1. Fertility issues for patients with lymphoma
Cheryl Fitzgerald
Dept of Reproductive Medicine
St Mary’s Hospital
Manchester

2. Issues to consider Two diagnoses Delay in conception
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

3. Issues affecting fertility
Delay in conception – female
Disease
Surgery
Chemotherapy
Radiotherapy
Long term prognosis – Welfare of Child

4. Male
Options - easy
Female
Options complex

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

6. 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

7. 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

8. 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

9. Risk factors for iatrogenic POF
Older women – poor ovarian reserve
Dose, type and duration of chemotherapy
Pelvic radiotherapy / TBI

10. 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

11. Fertility preservation options – pre-treatment
Cryoprserve ovarian tissue
Cryopreserve oocytes
Cryopreserve embryos
Consider uterine function

12. 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

13. 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

14. Who is suitable? Lymphoma patients Very young girls ?? Prepubertal
No metastatic disease in ovaries
Limited time

15. Primordial follicle grafting
Stored ovarian tissue
Primordial follicles grafted into mice
No need to transplant tissue
Ref. Brison et al
Not published

16. Egg and embryo freezing
Need to retrieve mature eggs from ovaries
No stimulation – single egg – poor success
Need for ovarian hyperstimulation

17. 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

18. Oocyte cryopreservation
problematic
chromosomes on spindle
aneuploidy after thaw
zona pellucida and cortical
granule damage
affect fertilisation
need for ICSI

19. 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

20. Oocyte cryopreservation - progress
Improving ++ vitrification
Rapid cooling without crystal formation
Vitrification Slow freeze
Survival 80% 60%
Fertilisation 75% 65%
Pregnancy 9% 4%

21. Safety of egg freezing 936 babies Birth anomalies – 1.3%
No difference compared to spontaneously conceived children
Noyes et al 2009

22. Embryo cryopreservation
need a partner
“urgent” IVF
minimum time 4-6 weeks
ovarian hyperstimulation
oocyte recovery
eggs inseminated
embryos created frozen

23. Risks associated with “urgent” IVF for egg or embryo cryopreservation
high circulating oestradiol ( cf 500 pmol/l)
issue with Ca breast
potential seeding of gynae malignancies
delay in cancer treatment

24. 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

25. 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

26. 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

27. 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

28. After treatment
Referred as any infertility patient

29. 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

30. Surrogacy After hysterectomy / pelvic radiotherapy Problematic +++
No legal contract
Surrogate – legal mother

31. 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

32. Fertility preservation eligibility - NHS
Female age ?
Cohabitation - ?
One partner childless
Single women treated
BMI ?
No previous sterilisation
NB – PCT funding – needs agreement

33. Welfare of the Child Legal requirement HFEA Act
Prognosis for patient important
Partner / family support

34. Thank-you