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Fertility Preservation

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Fertility Preservation In Cancer Patients Barbara J. Stegmann, MD, MPH Assistant Professor Reproductive Endocrinology and Infertility University of Iowa – PowerPoint PPT presentation

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Title: Fertility Preservation


1
Fertility Preservation In Cancer Patients
Barbara J. Stegmann, MD, MPH Assistant
Professor Reproductive Endocrinology and
Infertility University of Iowa Barbara-Stegmann_at_ui
owa.edu
2
Patients diagnosed with cancer in US in 2005
4 under age 35
1,372,910 patients
55,000 under the age of 35
12,000 under the age of 19
Lee et al, J Clin Onc 2006
3
Estimated Number of Cancer Survivors in U.S
(1971 to 2004)
4
Cancer Fertility Crossroads
  • Increasing Cancer Survival Rates
  • Increased Emphasis on Quality of Life
  • New Fertility Preservation
  • Post-treatment Parenthood Options
  • Patients Need Information About
  • Fertility Risks Options

5
Are cancer patients interested in interventions
to preserve fertility?
  • Fertility preservation is of great importance to
    people diagnosed with cancer
  • Most cancer survivors prefer to have biological
    offspring despite serious concerns
  • Increased emotional distress in those who become
    infertile after cancer treatment
  • Long-term quality of life is affected by
    unresolved grief and depression
  • Patients may choose a less effective treatment
    strategy in order to avoid or reduce the risk of
    infertility

6
Objectives
  • What are the current and future options to
    preserve fertility in males?
  • What are the current and future options to
    preserve fertility in females?
  • Who will benefit from fertility preservation
    counselling?

7
Causes of Male Infertility
  • The disease itselfHodgkins Lymphoma
  • Retrograde ejaculation or anejaculation
  • 1o or 2o hormone insufficiency
  • Damage or depletion of germinal stem cells

8
Anti-tumor agents that can cause prolonged
azoospermia
Radiation (2.5 GY to testis) Cisplatin (500 mg/m2)
Chlorambucil (1.4 g/m2) Procarbazine (4 g/m2)
Cyclophosphamide (19 g/m2) Melphalan (140 mg/m2)
  • Currently do not know how new agents affect sperm
    production
  • New agents include oxaliplatin, irinotecan,
    monoclonal antibodies, tyrosine kinase inhibitors
    and taxanes

9
Current options for Preservation of Fertility in
Males
  • Sperm cryopreservation
  • Antegrade ejaculate
  • Retrograde ejaculate
  • Testicular aspirate (outpatient surgery)
  • Gonadal shielding during radiation
  • Testicular suppression with GnRH analogs or
    antagonists not effective

10
Use of cryopreserved sperm
  • 10-30 of the men who banked sperm before
    cancer treatment return to use the sperm
  • Storage fees are rarely the reason for specimen
    discard.

11
Couple Bear Child Using 14-Year-Old Frozen Semen
12
Before they got married, Rick explained to
Jessica all about his cancer history and the
possibility that he might be infertile. She was
not intimidated by the news. We knew we had
options, she said, referring to the banked
sperm. We had more anxiety when we went to do
this.
Quad City Times, Nov 11, 2010
13
Causes of Female Infertility
  • DNA damage to oocytes
  • Destruction of the primordial follicles
  • Hormonal imbalances due to damage to the
    pituitary
  • Damage to uterus, ovaries and tubes

14
Effect of Radiation on Female Fertility
  • Direct indirect damage to DNA of oocytes
  • Small primordial and growing follicles damaged
  • Damage to the pituitary

15
High Risk of Amenorrhea
  • Bendamustine
  • Busulfan
  • Carboplatin
  • Chlorambucil
  • Cisplatin
  • Cyclophosphamide
  • Dacarbazine
  • Isofamide
  • Mechlorethamine
  • Melphalan
  • Procarbazine
  • Temozolomide
  • Thiotepa


Fertile Hope, Fast Facts for Oncology
Professionals, 2007
16
Risk of ovarian involvement
LOW RISK
MODERATE RISK
  • Wilms
  • Lymphomas
  • Stage I-III breast CA (infiltrating ductal)
  • Nongenital rhabdomyosarcoma
  • Osteogenic sarcoma
  • Squamous cell cervix
  • Ewing sarcoma
  • Stage IV breast
  • Adeno cervix
  • Colorectal

HIGH RISK
  • Leukemia
  • Neuroblastoma
  • Stage IV lobular breast

Sonmezer Oktay Human Reprod Update 2004.
17
Oocyte Development
18
Assessing Ovarian Reserve in Cancer Patients
  • FSH
  • Late biomarker
  • Indirect measure of ovarian health

Lie Fong et al. Hum Reprod 200823(3)674-8.
19
Initiation of Puberty
20
Assessing Ovarian Reserve in Cancer Patients
  • Ovarian volume

21
Assessing Ovarian Reserve in Cancer Patients
  • Antral Follicle Count (AFC)

22
Assessing Ovarian Reserve in Cancer Patients
  • AMH (anti-mullerian hormone)

23
Assessing Ovarian Reserve in Cancer Patients
  • Cycle regularity - use caution
  • Regular cycles ?fertile
  • Amenorrhea ? Infertile
  • Remember to offer contraception when fertility
    is not desired

