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Oncofertility Oncofertility Preserving the Future Preserving the Future Nicole C. Rosipal, RN, MSN, PNP Nicole C. Rosipal, RN, MSN, PNP

Oncofertility Preserving the Future Nicole C. Rosipal, RN, MSN, PNP

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OncofertilityOncofertilityPreserving the FuturePreserving the Future

Nicole C. Rosipal, RN, MSN, PNPNicole C. Rosipal, RN, MSN, PNP

ObjectivesObjectives Incidence of cancer and survivorship among Incidence of cancer and survivorship among Adolescent and Young Adult (AYA) Adolescent and Young Adult (AYA) populationpopulation

Survivorship and significance of fertilitySurvivorship and significance of fertility Effects of cancer and cancer treatment on Effects of cancer and cancer treatment on fertilityfertility

Assessment of fertilityAssessment of fertility Age appropriate fertility preservation Age appropriate fertility preservation options options – Standard and ExperimentalStandard and Experimental

Key considerations when discussing Key considerations when discussing fertility with patients and familiesfertility with patients and families

Cancer and Survivorship Cancer and Survivorship Among Adolescent and Among Adolescent and

Young AdultsYoung Adults Approximately 70,000 Adolescent and Young Approximately 70,000 Adolescent and Young Adult (15-39) and 10,000 children (<15) Adult (15-39) and 10,000 children (<15) are diagnosed with cancer each yearare diagnosed with cancer each year

Childhood cancer survivorship > 70%Childhood cancer survivorship > 70% 1 of 900 individuals in U.S. between 15-45 1 of 900 individuals in U.S. between 15-45 is a childhood cancer survivor is a childhood cancer survivor

Approximately 270,000 cancer survivors Approximately 270,000 cancer survivors originally diagnosed less than 21 years of originally diagnosed less than 21 years of age are currently living in the United age are currently living in the United StatesStates

InfertilityInfertility

““Inability to conceive after 1 year of Inability to conceive after 1 year of intercourse without contraception”intercourse without contraception”

AzoospermiaAzoospermia– No measurable level of sperm in semenNo measurable level of sperm in semen– Obstructive vs. issue with Obstructive vs. issue with spermatogenesisspermatogenesis

Damage to oocyte, follicles or uterusDamage to oocyte, follicles or uterus – Immediate menopause Immediate menopause – Premature menopausePremature menopause

Infertility and General Population

Statistics– 6.1 million Americans – In 2002, 7% of women infertile

Multi-factorial causes– Men– Women– Both

Sexually transmitted diseases Lifestyle factors – smoking, alcohol, obesity

American Society of American Society of Clinical Oncology (ASCO) Clinical Oncology (ASCO)

GuidelinesGuidelines Panel reviewed literature spanning 1997 to 2005Panel reviewed literature spanning 1997 to 2005 Fertility preservation is of Fertility preservation is of great importancegreat importance Lack of knowledge and comfort of health care Lack of knowledge and comfort of health care teamteam

Effects of infertility resulting from cancer Effects of infertility resulting from cancer treatment:treatment:– Psychosocial and emotional distressPsychosocial and emotional distress– Loss of masculinity or femininityLoss of masculinity or femininity– Most survivors prefer to have biological childrenMost survivors prefer to have biological children

Survivors as ParentsSurvivors as Parents– Experience with illness can enrich their roleExperience with illness can enrich their role– High value on family closenessHigh value on family closeness

2006 ASCO Guidelines2006 ASCO Guidelines

““Oncologists should address the Oncologists should address the possibility of infertility with possibility of infertility with patients treated during their patients treated during their reproductive years and should reproductive years and should be considered as early as be considered as early as possible in the treatment possible in the treatment planning”planning”

Urban Legends and CautionUrban Legends and CautionMalesMales

Azoospermia is potentially for life, not Azoospermia is potentially for life, not short termshort term

Can still get someone pregnant!Can still get someone pregnant!– Sperm production can return immediately or Sperm production can return immediately or many years after cancer treatmentsmany years after cancer treatments

Pubertal development does not equal fertilityPubertal development does not equal fertility

Caution!Caution!– Sexually transmitted diseasesSexually transmitted diseases

Urban Legends and CautionFemales

A “period” does not define fertilityA “period” does not define fertility– Amenorrhea is not a definite sign of Amenorrhea is not a definite sign of infertilityinfertility

– Return of a period does not equal fertilityReturn of a period does not equal fertility

Cancer treatment can take years off of Cancer treatment can take years off of the biological clockthe biological clock

Caution!Caution!– STD’sSTD’s

Cancer and Infertility Cancer and Infertility MenMen

Risk is multifactorialRisk is multifactorial– AgeAge– DiseaseDisease– Cancer treatment regimenCancer treatment regimen– Pre-existing conditionsPre-existing conditions

Function of testicle effectedFunction of testicle effected Currently 15-30% of survivors are Currently 15-30% of survivors are sterilesterile

Cancer has been documented to have Cancer has been documented to have effect on quantity and quality of effect on quantity and quality of sperm.sperm.

