Prediction of ovarian damage

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The ability to measure the likely toxic impact of chemotherapy and radiation exposure regimes on the ovaries of pre- and post-pubertal girls would enable us to predict how such treatments will affect the future reproductive lifespan and fertility of these individuals (Singh, Davies and Chatterjee 2005). Tests of ovarian damage must assess the number of primordial follicles present in the ovary (the ovarian reserve) rather than the number of more advanced growing follicles and mature oocytes, as the later stages of follicle and oocyte development are less likely to survive the treatment. Hundreds of thousands of primordial follicles are present in the ovaries of young patients (Gougeon, Echochard and Thalabard 1994); of these follicles only 400-500 would ovulate during the reproductive lifespan of a woman. The usual fate of the vast majority of the follicles present in the ovary is therefore degeneration through a process termed apoptosis (Gosden and Spears 1997). There is, therefore, a vast redundancy in the ovarian reserve and a significant proportion of the follicles and oocytes present in a

Table 5.1 Treatment options for preservation of fertility in young, female cancer patients

Treatment options



Prediction of the impact

In vitro exposure

All patients'

of chemo-and

diagnostic study

radiotherapy on the

Exposure studies in

All patients

lifespan of the ovary

model species

Measurement of ovarian

All patients


Reduction of the risk of

Ovarian transposition

Adults and adolescents

ovarian damage

GnRH agonist or

All patients

antagonist co-treatment

Oral contraceptive pill

Adults and adolescents

Preservation and

Cryopreservation of


restoration of fertility

embryos after IVF

Egg donation


Cryopreservation ofMII

Adults and adolescents


Cryopreservation of GV

All patients


Cryopreservation of

All patients

ovarian tissue

Note a All patients = adults, adolescents, and pre-pubertal girls.

young ovary can be lost as a consequence of treatments without unduly compromising the future fertility of the individual. In support of this concept, there are numerous reports ofyoung women who suffer a transient loss of reproductive cyclicity following cancer treatment before their hormonal and reproductive cycles are re-established and their natural fertility is restored (Meirow 2000). The ability to assess accurately the ovarian reserve in these individuals, both before and after their cancer treatment, would provide these patients with reassurance that their cancer treatment has not induced a premature menopause.

Ovarian follicle reserve can be assessed in a number of ways but much debate exists as to the accuracy and reliability of the different methods

(Gulekli etal. 1999). Histological assessment of surgically recovered ovarian tissue has been used to assess the density of primordial follicles in the human ovary (de Bruin etal. 2002, 2004). This approach relies on the fixed tissue sample being representative of the whole of the ovary, which unfortunately is frequently not the case. Alternatively, ultrasound measurement of ovarian volume has been proposed as an indicator of ovarian function in women post-cancer treatment (Sharara and McClamrock 1999). Similarly, measurement of the ovarian hormone Inhibin B, which is secreted into the peripheral circulation by the granulosa cells of small antral follicles, has been suggested as an index of ovarian function (Hall, Welt and Cramer 1999; McLachlan etal. 1986). While the measurement of ovarian volume and Inhibin B levels are useful, both of these techniques measure the number of advanced antral follicles in the ovary and thus only provide a snapshot of ovarian function at the time of the assay. Neither of these methods provides long-term insight into the reproductive lifespan of the individual as they do not measure the number of primordial follicles left in the ovary. A far more informative approach, which has been successfully applied to the prediction of ovarian reserve in adult cancer survivors, is the measurement of the systemic level of Anti-Mullerian Hormone (AMH) (Bath etal. 2003). The concentration of AMH in the blood accurately predicts the reproductive lifespan as AMH is synthesized and secreted only by primordial follicles.

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