Poor Responders

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Poor responders to exogenous gonadotropins require markedly increased quantities of gonadotropins to obtain multifollicular development. Moreover, the number of oocytes, fertilization rates, embryo quality, and pregnancy rates are all decreased in this patient population. The incidence of poor response varies from 5% to 18% of unselected IVF patients (70). Poor response to gonadotropins is a result of diminished ovarian reserve. The most important cause is advanced female age. An age-related decline in fecundity, from 35 years in particular, has been observed in IVF. Other causes are prior chemotherapy, irradiation, ovarian surgery, severe endometriosis, autoimmune disease, or idiopathic. Some patients present with unexplained infertility and regular ovulatory cycles.

It is ideal to identify these patients before initiation of hormonal treatment for IVF. In this way, the patients can be counseled concerning the lower chances for pregnancy and stimulating protocols can be modified to lower the risk of cancellation and improve pregnancy rates. In 1987, Navot et al. (71) described the clomiphene citrate challenge test, a test measuring serum FSH levels before (day 3) and after day 10, the administration of 100 mg of clomiphene citrate on cycle days 5-9. They found that patients with an exaggerated FSH response, despite normal E2 response, had diminished ovarian reserve. They suggested that diminished capacity of the granulosa cells to secrete inhibin could explain the discrepancy between E2 and FSH response. This test was found to be a reliable method for predicting IVF-ET outcome. Later, several studies have shown that elevated day 3 serum concentrations of FSH (<6.5-15 IU/L) and/or E2 (<80 pg/ml) have poor pregnancy outcomes with fertility therapy (72). Martin et al. (73) evaluated 1868 cycles and found that no pregnancies occurred if day 3 FSH was >20 IU/L at least in two cycles, but if it happened just once, the pregnancy rate was 5.6%. Recently, Seifer et al. (74) found that women with low day 3 serum inhibin B concentrations (<45 pg/ml) demonstrated a poorer response to ovulation induction and IVF-ET treatment relative to women with high day 3 inhibin B.

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