Freezing in Patient with Cancer

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© Springer Nature Switzerland AG 2020
A. Malvasi, D. Baldini (eds.)Pick Up and Oocyte Managementdoi.org/10.1007/978-3-030-28741-2_20



20. Oocytes Freezing in Patient with Cancer



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


(1)
Department of Obstetrics, Gynaecology and Reproductive Medicine, Misericordia Hospital, Grosseto, Italy

(2)
Center of Medically Assisted Procreation, MOMO’ fertiLIFE, Bisceglie, Italy

(3)
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy

(4)
Department of Obstetrics and Gynecology, GVM Care and Research Santa Maria Hospital, Bari, Italy

(5)
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.

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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

 

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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