24
Options for Fertility Preservation
  • The Now
  • Embryo cryopreservation
  • Near Future
  • Oocyte cryopreservation
  • Still considered experimental
  • Long Range Planning
  • Ovarian tissue cryopreservation
  • Cytotoxic protectants

25
Embryo Cryopreservation
  • Most established technique for fertility
    preservation
  • Requires 8-12 days of ovarian stimulation
  • Retrieval is an outpatient surgical procedure
  • May delay treatment 2-6 weeks
  • Success rate varies, depending on females age

26
Limitations of embryo cryopreservation
  • Time
  • Need 2-6 weeks -gt may delay therapy
  • Relationship status
  • Must have partner or donor sperm
  • Age
  • Not acceptable for children
  • Cost
  • 12-15,000 / cycle and storage fees
  • Risks
  • Hyperstimulation syndrome
  • Exposure to higher level of estradiol

27
Oocyte cryopreservation
  • Reproductive age women without partners
  • Women with an ethical or religious objection to
    embryo storage
  • An option for pubertal girls

28
Limitations of oocyte cryopreservation
  • Time
  • Cost
  • Risks


Similar to embryo cryopreservation
Oocyte cryopreservation is technically challengi
ng
29
Ovarian Tissue Cryopreservation
  • Advantages
  • No partner required
  • No ovarian stimulation required
  • May be feasible for prepubertal children

30
Ovarian Tissue Cryopreservation
  • Tissue is removed laparoscopically and
    cryopreserved
  • Primordial and primary follicles
  • Reimplanted when ready to have children
  • Oocytes are matured in the lab and fertilized

31
Limitations of ovarian tissue cryopreservation
  • Large follicular loss due to ischemia (about 25
    of primordial follicles are lost)
  • Possibility of residual malignant cells
  • Oocytes arrested in prophase I so must undergo
    in-vitro maturation if not reimplanted
  • Cost
  • 12,000 for harvest, freeze
  • 10,000 for transplantation
  • -15,000 for IVF

32
Cytoprotective Agents
  • NRF2 activators
  • Sulforaphane
  • Amifostine
  • Trental/Vitamin E
  • Dexrazoxane

33
Cytoprotective Agents
  • GnRH analogs or antagonists
  • ? proven benefit
  • ? Lower incidence of premature ovarian failure
    and infertility in prepubertal girls receiving
    alkylator
  • Highly controversialbeing used without clear
    evidence of efficacy or understanding of
    risks/benefits

34
Cytoprotective Agents
  • GnRH analogs or antagonists
  • Theorhetical mechanisms
  • Downregulation of the ovary
  • Antiapoptotic
  • Decreases blood flow to ovary so less exposure

35
Ovarian Transposition
  • Oophoropexy offered with pelvic radiation is used
    for cancer treatment
  • Must be performed close to the time of radiation
    treatment (risk of remigration)
  • May be performed laparoscopically if laparotomy
    is not needed for treatment

36
Ovarian Transposition
  • Success rate judged by short-term menstrual
    function is 50.
  • Failure is attributed to scatter radiation,
    alteration of the ovarian blood supply and total
    radiation dose.
  • Ovarian repositioning may or may not be required.

37
Special considerations for pediatric cancer
patients
  • Impaired fertility difficult to conceptualize
  • Spermarche occurs at 13-14 years
  • Established methods (sperm and embryo
    cryopreservation) require BOTH patient assent and
    parental consent
  • Experimental methods should only be attempted
    under IRB-approved protocols

38
Average Treatment Costs
Nationally UIHC
Sperm Banking 1500 218 150/yr
Testicular tissue freezing 10,000 5500 150/yr
Embryo Freezing 10,000 10,000 - 11,000
Egg Freezing 8,000 NA
Ovarian Tissue Freezing 12,000 NA
GnRH analog treatment ? 500/mo
In Vitro Fertilization 10 14,000 11 - 13,000
Donor gametes or embryos 25,000 20 - 25,000
Adoption 2,500 35,000
Surrogacy 20 100,000 20 - 100,000
Pre-Treatment
Post-Treatment
39
Barriers to accessing care (From fertile HOPE
fertility resources for cancer patients)
  • Up to 90 of young cancer patients are at risk
    for infertility following treatment
  • lt25 of oncologists inform eligible patients
    about their risks and options
  • Fears and misconceptions exist from fertility
    treatments and the safety of pregnancy after
    cancer

40
Conclusions
  • Fertility preservation is often possible
  • Sperm and embryo cryopreservation are the only
    non-experimental procedures available.
  • A broader application of fertility preservation
    requires
  • Education
  • Provision of financial resources for these
    interventions
  • Better understanding of the risks associated with
    fertility preservation

41
Conclusions
  • Information is important, but do not give false
    hope
  • Consider referring to our study or our clinic for
    consultation
  • Fertility preservation should not be pursued at
    the expense of cancer treatment and overall
    welfare

42
  • Questions?
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