen of stimulation although there was a tendency for the development of more follicles (P = 0.06). When the results from the patients with ultrasound-diagnosed polycystic ovaries were analysed separately, however, more follicles developed (P = 0.04), more oocytes were collected (P = 0.03) and there was a trend towards higher urinary oestrogen production following growth hormone therapy. There was no improvement in the ovarian response in patients with normal ovaries. The treatment was not associated with any adverse effects. We conclude, therefore, that in a subgroup of patients who respond sub-optimally to standard ovarian stimulation regimens for IVF-ET and who have ultrasound-diagnosed polycystic ovaries, systemic growth hormone is an effective adjunctive therapy.

ABSTRACT

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.

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