A Word About Prepubertal Males

Radiation less damaging than chemotherapy

No protective effect against chemotherapy induced gonadal damage

Assessment of FertilityPrior to Beginning Cancer

Treatment Male

Tanner StagingTanner Staging–Related to secondary sexual Related to secondary sexual characteristicscharacteristics

–Average ageAverage age Spermatogenesis - 13 y.o. Spermatogenesis - 13 y.o. Completion of puberty - 15 y.o.Completion of puberty - 15 y.o.

Semen Analysis

Proportion of Patients Proportion of Patients with a Normal Semen with a Normal Semen

AnalysisAnalysisDiagnosis

% Nl

Brain 0

HL 33.3

Leukemia 9.1

Testicular

22.5

Sarcoma/ST

25

NHL 18

Other 0Grey 14-18

yo

White

>18 yo

Overall – 21.1% with normal semen analysis

High Risk for AzoospermiaTotal Body Irradiation (TBI)

Stem Cell Transplant (SCT)

Testicular radiation >2.5 gy men >6 gy boys

Testicular Cancer, ALL, Non-Hodgkin Lymphoma

Alkylating Chemotherapy for SCT conditioning Cyclophosphamide Busulfan Melphalan

SCT Allogeneic Autologous

High Risk for Azoospermia

Any alkylating agent + TBI, pelvic or testicular radiation

Testicular Cancer, SCT, ALL, NHL, sarcoma, Hodgkin, neuroblastoma

Any protocol with Procarbazine

Hodgkin Lymphoma

Cyclophosphamide 7.5gm/m2

Sarcoma, NHL, neuroblastoma, ALL

Cranial brain radiation >40 Gy

Brain Tumor

Intermediate Risk for Azoospermia

Bleomycin, Etoposide, Cisplatin

(BEP) X 2-4 cycles

Testicular Cancer

Cumulative Cisplatin dose <400 mg/m2

Testicular Cancer

Cumulative Carboplatin dose < 2 g/m2

Testicular Cancer

Intermediate Risk for Azoospermia

Testicular radiation dose 1-6 Gy

Due to scatter from abdominal/pelvic radiation

Wilm’s tumor and neuroblastoma

Low Risk for Azoospermia

Non-alkylating chemotherapy

ABVD, OEPA, NOVP, COP, CHOP

Hodgkin Lymphoma, Non-Hodgkin Lymphoma

Testicular radiation 0.2-0.7 Gy

Testicular Cancer

Very Low/No Risk for Azoospermia

Testicular radiation <0.2 Gy

Multiple Cancers

Interferon a Multiple Cancers

Radioactive Iodine Thyroid

Unknown Risk for Azoospermia

Irinotecan Bevacizumab (Avastin) Cetuximab (Erbitux) Erlotinib (Tarceva) Imatinib (Gleevec)

Preventative MeasuresPreventative Measures

Shielding during radiationShielding during radiation– Pre and post pubertal Pre and post pubertal

Hormonal manipulation (GnRH Hormonal manipulation (GnRH analogs) has not proven analogs) has not proven successful in gonadoprotectionsuccessful in gonadoprotection

Banking Options

Pre vs. Post Pubertal

Standard vs. Experimental

Banking Options: Post Banking Options: Post Pubertal MalePubertal Male StandardStandard

Sperm Banking:Sperm Banking:– Most effectiveMost effective– Obtained through masturbation then Obtained through masturbation then frozenfrozen

– Outpatient procedureOutpatient procedure– Success rate is generally highSuccess rate is generally high

Reports of 50% successful pregnancy Reports of 50% successful pregnancy raterate

– Potentially compromised sperm count Potentially compromised sperm count and increased risk of genetic damage and increased risk of genetic damage after a single treatmentafter a single treatment

Banking Options: Post Banking Options: Post Pubertal MalesPubertal Males

StandardStandard Sperm Banking ProcessSperm Banking Process

– MD/APN/PA orderMD/APN/PA order– Collection PRIOR to chemotherapy Collection PRIOR to chemotherapy and/or radiation is vitaland/or radiation is vital

– 2-3 samples are recommended2-3 samples are recommended– A sample can be provided every 24 A sample can be provided every 24 hours. hours.

