Portal de Periódicos da CAPES

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

1997; Oxford University Press; Volume: 12; Issue: 11 Linguagem: Inglês

10.1093/humrep/12.11.2359

1460-2350

Mark A. Damario, Larry I. Barmat, H.-C. Liu, Owen Davis, Zev Rosenwaks,

Reproductive Health and Technologies

Certain patients have a tendency for high response to gonadotrophin therapy which is often not ameliorated with prior gonadotrophin-releasing hormone agonist (GnRHa) suppression. As a result, these patients are frequently cancelled 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 be particularly sensitive to exogenous gonadotrophin therapy. We have developed a protocol which is effective in improving IVF outcome in high responder 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 contraceptive administration. Low-dose gonadotrophin stimulation is then initiated on the third day of withdrawal bleeding in the form of either human menopausal gonadotrophins or purified urinary follicle-stimulating hormone at a dosage of 150 IU/day. Over a 5 year period, we reviewed our experience utilizing this dual method of suppression in 99 cycles obtained in 73 high responder patients. There were only 13 cancellations prior to embryo transfer (13.1%). The clinical and ongoing pregnancy rates per initiated cycle were 46.5 and 40.4% respectively. Only eight patients experienced mild-moderate OHSS following treatment. For those patients who had undergone previous IVF-embryo transfer cycles at our centre, significant improvements were noted in oocyte fertilization rates, embryo implantation rates and clinical/ongoing pregnancy rates with this protocol. Hormonal analyses revealed that the chief mechanism may be through an improved luteinizing hormone/follicle-stimulating hormone ratio following dual suppression. An additional feature of this dual method of suppression is significantly lower serum androgen concentrations, particularly dehydroepiandrosterone sulphate.Presented is a protocol that is effective in improving in vitro fertilization (IVF) outcome in women with a tendency for a high response to gonadotrophin therapy. High responders to exogenous gonadotrophin therapy show recruitment of large numbers of follicles, rapid estradiol responses, and a significant cycle cancellation rate due to the potential risk of hyperstimulation during IVF-embryo transfer attempts. Women with polycystic ovarian syndrome are especially sensitive to exogenous gonadotrophin therapy. The protocol entails 25 days of oral contraceptive (OC) use, followed by 1 mg/day of subcutaneous leuprolide acetate overlapped with the final 5 days of OC therapy. On the third day of withdrawal bleeding, gonadotrophin stimulation is initiated through either human menopausal gonadotrophins or purified urinary follicle-stimulating hormone (150 IU/day). This approach permits normalization of the luteinizing hormone/follicle-stimulating hormone ratio and reduces ovarian androgen concentrations, while circumventing the initial gonadotrophin flare response. This protocol was tested in a retrospective review (1990-94) of 99 cycles from 73 high-responder women treated at a US infertility center. There were only 13 cancellations (13.1%) prior to embryo transfer. The clinical and ongoing pregnancy rates per initiated cycle were 46.5% and 40.4%, respectively. Only 8 women experienced ovarian hyperstimulation syndrome after treatment. Among women who had undergone previous IVF embryo transfer cycles at the center, the present regimen was associated with significant improvements in oocyte fertilization rates, embryo implantation rates, and pregnancy rates.