1. Fertility Preservation
in Cancer Patients
Dr. Khaled R Darhouse, MRCOG
Consultant Obstetrician & Gynaecologist
Reproductive Medicine & Assisted Conception
King Abdulaziz University Hospital
Jeddah – Saudi Arabia

2. The Gonads
• The primary function of both ovaries and
testis is REPRODUCTION
• Reproduction is the passage of parental
genetic material onto the next generation

3. Life Expectancy
• In 1900 the average life expectancy of men
was 46.3 years and of women was 48.3 years.
• At the turn of the millennium men now expect
to live to be 73.8 and women to be 79.5 years
old.
• In a hundred years life expectancy has nearly
doubled.

4. National Geographic Magazine
May 2013
• THIS BABY WILL LIVE TO
BE 120
• New science could lead to
long lives

5. Longer life
• The longer the people live the more they’ll
expect to get cancer.
• Advantages in cancer treatment over the past
two decades have led to remarkable
improvements in survival rates.
• Indeed, during the past 5 years, the overall
death rates from cancer have fallen by more
than 1.6% per year.

6. General Fertility Preservation
• Women are increasingly postponing
childbearing to later in life for social,
career or financial reasons
• Incidence of most cancers increase with age

7. Cancer Fertility Preservation
• In women, ~10% of cancers occur in those <45
years old. Chemotherapy, radiotherapy and
bone marrow transplantation can cure >90%
of girls and young women with diseases that
require such treatments.
• However, these treatments can result in
premature ovarian failure, depending on the
follicular reserve, the age of the patient and
the type and dose of drugs used.

8. Improved Five Year Survival
(1966 -2000)

9. Five Year Survival
Childhood Cancers

10. Cure for Children but at a Cost
• Sustain and improve survival rates
• Minimise late effects
• Treatment is in conflict with normal childhood
growth and development

11. Risk Assessment for Fertility
Preservation
• Intrinsic Factors
• Health status of the patient
• Consent of patient or parents
• Assessment of ovarian reserve
• Extrinsic Factors
• Nature of planned treatment
• Available time
• Availability of expertise
Wallace H, Critchley H and Anderson R JCO
2012

12. Ovarian Reserve

13. Infertility Risk Factors
• Radiotherapy
• Irradiation of field of ovaries or testis
• Total body irradiation
• Chemotherapy
• Busulphan
• Cyclophosphamide
• Melphalan
• Mustine
• Procarbazine

14. Gonadotoxicity
Presentation Copyright: Dr. Khaled R Darhouse
Cytotoxic agents according to the degree of gonadotoxicity
High risk Intermediate risk Low/no risk
Cyclophosphamide Doxorubicin Methotrexate
Busulfan Cisplatin Bleomycin
Melphalan Carboplatin 5-Fluorouracil
Chlorambucil Actinomycin-D
Dacarbazine Mercaptopurine
Procarbazine Vincristine
Ifosfamide
Thiotepa
Nitrogen mustard
Reference: Lobo R; N Engl J Med2005 353,64–73.

15. Infertility Risk
• Low Risk (<20%)
• ALL
• Wilms’ tumour
• Brain tumours (RTx <24Gy)
• Soft tissue sarcomas
• Hodgkin’s lymphoma I/II

16. Infertility Risk
• Medium Risk
• AML
• Osteosarcoma
• Ewing’s sarcoma II/III
• Nuroblastoma
• Brain tumours (RTx > 24Gy)
• Hodgkin’s lymphoma III/IV

17. Infertility Risk
• High Risk (<80%)
• Total Body Irradiation
• Pelvic / testis irradiation
• Pre-BMT chemotherapy
• Ewing’s tumour IV
• Pelvic Hodgkin’s lymphoma

18. Radiation-Induced Ovarian Damage
• Human Oocyts
• Primordial follicles
• LD 50 <2 Gy
Wallace, Thompson and Kelsey, Hum
Reprod 2003

19. Radiation-Induced Ovarian Damage
• Human Oocyts
• Primordial follicles
• LD 50 <2 Gy

20. Effect and mean ovarian sterilizing
doses of radiotherapy at increasing age
• On a 7 years old 19 Gy
are needed to
completely deplete the
primordial follicle and
sterilize the patient
• At the age of 42 only 11
Gy are needed to
render the patient
sterile
Wallace H et al IJRBP (2005)

21. Uterine volume and age at irradiation
Bath et al BJOG (2005)

22. Uterine function after
cancer treatment
• Uterine damage, manifest by impaired growth
and blood flow, is likely a consequence of
pelvic irradiation.
• Uterine volume correlates with age at
irradiation.
• Exposure to pelvic irradiation is associated
with increased miscarriage, mid-trimester
pregnancy loss, preterm labour low birth
weight and post-partum haemorrhage.

