Cheryl Fitzgerald

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Fertility issues for patients with lymphoma

• Cheryl Fitzgerald
• Dept of Reproductive Medicine
• St Marys Hospital
• Manchester

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Issues to consider

• Two diagnoses
• Malignancy and infertility
• Counselling
• Delay in conception
• Marked decline in female fertility 35 onwards
• Effect of disease/treatment
• Spermatogenesis
• Ovary oocytes
• Uterus radiotherapy induced damage

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Issues affecting fertility

• Delay in conception female
• Disease
• Surgery
• Chemotherapy
• Radiotherapy
• Long term prognosis Welfare of Child

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• Male
• Options - easy

• Female
• Options complex

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Men

• Men and postpubertal boys
• Need to screen for Hep B, Hep C and HIV
• Urgent direct referral
• Phone Andrology SMH 276 6473
• Produce single (?more) sample
• Frozen in several ampoules
• Stored for up to 55 years
• Sperm used for insemination or IVF

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Options for treatment with cryopreserved sperm

• Sperm quality good use for insemination
• Sperm quality poor use for IVF
• Treatment within NHS dependent upon NHS assisted
  conception guidelines
• Sperm can be transferred to private sector is not
  eligible

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Delay in conception - females

• Initial treatment
• Long term therapy (breast)
• Time until cure
• Age related decline in female fecundity
• Age related decline in ovarian reserve
• Increase in oocyte aneuploidy
• Marked reduction 35 onwards

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Effects of chemotherapy

• Damage to primordial follicles
• Damage to primary follicles
• Oogenesis many months
• May be temporary disruption
• No benefit from GnRH agonist treatment
• No effect on uterus

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Risk factors for iatrogenic POF

• Older women poor ovarian reserve
• Dose, type and duration of chemotherapy
• Pelvic radiotherapy / TBI

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Effects of radiotherapy

• Site specific
• Pelvic radiotherapy / TBI
• profound oocyte damage
• profound uterine damage
• Oocyte damage
• Premature ovarian failure
• Uterine damage
• Poor implantation rates after XRT
• Poor pregnancy outcome after XRT

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Fertility preservation options pre-treatment

• Cryoprserve ovarian tissue
• Cryopreserve oocytes
• Cryopreserve embryos
• Consider uterine function

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Ovarian cryopreservation

• Laparoscopic oophorectomy
• Ovarian cortex frozen in strips
• Later replace ovarian tissue within pelvis
• Spontaneous/stimulated ovarian cycle
• ?? In vitro maturation in the future
• 10 (2) babies worldwide
• No time limit on storage

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Ovarian storage

• Risks
• Very low success rates
• Risk of laparoscopy
• Risk of re-introducing disease

• Benefits
• No need for hyperstimulation
• No raised oestradiol level
• No need for partner
• Minimal delay in treatment

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Who is suitable?

• Lymphoma patients
• Very young girls ?? Prepubertal
• No metastatic disease in ovaries
• Limited time

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Primordial follicle grafting

• Stored ovarian tissue
• Primordial follicles grafted into mice
• No need to transplant tissue

Ref. Brison et al Not published
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Egg and embryo freezing

• Need to retrieve mature eggs from ovaries
• No stimulation single egg poor success
• Need for ovarian hyperstimulation

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Ovarian hyperstimulation cycle

• 10 days of ovarian stimulation starts with
  period
• NB delay caused by waiting for menses
• Vaginal egg recovery
• Ostradiol raised through stimulation

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Oocyte cryopreservation

• problematic
• chromosomes on spindle
• aneuploidy after thaw
• zona pellucida and cortical
• granule damage
• affect fertilisation
• need for ICSI

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Oocyte cryopreservation

• Freeze all mature eggs recovered
• Can be stored for 55 years
• HFEA Code of Practice 8
• No reduction in quality of eggs with increasing
  time

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Oocyte cryopreservation - progress

• Improving vitrification
• Rapid cooling without crystal formation
• Vitrification Slow freeze
• Survival 80 60
• Fertilisation 75 65
• Pregnancy 9 4

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Safety of egg freezing

• 936 babies
• Birth anomalies 1.3
• No difference compared to spontaneously conceived
  children
• Noyes et al 2009

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Embryo cryopreservation

• need a partner
• urgent IVF
• minimum time 4-6 weeks
• ovarian hyperstimulation
• oocyte recovery
• eggs inseminated
• embryos created frozen

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Risks associated with urgent IVF for egg or
embryo cryopreservation

• high circulating oestradiol (20 000 cf 500
  pmol/l)
• issue with Ca breast
• potential seeding of gynae malignancies
• delay in cancer treatment

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Egg and embryo cryopreservation

• Risks
• High circulating oestradiol
• Delay to treatment
• Need for partner (embryos)
• Risk that partner will change mind (embryos)

• Benefits
• Successful
• Proven method
• Proven safety

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Chance of baby embryo freeze

• HFEA data livebirth per fresh cycle 2008
• lt35 years 32.8
• 35-37 years 27.3
• 38-39 years 19.0
• 40-42 years 11.8
• 43-44 years 4.8
• gt44 years 3.8
• 30 embryo loss with freezing

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Embryo freezing

• Freeze all embryos created at pronucleate stage
• Can be stored for 55 years
• No reduction in quality of embryos with
  increased time in storage

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Practicalities

• Urgency referral early
• Fax referral and confirm by phone
• Cycle control COCP limits delay
• Details
• Timing of chemo
• Need for pelvic radiotherapy
• Longterm therapies
• Prognosis

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After treatment

• Referred as any infertility patient

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Egg donation

• Donor IVF stimulation
• Partner sperm for insemination
• Embryo(s) replaced in recipient
• HRT support to 12 weeks of pregnancy
• Success rates 30-50
• Right of child to access donor information

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Surrogacy

• After hysterectomy / pelvic radiotherapy
• Problematic
• No legal contract
• Surrogate legal mother

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Eligibility IVF in NHS

• NHS IVF guidelines
• Female lt 40 years
• Stable cohabitation gt2 years
• One partner childless
• Only couples treated
• Female BMIlt 30
• No previous sterilisation

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Fertility preservation eligibility - NHS

• Female age ?
• Cohabitation - ?
• One partner childless
• Single women treated
• BMI ?
• No previous sterilisation
• NB PCT funding needs agreement

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Welfare of the Child

• Legal requirement
• HFEA Act
• Prognosis for patient important
• Partner / family support

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Thank-you