Current state and controversies in fertility preservation in women with breast cancer

Table 1 The risk of infertility and mechanism of damage associated with chemotherapeutic agents that are commonly used in breast cancer treatment

Chemotherapeutic agent	Class	Mechanism of action	Cell cycle effect	Risk of infertility
Cyclophosphamide	Alkylating agent	DNA cross-link formation and double strand breaks that result in inhibition of DNA function and synthesis leading to cellular apoptosis	Cell cycle non-specific	High risk
Doxorubicin Epirubicin	Anthracyclines	Inhibition of DNA synthesis and function due to inactivation of DNA topoisomerase II, free oxygen radical formation and induction of DNA double-strand breaks	Cell cycle non-specific	Medium risk
Carboplatin	Platinum analog	Inhibition of DNA synthesis and function via intra- and interstrand DNA cross-link formation by covalent binding to genome	Cell cycle non-specific	Medium risk
Paclitaxel Docetaxel	Taxanes	Inhibition of mitotic division by binding to microtubules with enhancement of tubulin polymerization	M phase	Low risk
Methotrexate	Antimetabolites	Inhibition de novo purine nucleotide synthesis by inactivation of dihydrofolate reductase	S phase	Low risk
5-fluorouracil		Inhibition of DNA synthesis and function via inactivation of Thymidylate synthase and alteration in RNA processing	S phase	Low risk
Trastuzumab	Monoclonal antibodies	Blockage of Human epidermal growth factor receptor 2 subdomain IV, antibody dependent cellular toxicity	NA	Low or no risk
Pertuzumab		Blockage of Human epidermal growth factor receptor 2 subdomain II, antibody dependent cellular toxicity

Table 2 Common adjuvant chemotherapy regimens for breast cancer and their impact of fertility

Chemotherapy regimen	Risk of amenorrhea or infertility
	Age ≤ 35 yr	Age >35 yr
CMF	4%-40%	80%-100%
CEF	47%	80%-100%
CAF	No data	30%
AC	13.90%	68.20%
AC-T	9%-13%	65%-67%
AC-TH	0-14%	56%-67%

A: Doxorubicin; C: Cyclophosphamide; E: Epirubicin; F: 5-Fluorouracil; H: Trastuzumab; M: Methotrexate; T: Paclitaxel.

Table 3 Fertility Preservation options for reproductive age women with breast cancer

Fertility preservation option	Current status	Advantages	Disadvantages
Embryo Cryopreservation	Established	Highest cumulative pregnancy rates	Requires about two weeks delay in the initiation of cancer treatment
			Requires hormonal stimulation for oocyte retrieval
			Requires in vitro fertilization with male partner or donor sperm
Oocyte Cryopreservation	Established	No need for male partner or sperm donor	Requires about two weeks delay in the initiation of cancer treatment
			Requires hormonal stimulation for oocyte retrieval
Ovarian Tissue Cryopreservation and Transplantation	Currently experimental, may change as success rates are rising	No need for hormonal stimulation	Requires outpatient laparoscopic surgery for ovarian tissue harvesting and subsequent transplantation
		No need to significantly delay in the initiation of chemotherapy
		No need for male partner or sperm donor