23. Sex Hormone Therapy for Childhood
Cancer Survivors
• The most appropriate dose and route of
administration of sex hormone replacement to
young women with ovarian failure after pelvic
irradiation that provides adequate
concentrations of oestrogen to ensure optimal
uterine growth during adolescence has not yet
been established

24. OPTIONS OF FERTILITY PRESERVATION
• Envolves: Oncologists, Paediatricians,
Gynaecologists and Urologist/Andrologists
• Men:
• Sperm cryopreservation
• Women:
• Embryo cryopreservation
• Oocyte cryopreservation
• Ovarian tissue cryopreservation

25. OPTIONS OF FERTILITY PRESERVATION
• In pre-pubertal men testicular tissue
cryopreservation is experimental, but is the
only option currently available
• Sperm cryopreservation is a well established
and successful method routinely used.

26. OPTIONS OF FERTILITY PRESERVATION

27. OPTIONS OF FERTILITY PRESERVATION
• Ovarian function suppression
• Oral contraceptive pills
• GnRHa
• Embryo cryopreservation
• Well-established with good success
• Married
• Post-pubertal
• Delay in cancer treatment
• Legal issues

28. OPTIONS OF FERTILITY PRESERVATION
• Oocyte cryopreservation
• Mature oocytes
• Immature oocytes with IVM
• Post-pubertal
• Delay in cancer treatment
• Ovarian tissue cryopreservation
• Pre-pubertal / Post-pubertal
• No delay in cancer treatment
• Expertise

29. Mature Oocyte Cryopreservation
• Need for a stimulated cycle
• Tailored stimulation protocols
• GnRHa trigger
• Should not delay chemo/radiotherapy
• Disastrous consequences with complications
• Harvest of good quality oocytes should be
expected
• Not recommended after chemotherapy is
initiated

30. Mature Oocyte Cryopreservation
• Survival rate of vitrified oocytes is now
approximately 96.9%
• Pregnancy rates after oocyte vitrification
• 10 oocytes = 40%
• 12 oocytes = 60%
• 20 oocytes = 90%

31. Ovarian Tissue Cryopreservation
• Percentage of patients undergoing OTC:
• 96.2% of patients were < 35 years
• 52.5% of patients were < 24 years
• 17.2% of patients were < 14 years

32. Ovarian Tissue Cryopreservation
• Harvesting by laparotomy or laparoscopy
• How much of the ovarian cortex should be
removed?
• Size and thickness of cortical strips
• Cellular injury and damage
• Hypoxia
• Dehydration
• Freezing
• Slow freezing or vitrification?

33. Ovarian Tissue Cryopreservation
• Re-implantation could be either orthotopic or
hetrotopic
• More than 50% of primordial follicles are lost
due to hypoxia
• Thawing process injury
• High FSH and low AMH deplete surviving
primordial follicles

34. Harvesting and orthotopic re-
implantation of OTC

35. FSH Levels Post-Orthotopic
reimplantation

36. LH, FSH and E2 levels post
reimplantation of OTC

37. Ovarian Tissue Cryopreservation
• Orthotopic reimplantation allows for
spontaneous pregnancy
• Hetrotopic reimplantation necessitates IVF-
ICSI
• Major concern is reintroduction of malignant
cells after remission / cure.

38. Ovarian Tissue Cryopreservation

39. Ovarian Tissue Cryopreservation
• It is unknown how many cases of
reimplantation were carried out throughout
the world
• In a series of 60 reported cases the live birth
rate is 23%
• Young children are the ideal candidates
• No pregnancies reported following the
reimplanation of ovarain tissue harvested pre-
pubertally

40. The Future
• In vitro follicular maturation after ovarian
tissue culture
• Isolated primordial follicle culture in the lab
• Artificial ovaries

41. The Future
• Stem cell gamete production
• Experimental success in producing both eggs and
sperms
• Successful in producing normal and fertile mice
• Must pass rigorous testing
• Might be available in at least 10 years
• Lyophilization and Freeze-Drying
• Eggs
• Sperms
• Embryos

42. Conclusion
• Fertility preservation has become an
established branch of reproductive medicine.
• Multidisciplinary team approach and
individualisation of cases are key to its
success.
• Fertility preservation should be discussed with
men and women in the fertile age group who
are about to embark in cancer treatment

43. Conclusion
• Fertility preservation gives hope in future
reproduction and hope of a life after cancer.
• Embryo freezing is most successful method to
date.
• For prepubertal men and women gonadal
tissue freezing is the only available method
availlable.
• Many new promising methods wil be available
in the near future.

44. Thank You
Dr. Khaled R Darhouse, MRCOG
Consultant Obstetrician & Gynaecologist
Reproductive Medicine & Assisted Conception
King Abdulaziz University Hospital
Jeddah – Saudi Arabia