1

Fertility preservation in cancer patients: practices

from the experts and from WH Summit delegates

Prof. Milton Leong, MD

Prof. Zeev Shoham

IVF-Worldwide.com

2

Fertility preservation: …. Why?

• Increase incidence of cancer during the reproductive age

• Survival and cure rates of cancer are improving

• One of 1000 adults is a survivor of childhood cancer

• Technology is improving!

Rebecca Siegel, Jiemin Ma, Zhaohui Zou, and Ahmedin Jemal. Cancer statistics, 2014.

3

Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer

Joseph M. Letourneau MD, Erin E. Ebbel BA, Patricia P. Katz PhD, Audra Katz RN, Wei Z. Ai D, A. Jo Chien MD, Michelle E. Melisko MD, Marcelle I. Cedars MD, Mitchell P. Rosen MD Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco School of Medicine, San Francisco, California

Cancer 2011

Receiving specialized counseling about reproductive loss and pursuing fertility preservation is associated with greater QOL for survivors

4

The patient pathway

Develop treatment plan

Yes No

Assess fertility risk diagnosis

Diagnosis Develop

treatment plan Assess fertility

risk

Discuss impact of cancer and treatment

on reproductive health

Patient interested in

fertility preservation?

Refer to reproductive

specialist

Discuss fertility

preservation options

Pursue fertility

preservation option

Proceed with treatment

5

6

7

8

• Preimplantation genetic screening: results of a worldwide web-based survey.

• Weissman A, Shoham G, Shoham Z, Fishel S, Leong M, Yaron Y. Reprod Biomed Online. 2017;21:1472-6483.

• Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey. Christianson MS, Shoham G, Tobler KJ, Zhao Y, Monseur B, Leong M, Shoham Z. J Assist Reprod Genet. 2017;34(8):1059-1066.

• Chromosomal mosaicism detected during preimplantation genetic screening: results of a worldwide Web-based survey. Weissman A, Shoham G, Shoham Z, Fishel S, Leong M, Yaron Y. Fertil Steril. 2017;107(5):1092-1097.

• Minimizing the Risk of Infection and Bleeding at Trans-Vaginal Ultrasound-Guided Ovum Pick-up: Results of a Prospective Web-Based World-Wide Survey. J Obstet Gynaecol India. 2015 ;65(6):389-95.

• Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide. J Assist Reprod Genet. 2015 ;32(10):1441-8. • Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey. J Assist Reprod Genet. 2015

;32(10):1435-40. • How to define, diagnose and treat poor responders? Responses from a worldwide survey of IVF clinics Reprod Biomed Online. 2015 Jun;30(6):581-92 • Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey J Assist Reprod Genet. 2015 • Embryo catheter loading and embryo culture techniques: results of a worldwide web-based survey Journal of Assisted Reproduction and Genetics, 2014:8;1029-

36 • Luteal phase support in ART treatments Human Fertility, Methods in Molecular Biology Volume 1154, 2014, pp 251-260 • Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques Archives of Gynecology and Obstetrics, September 2014:290;561-568 • Characterizing the practice of oocyte donation: a web-based international survey Reproductive BioMedicine Online, 2014:4;443–450 • Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey Reproductive BioMedicine

Online, 2014:28:443–450 • Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection

treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles Fertility and Sterility, 2014:101;105–111 • Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com Journal of Assisted Reproduction and Genetics

2013:30;1169-1174 • How to recognize PCOS: results of a web-based survey at IVF-worldwide.com Reproductive BioMedicine Online 2013:26;500–505 • Current trends of reproductive immunology practices in in vitro fertilization (IVF) - a first world survey using IVF-Worldwide.com American Journal of

Reproductive Immunology 2013:69;12–20

IVF providers Hemato-oncologists

Support by Teva Pharmaceuticals

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Survey participants

Continent IVF units % Oncologists %

USA & Canada 53 17.1 13 9.85

South America 39 12.58 3 2.27

Australia & New Zealand 13 4.19 3 2.27

Asia 58 18.71 17 12.88

Europe 138 44.52 94 71.21

Africa 9 2.9 2 1.52

TOTAL 310 100 132 100

Corresponding to 517,600 cycles

Do you perform treatment for fertility preservation for cancer patients or do you refer patients to other treatment centers?

We perform the treatment We refer the patient to other centersWe do not have fertility preservation

patients

unit 86 9.3 4.7

cycle 87.6 6.7 5.8

0

10

20

30

40

50

60

70

80

90

100

unit

cycle

12

Q2: Cancer patients who consult for fertility preservation:

74

19

7

0

10

20

30

40

50

60

70

80

Are referred mostly byoncologists

Are not referred byoncologists: they seek advice

on their own

Our unit does not treatoncofertility patient

IVF specialists

12

13

Statement: Fertility preservation is a high priority for me to discuss with newly diagnosed cancer patients

13

94

5 1

70

24

5

0

10

20

30

40

50

60

70

80

90

100

Agree Neither agree nor disagree Disagree

%

IVF specialists Hemato-oncologists

14

Q3: Does the oncologist sufficiently address / inform patients about fertility after cancer treatment?