– Collected in a sterile containerCollected in a sterile container At clinic location, hospital, homeAt clinic location, hospital, home Kept at body temperature and brought Kept at body temperature and brought to lab within one hourto lab within one hour

Sperm Banking Process Sperm Banking Process ContinuedContinued

Semen AnalysisSemen Analysis– Sperm count and movement Sperm count and movement – MorphologyMorphology– Semen is placed in individual Semen is placed in individual plastic vials for freezingplastic vials for freezing

CostCost– $125-$250 for analysis$125-$250 for analysis– $225-$375 for one year storage$225-$375 for one year storage

Mandatory Infectious Mandatory Infectious Disease TestingDisease Testing

Serum:Serum:– HIVHIV– Hepatitis A, B and CHepatitis A, B and C– RPR (Syphilis)RPR (Syphilis)– HTLV 1 and 2 (Human T-lymphotropic HTLV 1 and 2 (Human T-lymphotropic virus)virus)

– CMV IgG and IgMCMV IgG and IgM– Gonorrhea and Chlamydia (IgG and IgM)Gonorrhea and Chlamydia (IgG and IgM)– ASTAST

CostCost– Approximately $325Approximately $325

Banking Options: Post Banking Options: Post Pubertal MalesPubertal MalesExperimentalExperimental

ElectroejaculationElectroejaculation– Penile or RectalPenile or Rectal

Mechanical vibrator is placed at the Mechanical vibrator is placed at the base of the penis or in rectum and set base of the penis or in rectum and set to vibrate at a designated frequency to vibrate at a designated frequency and wave amplitude. and wave amplitude.

Vibration travels along the sensory Vibration travels along the sensory nerves to the spinal cord and may nerves to the spinal cord and may induce a reflex ejaculation. induce a reflex ejaculation.

– Approx 50 - 100% success rate of Approx 50 - 100% success rate of ejaculationejaculation

– Cost varies greatlyCost varies greatly

Banking Options: Post Banking Options: Post Pubertal MalesPubertal MalesExperimentalExperimental

Testicular sperm extraction– Outpatient procedureOutpatient procedure– Testicular mappingTesticular mapping– Success RateSuccess Rate

30-70% 30-70% 45% of azoospermic ejaculate after 45% of azoospermic ejaculate after cancer treatment cancer treatment

– Cost $4,000 - $16,000

Banking Options: Prepubertal Banking Options: Prepubertal MalesMales

Experimental OnlyExperimental Only Cryopreservation of testicular Cryopreservation of testicular tissue and stem cellstissue and stem cells– Tissue obtained via biopsy and Tissue obtained via biopsy and frozenfrozen

– In Vitro cultureIn Vitro culture Maturation of testicular stem Maturation of testicular stem cellscells

– Animal studies onlyAnimal studies only– AutotransplantationAutotransplantation

Risk of recurrence?Risk of recurrence?

Options after Cancer Treatment

Use of Frozen Sperm– In Vitro Fertilization (IVF)– Intra Cytoplasmic Sperm Injection Intra Cytoplasmic Sperm Injection ((ICSI)

Donor Sperm– $200 - 500 per vial

Adoption– $2,500 - $35,000

Options in Houston

Baylor College of Medicine – Urology

Medical Center

Houston IVF Memorial City

Advanced Fertility Center of Texas

Medical Center, Katy, Memorial City, Cy Fair, The Woodlands

Assessment of FertilityAfter Cancer Treatment

Semen analysis

Blood Work FSH Inhibin B

Cancer and InfertilityCancer and InfertilityWomenWomen

Cancer itself does not appear to affect fertility in women.

