Freezing in Patient with Cancer

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© Springer Nature Switzerland AG 2020
A. Malvasi, D. Baldini (eds.)Pick Up and Oocyte

20. Oocytes Freezing in Patient with Cancer

Fabrizio Signore1  , Raffaella Votino1  , Evangelos Sakkas1  , Domenico Baldini2  , Simona Zaami3 and Antonio Malvasi4, 5  

Department of Obstetrics, Gynaecology and Reproductive Medicine, Misericordia Hospital, Grosseto, Italy

Center of Medically Assisted Procreation, MOMO’ fertiLIFE, Bisceglie, Italy

Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy

Department of Obstetrics and Gynecology, GVM Care and Research Santa Maria Hospital, Bari, Italy

Laboratory of Human Physiology, Phystech BioMed School, Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Russia



Fabrizio Signore (Corresponding author)


Raffaella Votino


Evangelos Sakkas


Domenico Baldini


Antonio Malvasi

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.


Fig. 20.1

Categories of chemotherapy associated to gonadotoxicity risk

The low-risk group includes:

  • methotrexate

  • 5-fluorouracil

  • vincristine

  • bleomycin

  • actinomycin D

  • mercaptopurine

The medium-risk group includes:

  • doxorubicin

  • cisplatin

  • carboplatin

The high-risk group includes:

  • cyclophosphamide

  • chlorambucil

  • nitrogen mustard

  • dacarbazine

  • ifosfamide

  • thiotepa

  • melphalan

  • busulfan

  • procarbazine (Fig. 20.1)

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% [57].

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






Bowel malignancy

(b) Pelvic diseases


Non gynecologic malignancy


Pelvic sarcoma




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





(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
















Breast cancer








Gynecological malignancy




Neurological malignancy




Gastrointestinal malignancy




Systemic disease




Benign and borderline ovarian pathology




Generic diseases








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Mar 28, 2021 | Posted by in OBSTETRICS | Comments Off on Freezing in Patient with Cancer
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