cheryl fitzgerald dept of reproductive medicine st mary’s hospital manchester fertility issues for...
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Cheryl FitzgeraldDept of Reproductive Medicine
St Mary’s HospitalManchester
Fertility issues for patients with lymphoma
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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 treatmentLong 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
VitrificationSlow 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• <35 years 32.8%• 35-37 years 27.3%• 38-39 years 19.0%• 40-42 years 11.8%• 43-44 years 4.8%• >44 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 < 40 years– Stable cohabitation >2 years– One partner childless– Only couples treated– Female BMI< 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