Cancer treatments pose spectrum of risk Immediate infertility Premature menopause Compromised ability to carry a pregnancy

Multifactoral process Drug type & dose Radiation location & dose Patient age & pubertal status Pre-treatment fertility

A Word About Prepubertal A Word About Prepubertal FemalesFemales

Early age at time of cancer Early age at time of cancer treatment has a protective treatment has a protective effecteffect– Younger age with larger number of Younger age with larger number of oocytes requiring more radiation oocytes requiring more radiation to cause damageto cause damage

– Less mitotic activityLess mitotic activity

Cancer and InfertilityCancer and InfertilityWomenWomen

Surgery can impair ability to become pregnant and/or carry pregnancy

Radiation can damage uterus and increase risk of miscarriage

Advise survivors who have received pelvic radiation should seek high-risk OB

Cancer and InfertilityCancer and InfertilityWomenWomen

Damage to oocytes and follicles can lead to immediate menopause or premature menopause years after treatment.

Menstruation does not equal fertility

Treatment affect on stromal function and ovarian blood vessels

High Risk >80% of women develop amenorrhea post-treatment

Whole abdominal or pelvic radiation doses> 6 Gy in adult women

Multiple cancers

Whole abdominal or pelvic radiation doses> 15 Gy in pre-pubertal girls> 10 Gy in post-pubertal girls

Wilms’ tumor, neuroblastoma,sarcoma, Hodgkin lymphoma

TBI radiation doses Stem cell transplant

CMF, CEF, CAF x 6 cycles in women 40 +

Breast cancer

Cyclophosphamide 5 g/m2 in women 40+

Multiple cancers

Cyclophosphamide 7.5 g/m2 in girls < 20

Non-Hodgkin lymphoma, neuroblastoma, ALL, sarcoma

High Risk >80% of women develop amenorrhea post-treatment

Alkylating chemotherapy(cyclophosphamide, busulfan, melphalan) conditioning for transplant

Stem cell transplant

Any alkylating agent (e.g.cyclophosphamide, ifosfamide, busulfan, BCNU,CCNU) + TBI or pelvic radiation

Stem cell transplant, ovarian cancer, sarcoma,neuroblastoma, Hodgkin lymphoma

Protocols containing procarbazine:MOPP, COPP, BEACOPP, MOPP/ABVD,COPP/ABVD

Hodgkin lymphoma

Cranial/brain radiation >40 Gy

Brain tumor

Intermediate Risk~30-70% of women develop amenorrhea post-treatment

CMF or CEF or CAF x 6 cycles in women 30-39

Breast cancer

Anthracycline & cyclophosphamide women 40 +

Breast cancer

Whole abdominal or pelvic radiation10-<15 Gy in prepubertal girls

Wilm’s tumor

Whole abdominal or pelvic radiation5-<10 Gy in postpubertal girls

Wilm’s tumor, neuroblastoma

Spinal radaition >25 Gy Spinal tumor, brain tumor, neuroblastoma, relapse ALL or NHL

Low Risk<20% of women develop amenorrhea post-treatment

AC (anthracycline, cytarabine)in women 30-39

Breast cancer

CMF, CEF or CAF x6 cycles in women 30-39

Breast cancer

Non-akylating chemotherapy: ABVD, CHOP, COP

Hodgkin lymphoma, NHL

AC AML

Multi-agent therapies ALL

Very Low RiskNegligible effect on menses

Methotrexate, 5 FU Breast cancer

Vincristine (used in multi-agent therapies)

Leukemia, NHL, Hodgkin lymphoma, neuroblastoma, rhabdomyosarcoma, Wilm’s tumor, Kaposi sarcoma

Radioactive Iodine Thyroid cancer

Unknown Risk

Paclitaxel, docetaxel Breast cancer

Oxaliplatin Ovarian cancer

Irinotecan Colon cancer

Bevacizumab (Avastin) Colon, non-small cell lung

Ceftuximab (Erbitux) Colon, head & neck

Trastuzamab (Herceptin)

Breast cancer

Erlotinib (Tarceva) Non-small cell lung, pancreatic

Imatinib (Gleevec) CML, GIST

Standard Female Reproductive Options

Embryo freezing Radiation shielding of ovaries Ovarian transposition Radical trachelectomy Donor embryos Donor eggs Gestational surrogacy Adoption

Embryo Freezing

Eggs are harvested and undergo in vitro fertilization. Embryos are frozen for later implantation.

