Fertility Preservation Women

Julia Kopeika MRCOG, PhD

Consultant GynaecologistSubspecialist in Reproductive Medicine

11th October 2019

Content1) Why Fertility Preservation (FP)2) Options for fertility preservation 3) How does Controlled Ovarian Stimulation (COS)

work and timeline4) Risks associated with COS5) Eggs or Embryos? 6) UK National experience7) Take home message

Why Fertility Preservation?² Increasing survival rate of cancer patients

² Importance in the quality of life after cancer and chemotherapy

² Increasing age of having a first child

² New more efficient reproductive techniques

Options for Fertility Preservation

1. Cryopreservation of Oocytes (eggs)

2. Cryopreservation of Embryos

3. Cryopreservation of Ovarian Tissues (no national funding yet)

4. Medical protection with gonadotropin-releasing hormone Agonist (GnRHa)

LH hCG/GnRHa

Follicle-stimulating hormone (FSH) in natural cycle

FSH during COS/IVF

2 weeks 1) Potential for multiple eggs / cycle by Extending “FSH window”2) Prevention of Luteinising hormone (LH) surge and spontaneous ovulation3)Trigger of timed artificial LH surge with surrogate molecules= Human

chorionic gonadotropin (hCG) or GnRHa

FSH concentration

Basic Principals of Controlled Ovarian Stimulation

Transvaginal egg collection

Timeline

Referrals Patient Evening

1st Consult Tx (IVF/ICSI)

Funding

6 – 8 weeks

Fertility Treatment

Fertility Preservation

4.1±2.1 2±14 10±2.52 - 3 weeks

Risks Associated with COS

1. Ovarian Hyperstimulation Syndrome (OHSS)ascites, hypercoagulation, increased risk of VTE,liver and kidney dysfunction

GnRH agonist vs hCG

Cochrane Review 2014 Youssef et al

Risks Associated with COS

1. Ovarian Hyperstimulation Syndrome (OHSS)ascites, hypercoagulation, increased risk of VTE,liver and kidney dysfunction

2. No or poor response, no eggs/no embryos3. Cancer specific risks4. Long term safety (cancer recurrence/survival) and

efficacy

Risks Associated with COS

1. Ovarian Hyperstimulation Syndrome (OHSS)ascites, hypercoagulation, increased risk of VTE,liver and kidney dysfunction

2. No or poor response, no eggs/no embryos3. Cancer specific risks4. Long term safety (cancer recurrence/survival) and

efficacy

Cancer Type Potential considerationsEr+ Breast cancer Risk for Ca

(currently empirical use of tamoxifen/letrozole during COS)

Lymphomas Assess if they have a large mediastinal mass –anesthetics concerns/review

Myelodysplastic disease low platelets (<50) risk of bleeding

Thrombocytosis, malignancy

Risk of thrombosis during COS, thromboprophylaxis? When and how much

Cervical Ca, Colon/Rectal Surgical risks?/spread during Egg retrievalEffect of future treatment on capability to carry a baby (may need surrogacy)

Risks Associated with COS

1. Ovarian Hyperstimulation Syndrome (OHSS)ascites, hypercoagulation, increased risk of VTE,liver and kidney dysfunction

2. No or poor response, no eggs/no embryos3. Cancer specific risks4. Long term safety (cancer recurrence/survival) and

efficacy

Cancer Type Potential considerations

Brain tumors recent radiotherapy/surgeryEpilepsy – anaesthetics assessment, response to GnRH agonist as a trigger

Young peri-pubertal patients Response to stimulation (may have lower than expected), assessment of response/ access to the ovaries?

Genetics pre-disposition (Lynch, BRCA, NF)

Place of Preimplantation Genetics Diagnostics (PGD), inheritance

Long Term Safety

Survival and recurrence was assessed and reported in 149 women with breast cancer. Recurrence rate was

5% over mean period of 5 years

Long Term EfficacyEggs or Embryos?

Ex ovo omnia – all things come from the egg

Cryopreservation and IVF

1978

First IVF babyborn

1983 1984

Slow freezing Human embryo

Vitrification

1986

First Baby fromfrozen oocyte (Slow

Freezing)

1992 1996

ICSI

Ovarian TissuePreservation

First Baby fromfrozen embryo

1985 1999

First Baby fromVitrified Oocyte

HFEA report 2018

22 % 19 %

What is better Eggs or Embryos?

Anything else to consider????

Ovarian Tissue Preservation“Cryopreservation of ovarian and testicular tissue is largelyundertaken in a research Setting.”NICE 2013

“Ovarian tissue cryopreservationis an option to preserve reproductive potential……. And may be the only option available to prepubertal girls undergoing such treatments. However, these techniques are still considered to be experimental. “ASRM 2015

B

Medical protection with GnRHa

Clinical evidence on GnRHa protectionBreast Cancer Studies Lymphomas Studies

Studies 14 RCT 4 RCT

Sample size 100 (1647 in total) 30 and under (154 in total)

Age (median) 40 y.o 25 y.o

Assessed Outcome Amenorrhea or FSH/LH (only 1 study looked at pregnancy

Amenorrhea or FSH/LH, AMH(1 looked at pregnancy)

Type of chemo Intermediate risk of gonadotoxicity

Low and high-risk of gonadotoxicity

Duration of follow up 6 month to 5 years 6 month to 5-7 years

Conclusion All but 4 showed benefits ↓ POI

None showed protective effect

From analysis done by Lambertini et al, 2019

What’s happening nationally?21 997 cases per year in women aged 25-4911 166 cases per year in men aged 25-491135 boys1097 girls

Total: 35 395Estimated number of patients to whom FP

could be recommended 5000?

Take home message1. Don’t assume patient fertility intention (even if

they have already a child)2. Don’t refer patients with poor prognosis of

survival 3. Offer consultation regarding fertility and leave

discussion about funding to us 4. Remember to advice on contraception, even if no

periods5. Refer patients as early as possible6. Know your local service providers and pathways

Any questions?

yuliya.kopeika@gstt.nhs.uk

ivf.fertilitypreservation@gstt.nhs.uk