Fertility issues for patients with lymphoma

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

2. 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

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 – 276 6473 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. 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 Ovarian storage

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

24. Risks High circulating oestradiol Delay to treatment Need for partner (embryos) Risk that partner will “change mind” (embryos) Benefits Successful Proven method Proven safety Egg and embryo cryopreservation

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