Time requirement Cost: ~ $8,000-12,000 per cycle / ~ $8,000-12,000 per cycle / $350/year storage fees$350/year storage fees– Donor sperm $200-$500 / vialDonor sperm $200-$500 / vial

Success rate: 20-33%, babies born Special considerations: partner, donor sperm

Radiation Shielding of Ovaries

Shielding reduces scatter to reproductive options

Time requirement: non-issue Cost: included in cost of radiation

Success rate: limited to selected radiation fields

Special considerations: No protection from chemotherapy

Ovarian Transposition

Surgical repositioning of ovaries away from radiation field

Time requirement: Outpatient procedure

Cost: Maybe covered by insurance Success rate: Approximately 50% Special considerations: Expertise required

Radical Trachelectomy

Surgical removal of the cervix with preservation of uterus

Time requirement: During treatment Cost: Included in treatment cost Success rate: No evidence of higher recurrence rate

Special considerations: Early stage cervical cancer, limited centers

Standard Female Reproductive Options

Donor embryos– Not biologic child

Donor eggs– Offers opportunity for biologic child for father

Gestational surrogacy– Legal implications

Adoption– Inaccessibility to cancer survivors

Experimental Options

Egg/oocyte freezing Ovarian tissue preservation GnRH

Experimental Options for Experimental Options for FemalesFemales

Oocyte cryopreservation Oocyte cryopreservation

Process the same, sperm not neededProcess the same, sperm not needed Oocytes are more sensitive to Oocytes are more sensitive to freeze/thaw process and more prone to freeze/thaw process and more prone to damagedamage

Average 2% (range 1-5%) chance of Average 2% (range 1-5%) chance of pregnancy per oocyte (3-4 times less pregnancy per oocyte (3-4 times less than with embryo)than with embryo)

200+ live births to date200+ live births to date ~$12,000/cycle~$12,000/cycle

Experimental Options for Experimental Options for FemalesFemales

Ovarian Tissue cryopreservationOvarian Tissue cryopreservation Laparoscopic procedureLaparoscopic procedure Benefits:Benefits:

– Ovarian stimulation not performedOvarian stimulation not performed– Acquire hundreds of immature oocytesAcquire hundreds of immature oocytes– Less delay in commencement of cancer treatment Less delay in commencement of cancer treatment

HOWEVER – not a location available in Texas!HOWEVER – not a location available in Texas!

ConcernsConcerns– Reimplantation increase risk of recurrence?Reimplantation increase risk of recurrence?

How to develop the immature oocytes?How to develop the immature oocytes? Autotransplantation - Orthotopic vs. heterotopicAutotransplantation - Orthotopic vs. heterotopic XenotransplantationXenotransplantation

Two live births reported (2005)Two live births reported (2005) ~$12,000 for procedure; storage and reimplantation with ~$12,000 for procedure; storage and reimplantation with

additional costadditional cost Retrieval of immature oocytes with in vitro maturation (5 Retrieval of immature oocytes with in vitro maturation (5

y.o. youngest reported)y.o. youngest reported) Post chemotherapy preservation possible; however, lower Post chemotherapy preservation possible; however, lower

yieldyield

Assessment of Fertility

Difficult to predict reproductive horizon post treatment

Regaining menses post treatment does not imply intact fertility

Risk of premature ovarian failure is real

Current assessment is:– Day 3 of cycle

FSH LH Transvaginal ultrasound to assess antral follicle count

– AMH (anti-mullerian hormone): determine ovarian reserve

Experimental Options for Experimental Options for FemalesFemales

GnRH agonistGnRH agonist Lupron – 1 month or 3 month injectionLupron – 1 month or 3 month injection Creates a prepubertal state, suppressing ovulationCreates a prepubertal state, suppressing ovulation When to give?When to give?

– 2-3 weeks prior to chemotherapy to prevent breakthrough 2-3 weeks prior to chemotherapy to prevent breakthrough bleeding from occurring during time of cytopenia.bleeding from occurring during time of cytopenia.

– Give up to 2 doses or 6 months total – bone demineralizationGive up to 2 doses or 6 months total – bone demineralization What does the literature say?What does the literature say?

