Fertility on ice: an overview of fertility preservation for children and adolescents with cancer TOG 2021

Question 1

What is fertility preservation?

Answer 1

The preservation of an individual’s oocytes, sperm or gonadal tissue so that the individual may use them to have their own biological children in future.

Question 2

Which cancer treatments pose the greatest risk of gonadotoxicity?

Answer 2

Total body irradiation
Alkylating agents (cyclophosphamide, busulfan and chlorambucil)

Question 3

Irradiation above what Gy to the ovaries is associated with POI?

Answer 3

> 10Gy

Question 4

What % of male survivors of childhood cancer suffer azoospermia or oligospermia

Answer 4

azoospermia 30%
oligospermia 18%

Question 5

What fertility preservation can be offered to boys with cancer Dx?

Answer 5

Pubertal: Sperm cryopreservation

Prepubertal: Tesiticular tissue cryopreservation

Question 6

Advantage/disadvantages
Sperm cryopreservation

Answer 6

Ad: No delay in commencing treatment, noninvasive

Disad: May be difficult to produce sperm - anxiety, SE medication or cancer, religious beliefs.

Question 7

What fertility preservation can be offered to post pubertal boys with cancer Dx?

Answer 7

Oocyte/embryo cryopreservation

Ovarian tissue cryopreservation

In vitro maturation

Ovarian transposition

GnRH agonist

Question 8

What is cryopreservation/vitrificatino?

Answer 8

o Cyropreservation: cooling cells to sub-zerp. Halting biological activity,
o Vitrification – high conc of cryoprotectants and rapid cooling to avoid formation of ice crystals, improved viability of cryopreserved cells.

Question 9

Disadvantage of Oocyte/embryo cryopreservation

Answer 9

Requires ovarian stimulation and oocyte retrieval – stimulation takes 2 weeks and self-administer FSH injections, normally wait for start of menstral cycle but in cancer patients do at any time.

Risks
 Delay cancer Tx
 OHSS – young girls have high ovarian reserve
 Stimulation increase oestrogen levels – risk for oestrogen-dependent cancers – can use aromatase inhibitor based protocol as have less risk cancer
 TVUS required
 Lower oocyte retrival/birth rates than those with fertility preservation for non cancer reasons

Question 10

How is ovarian tissue cryopreservation achieved?

Answer 10

Lap surgery to remove all/part of ovary, cryopreservation for autotranplantation in future.

Question 11

Benefits ovarian tissue cryopreservation

Answer 11

No ovarian stimulation - treatment not delated

OTC does not require sexual maturity so can be performed on prepubertal girls

Autotrnsplantation - restore ovarian endocrine function

Question 12

Ovarian activity is restored in what % of women following transplantation. Median time for this to occur?

Answer 12

90% of women
4 months after transplantation
27% chance of pregnancy - can be natural conception

Question 13

Disadvantage OTC?

Answer 13

Ovarian tissue may harbour cancer cells. Accepted for solid tumour with no evidence of metastatic spread, risk of malignant cells in ovary is high for leukemia, so is controversial

Question 14

What is in vitro maturation?

Answer 14

Retrieval of immature oocytes from ovaries after no GnRH stimulation, maturation in lab, IVM may be done at time of collection or immature oocytes mat be cryopreserved with IVM at later stage.

Question 15

Advantages and disadvantages of in vitro maturatino

Answer 15

Ad: No ovarian stimulation, no delay in Tx/rosk OHH.

Disad: Few live births from this technique. Low birth rate than fresh oocytes.

Question 16

Main issue with testicular tissue cryopreservation?

Answer 16

Puberty herald maturation of germinal epithelium towards spermatids and mature sprem.
Retrival before puberty are unlikely to produce cells that can be used in ART.

Question 17

What is ovarian transposition?

Answer 17

Ovary+/- tube removed from uterus and attached to wall of abdomen away from radiation target area

Question 18

Efficacy of ovarian transposition?

Answer 18

50%
Radiation scattered and altered ovarian blood flow
No long term studies to assess clinical pregnancy.

Question 19

Use of GnRHa in FP?

Answer 19

During chemo used GnRHa tp suppress ovary activity to reduce negative impact on OR.
Only been studied in breast cancer.

Question 20

What is the Edinburgh selection criteria for FP

Answer 20

Age younger than 35 years

No previous chemotherapy or radiotherapy if aged 15 years or older at diagnosis, but mild, nongonadotoxic chemotherapy acceptable if younger than 15 years

A realistic chance of surviving for 5 years

A high risk of premature ovarian insufficiency (>50%)

Informed consent (from parents and, where possible, the patient)

Negative serology results for HIV, syphilis and hepatitis B

Not pregnant and no existing children