Fertility issues for patients
with lymphoma
Cheryl Fitzgerald
Dept of Reproductive Medicine
St Mary’s Hospital
Manchester
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
Issues affecting fertility
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Delay in conception – female
Disease
Surgery
Chemotherapy
Radiotherapy
Long term prognosis – Welfare of Child
• Male
• Female
• Options - easy
• Options complex
Men
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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
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
Delay in conception - females
Initial treatment
Long term therapy (breast)
Time until “cure”
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Age related decline in female fecundity
Age related decline in ovarian reserve
Increase in oocyte aneuploidy
Marked reduction 35 onwards
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
Risk factors for iatrogenic POF
• Older women – poor ovarian reserve
• Dose, type and duration of chemotherapy
• Pelvic radiotherapy / TBI
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
Fertility preservation options –
pre-treatment
• Cryoprserve ovarian tissue
• Cryopreserve oocytes
• Cryopreserve embryos
• Consider uterine function
Ovarian cryopreservation
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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
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
Who is suitable?
Lymphoma patients
Very young girls ?? Prepubertal
No metastatic disease in ovaries
Limited time
Primordial follicle grafting
• Stored ovarian tissue
• Primordial follicles grafted into mice
• No need to transplant tissue
Ref. Brison et al
Not published
Egg and embryo freezing
• Need to retrieve mature eggs from ovaries
• No stimulation – single egg – poor
success
• Need for ovarian hyperstimulation
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
Oocyte cryopreservation
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problematic
chromosomes on spindle
aneuploidy after thaw
zona pellucida and cortical
granule damage
affect fertilisation
• need for ICSI
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
Oocyte cryopreservation - progress
• Improving ++ vitrification
• Rapid cooling without crystal formation
• Survival
• Fertilisation
• Pregnancy
Vitrification
Slow freeze
80%
75%
9%
60%
65%
4%
Safety of egg freezing
• 936 babies
• Birth anomalies – 1.3%
• No difference compared to spontaneously
conceived children
• Noyes et al 2009
Embryo cryopreservation
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need a partner
“urgent” IVF
minimum time 4-6 weeks
ovarian hyperstimulation
oocyte recovery
eggs inseminated
embryos created frozen
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
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
Chance of baby – embryo freeze
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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
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
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
After treatment
• Referred as any infertility patient
Egg donation
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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
Surrogacy
• After hysterectomy / pelvic radiotherapy
• Problematic +++
• No legal contract
• Surrogate – legal mother
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
Fertility preservation eligibility NHS
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Female age ?
Cohabitation - ?
One partner childless
Single women treated
BMI ?
No previous sterilisation
• NB – PCT funding – needs agreement
Welfare of the Child
• Legal requirement
• HFEA Act
• Prognosis for patient important
• Partner / family support
Thank-you