Ovarian tissue cryopreservation was first performed more than 20 years ago. The first live birth after ovarian tissue transplantation after cryopreservation was reported in 2004 [1] followed by a second one the following year [2]. Today, with more than 120 live births and a 30% success rate, this technique is no longer considered experimental. However, the evolution of oocyte and embryo vitrification techniques has limited the ovarian cryopreservation to a selected number of patients. The ASRM (American Society for Reproductive Medicine) recognizes the cryopreservation of oocytes and embryos as only valid methods for the preservation of fertility.

Premature ovarian failure (POF) can occur in woman spontaneously or due to iatrogenic causes. Chemotherapy and radiotherapy have significantly increased life expectancy in cancer patients but at the same time they can become deleterious for the ovarian function and reserve.

Chemotherapy treatments (Fig. 20.1) are divided into three categories of gonadotoxicity risk: low, medium, and high risk.

Cyclophosphamide is the agent which causes the greatest damage to oocytes and granulosa cells. The ovarian damage depends on patient’s age and on the type of treatment administered.

As far as radiotherapy is concerned it has been stated that a dose of 5–20 Gy administered to the ovary is sufficient to completely impair gonadal function, whatever the age of the patient [3, 4].

Patients who undergo bone marrow transplantation associated to total body irradiation and/or intensive chemotherapy, the percentage of POF after the treatment is nearly 100% [5–7].

Three options can be proposed to preserve fertility before radiotherapy or chemotherapy: oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. The vitrification of oocytes (in metaphase II) is the ideal technique in pubertal and adult age for the preservation of fertility in cases of benign diseases such as autoimmune diseases or in cases of neoplasia. Moreover, it is the only method that guarantees that no malignant cell is reintroduced when the oocytes will be used again. The embryo cryopreservation would be a better option because of the known oocyte loss at thawing but it requires the presence of a partner or donor sperm. Studies show a survival rate of mature oocytes after thawing of 90% and a 50% pregnancy rate. However, we must consider that in order to have a live birth, it is necessary to have at least 20 vitrified oocytes [5]. In both cases, the patient must be in pubertal age and the start of the chemotherapy has to be postponed for 2 weeks, the time interval needed to stimulate the ovaries and collect mature oocytes. In prepubertal patients or in patients with oncological diseases in which the beginning of chemotherapy cannot be delayed, ovarian tissue cryopreservation represents the only possibility of preserving fertility.

The indications for cryopreservation of ovarian tissue in case of malignant and nonmalignant diseases are summarized here below (Table 20.1) [8]. In gynecological neoplasia, proposing an ovarian cryopreservation should be taken into consideration before realizing a fertility preservation surgery and spare the uterus given the restriction in surrogacy. The indication for ovarian cryopreservation can be also considered in patients, especially children, who undergo a unilateral oophorectomy for nonmalignant diseases. Jadoul et al. in 2017 analyzed all ovarian cryopreservation cases realized in their institution between 1997 and 2013; in 545 cases, 17% were done for benign diseases as shown in Table 20.2 [9]. The indications of cryopreservation must be discussed in a multidisciplinary team after taking into consideration the type of treatment administered to the patient after the surgery and its gonadotoxic risk.

Table 20.1

Indications for cryopreservation of ovarian tissue in case of malignant and nonmalignant diseases (adopted from Donnez et al. [1])

(A) Malignant
(a) Extrapelvic diseases
	Bone cancer (osteosarcoma and Ewing sarcoma)
	Breast cancer
	Melanoma
	Neuroblastoma
	Bowel malignancy
(b) Pelvic diseases
	Non gynecologic malignancy
	Pelvic sarcoma
	Rhabdomyosarcoma
	Sacral tumors
	Rectosigmoid tumors
	Gynecologic malignancy
	Early cervical carcinoma
	Early vaginal carcinoma
	Early vulvar carcinoma
	Selected cases of ovarian carcinoma (stage IA)
	Borderline ovarian tumors
(c) Systemic diseases
	Hodgkin disease
	Non-Hodgkin lymphoma
	Leukemia
	Medulloblastoma
(B) Nonmalignant
	(a) Uni/bilateral oophorectomy
	Benign ovarian tumors
	Severe and recurrent endometriosis
	BRCA1 or BRCA2 mutation carriers

Table 20.2

Causes of ovarian cryopreservation [6]

	N(%) patients	N(%) deaths	N(%) autografts
Hematological pathology	191(35)	15(8)	11
Lymplioma	127(23)	6(5)
Leukemia	50(9)	9(18)
Benign	14(3)	0
Breast cancer	94(17)	5(5)
Sarcoma	51(9)	17(33)
Gynecological malignancy	33(6)	4(12)
Neurological malignancy	26(5)	7(27)
Gastrointestinal malignancy	16(3)	5(31)
Systemic disease	11(2)	0
Benign and borderline ovarian pathology	95(17)	0
Generic diseases	19(3)	0
Other	9(2)	1(11)

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