Table 2.

Summary of the suggested underlying mechanisms by which chemotherapy compromises follicular ovarian reserve (5, 7–13).

Proposed mechanism	Outline	Reference
“Accelerated” ovarian follicle maturation	Chemotherapy→ apoptosis of functioning ovarian follicles→ ↓estrogen, anti-Müllerian hormone→ ↑ gonadotropins → accelerated maturation of premature ovarian follicles→ apoptosis → gradual exhaustion of ovarian follicles deposit	Cui et al. (5) Roness et al. (7) Kalich-Philosoph et al. (8)
	Chemotherapy → ↑ activation of the PI3K/PTEN/Akt signaling pathway in oocytes and pregranulosa cells → phosphorylation of maturation mediators → apoptosis of mature follicles → gradual exhaustion of ovarian follicles deposit	Roness et al. (7) Kalich-Philosoph et al. (8) Adhikari et al. (9)
Direct quiescent follicle DNA damage	Alkylating agents, doxorubicin→ formation of DNA cross-links in non-dividing, dormant oocytes→ accumulation of DNA strand breaks→ pro-apoptotic intracellular pathways activation→direct apoptosis of quiescent follicles→ gradual exhaustion of ovarian follicles deposit	Bedoschi et al. (10) Soleimani et al. (11) Titus et al. (12)
Disrupted ovarian vascularization	Chemotherapy→ ovarian vascular spasm → ovarian ischemia related damage	Bedoschi et al. (10) Bar-Joseph et al. (13)
	Chemotherapy→fibrosis of the ovarian cortex→ compromised blood vessel formation→ ovarian ischemia related damage
	Chemotherapy→ inhibition of angiogenesis → reduced ovarian blood flow→ ovarian ischemia related damage