Dual suppression with oral contraceptives and gonadotrophin releasing- hormone agonists improves in-vitro fertilization outcome in high responder patients

Certain patients have a tendency for high response to gonadotrophin therapywhich is often not ameliorated with prior gonadotrophin- releasing hormoneagonist (GnRHa) suppression. As a result, these patients are frequentlycancelled and often experience ovarian hyperstimulation syndrome (OHSS)episodes during in-vitro fertilization (IVF)-embryo transfer cycles.Patients with polycystic ovarian syndrome (PCOS) have been noted to beparticularly sensitive to exogenous gonadotrophin therapy. We havedeveloped a protocol which is effective in improving IVF outcome in highresponder patients, including those with PCOS. Oral contraceptive pills(OCP) are taken for 25 days followed by s.c. leuprolide acetate, 1 mg/day,which is overlapped with the final 5 days of oral contraceptiveadministration. Low-dose gonadotrophin stimulation is then initiated on thethird day of withdrawal bleeding in the form of either human menopausalgonadotrophins or purified urinary follicle-stimulating hormone at a dosageof 150 IU/day. Over a 5 year period, we reviewed our experience utilizingthis dual method of suppression in 99 cycles obtained in 73 high responderpatients. There were only 13 cancellations prior to embryo transfer(13.1%). The clinical and ongoing pregnancy rates per initiated cycle were46.5 and 40.4% respectively. Only eight patients experienced mild-moderateOHSS following treatment. For those patients who had undergone previousIVF-embryo transfer cycles at our centre, significant improvements werenoted in oocyte fertilization rates, embryo implantation rates andclinical/ongoing pregnancy rates with this protocol. Hormonal analysesrevealed that the chief mechanism may be through an improved luteinizinghormone/follicle-stimulating hormone ratio following dual suppression. Anadditional feature of this dual method of suppression is significantlylower serum androgen concentrations, particularly dehydroepiandrosteronesulphate.