**13. Poor ovarian response**

The definition of 'poor response' in the literature is often based on a combination of factors, including the number of mature follicles, the number of oocytes retrieved and the peak estradiol level [138]. The cut-off levels for the number of follicles or oocytes that define poor response vary widely from study to study. Some authors feel that the definition of poor response should also include the degree of ovarian stimulation used and that a low oocyte number is detrimental only when high total dose of follicle stimulating hormone (FSH) has been administered [139]. Various endocrine and ultrasonographic markers and dynamic tests to assess ovarian reserve have been evaluated. Such tests include basal FSH on cycle day 3, clomiphene citrate challenge test, inhibin B, oestrogen, anti-Mullerian hormone, antral follicle counts and ovarian volume. The success of each test can be measured against ovarian response or live birth rate per cycle [140]. However, none of these tests has demonstrated a reliable predictive value and for many women poor ovarian response is not discovered until the first IVF cycle.

Poor response to gonadotropin stimulation occurs more often in older women, but may also occur in young women, regardless of the endocrinologic profile [141]. Poor responders have a significantly lower pregnancy rate per retrieval compared to normal to high responders in the same age group [138]. Although it is possible to have normal embryos and pregnancy in younger poor responders, the fertilization rate and quality of embryos in older poor responders are always low and the chance of achieving pregnancy in these patients is low. Poor responders also have an increased cycle cancellation rate due to retrieval of few or no oocytes and/or TFF. One of the major contributing factors for TFF after ICSI is ≤3 MII oocytes retrieved (Esfandiari *et al*., 2005a). The rate of fertilization failure increases as the number of injected oocytes decreases [142]. There is a higher chance of having no embryos for transfer and significantly lower pregnancy rates when less than five oocytes are retrieved compared to cases with ≥5 oocytes [143]. Limited information is available on IVM of immature oocytes retrieved from poor responders in conventional stimulation IVF/ICSI cycles and IVM is not a viable alternative to cancellation of IVF cycles in such patients [10].

Fecundity significantly decreases with increasing maternal age [144]. In a classic study of the Hutterite women, sterility increased from just over 10% at 34 years old to over 85% by the age of 44 years [145]. In women, all germ cells are formed during fetal life. The population of germ cells appears to rise steadily from 600 000 at 2 months post conception, reaching a peak of 6 800 000 at 5 months. By the time of birth, the number declines to 2 000 000 of which 50% are atretic. Of the 1 000 000 normal oocytes in the newborn infant, only 300 000 survive to the age of 7 years [146]. Continuous loss of oocytes occurs through the physiological process of follicular growth and atresia throughout life [147].

The incidence of TFF increases with age [10]. Older women are more likely to undergo multiple cycles, have decreased number of oocytes retrieved and a lower number of embryos transferred [9].