– Potential risks in hormone sensitive tumors unknownPotential risks in hormone sensitive tumors unknown– Does not protect follicles from radiationDoes not protect follicles from radiation– Mixed review Mixed review

No benefit vs. Menses resuming with or without pregnancy No benefit vs. Menses resuming with or without pregnancy achievementachievement– 98% vs. 40% resumption of menses 6 months post 98% vs. 40% resumption of menses 6 months post chemotherapychemotherapy

Do agree – decrease risks associated with menses during Do agree – decrease risks associated with menses during time of cytopeniatime of cytopenia

Window of opportunity Window of opportunity Cost - $500/monthCost - $500/month

Options in Houston

Embryo freezing- Fertile Hope referrals

Radiation shielding- Radiation Oncologist

Ovarian transposition- Surgery Radical Trachelectomy- MDACC, Pedro Ramirez, MD

Exploring option with Baylor group for ovarian tissue preservation

Potential Barriers for Men and Women

Lack of information of treating oncologist

Lack of referral network Perceived financial burden to families

Facility not adolescent friendlyFacility not adolescent friendly TimeTime Parental anxietyParental anxiety Spiritual concernsSpiritual concerns

Resources

Fertility Consult Service– Anna Franklin, MD– Donna Herrera-Bell– Nicole Rosipal, RN, MSN, CPNP

Services Provided– Discussion of infertility risk and available options

– Referral Process

– Consult Request– Wednesday, Thursday and Friday afternoons

ResourcesResources

LIVELIVESTRONGSTRONG Survivor Care Survivor Care– www.LIVESTRONG.org/survivorcare– Information about fertility preservation, Information about fertility preservation, financial, insurance and employment concernsfinancial, insurance and employment concerns

– LIVE:ONLIVE:ON Fertile HopeFertile Hope

– www.fertilehope.org– Sharing Hope programSharing Hope program– Self referralSelf referral

Oncofertility ConsortiumOncofertility Consortium Heroes for children – up to 22 Heroes for children – up to 22

– http://www.heroesforchildren.org/– Social worker completes assessment and application Social worker completes assessment and application – Assistance is based on financial need ($750 Assistance is based on financial need ($750 towards expenses)towards expenses)

Current Research at MD Anderson

Banking on Fatherhood

St. Jude’s Questionnaire– Attitude about sperm banking

Discussion

ReferencesReferences Biro, F. M., et al. (2010) Normal Puberty. Up to Date. Biro, F. M., et al. (2010) Normal Puberty. Up to Date.

www.uptodate.com Blumenfeld, Z. (2008). GnRH-agoinst in fertility Blumenfeld, Z. (2008). GnRH-agoinst in fertility

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Lee, S. J., Schover, L. R., Partridge, A. H., Patrizio, P., Lee, S. J., Schover, L. R., Partridge, A. H., Patrizio, P., Wallace, W. H., Hagerty, K., et al. (2006). American Society Wallace, W. H., Hagerty, K., et al. (2006). American Society of Clinical Oncology recommendations on fertility of Clinical Oncology recommendations on fertility preservation in cancer patients. preservation in cancer patients. J Clin Oncol, 24J Clin Oncol, 24(18), 2917-(18), 2917-2931.2931.

References References Neal, M. S., Nagel, K., Duckworth, J., Bissessar, H., Fischer, M. Neal, M. S., Nagel, K., Duckworth, J., Bissessar, H., Fischer, M.

A., Portwine, C., et al. (2007). Effectiveness of sperm banking in A., Portwine, C., et al. (2007). Effectiveness of sperm banking in adolescents and young adults with cancer: a regional experience. adolescents and young adults with cancer: a regional experience. Cancer, 110Cancer, 110(5), 1125-1129.(5), 1125-1129.

Author, A. A., & Author, B. B. (Year of publication). Late effects Author, A. A., & Author, B. B. (Year of publication). Late effects of childhood cancer and its treatment. In Pizzo, P. A. & Poplack, of childhood cancer and its treatment. In Pizzo, P. A. & Poplack, D.G. (Eds.), D.G. (Eds.), Prinicples and Practices of Pediatric OncologyPrinicples and Practices of Pediatric Oncology (1503- (1503-06). Philadelphia, PA: Lippincott Williams & Wilkins.06). Philadelphia, PA: Lippincott Williams & Wilkins.

Revel, A., Revel-Vilk, S., Aizenman, E., Porat-Katz, A., Safran, A., Revel, A., Revel-Vilk, S., Aizenman, E., Porat-Katz, A., Safran, A., Ben-Meir, A., et al. (2009). At what age can human oocytes be Ben-Meir, A., et al. (2009). At what age can human oocytes be obtained? obtained? Fertil Steril, 92Fertil Steril, 92(2), 458-463.(2), 458-463.

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the role of the pediatric nurse practitioner in fertility the role of the pediatric nurse practitioner in fertility preservation. preservation. J Pediatr Oncol Nurs, 26J Pediatr Oncol Nurs, 26(1), 48-59.(1), 48-59.