14

In case of risk of infertility do you inform your patients?

Hemato-oncologists IVF specialists

24

63

13

0

10

20

30

40

50

60

70

80

90

Yes No Do not know

%

86

11

2 0

10

20

30

40

50

60

70

80

90

Yes, I do Yes by my team I leave it to the IVFteam

15

Q4: To your opinion, is there any age limit to the fertility preservation procedure?

15

16

9

25

32

19

23

14 16

26

22

0

5

10

15

20

25

30

35

None Up to 35 Up to 37 Up to 40 Up to 42

%

Hemato-oncologists IVF specialists

Age, years

16 16

Of your young female cancer patients (≤ 40 years old) who underwent treatment that may have adversely affected their future fertility, what is the percentage who actually benefited from a fertility preservation procedure?

6 3

12 10

17 17

35

0

5

10

15

20

25

30

35

40

More than 70% 50% to 70% 40% 30% 10% to 20% 5% to 10% Less than 5%

%

Hemato-oncologists

17

Q5: Who typically pays for fertility preservation treatment for cancer patients?

17

60

27

8 5

30

51

10 10

0

10

20

30

40

50

60

70

Patient of family Government/Socialsecurity program

Insurance Others or don't know

%

Hemato-oncologists IVF specialists

18

Q6: In patients with malignant hematological diseases, when do you start fertility preservation treatment?

18

72

14

3

12

0

10

20

30

40

50

60

70

80

Immediately Wait for the foll phase Start in the lutealphase

Our unit does treatoncofertility patients

%

IVF specialists

19

Q7: In the case in which you use a GnRH antagonist protocol for fertility preservation in cancer patients, do you trigger with an agonist?

19

74

15

2

9

0

10

20

30

40

50

60

70

80

Yes No Our unit does useGnRH antagonist

Our unit does treatoncofertility

patients

%

IVF specialists

20

6

16

34 37

8

0

5

10

15

20

25

30

35

40

3-5 6-10 11-15 More than 15 I don't haveexperience in

this field

%

20

Q8: How many cryopreserved oocytes would be sufficient for you to recommend that further treatment cycles are not necessary?

IVF specialists

>11

21

Q9: Statement - Cryopreservation of ovarian tissue is still an experimental procedure

21

53

21

26

0

10

20

30

40

50

60

Yes Neither agree nor disagree Disagree

%

IVF specialists

22

Q10: Statement -The success rate of fertility preservation is not yet good enough to make it an available option.

22

9 14

77

24 28

48

0

10

20

30

40

50

60

70

80

90

Agree Neither agree nor disagree Disagree

%

IVF specialists Hemato-oncologists

23

Q11: Were there pregnancies in your center in the following situations? (multiple answers allowed)

23

IVF specialists

57

36

10

18 17

0

10

20

30

40

50

60

%

No pregnancies I am not aware of

any pregnancies

From transplanted ovaries

From cryopreserved

oocytes

From frozen embryos

24

Q12: The pregnancy rate after oocyte cryopreservation in cancer patients is not yet known because

24

IVF specialists

44

4

43

9

0

5

10

15

20

25

30

35

40

45

50

%

Not enough patients

Oocytes ability to be fertilized is impaired

There is no proper registry

Other reasons

25

Q13: Statement - Treating the primary cancer is more important than fertility preservation

25

46

34

20

53

36

11

0

10

20

30

40

50

60

Agree Neither agree nor disagree Disagree

%

IVF specialists Hemato-oncologists

26

Q14: Do you think that hormonal treatment for fertility preservation can aggravate the malignant disease?

26

11

61

28

0

10

20

30

40

50

60

70

Yes No I don’t know

%

Hemato-oncologists

27

Q15: In your country, are there any local/national guidelines on fertility preservation for cancer patients?

27

43

52

5

31

48

20

0

10

20

30

40

50

60

Yes No I don't know

%

IVF specialists Hemato-oncologists

28

Q16: Statement - National guidelines on fertility preservation for cancer patients are useful/needed

28

89

7 4

92

6 2

0

10

20

30

40

50

60

70

80

90

100

Yes No Disagree

%

IVF specialists Hemato-oncologists

29

Conclusions of the existing survey

• In general, IVF units are comfortable with the cryopreservation techniques

• Physicians would appreciate guidelines and standardization.

• Education would be much appreciated.

• The gynecologists think that the oncologists should be more aware to fertility preservation.

• We are offering the option but the results are not yet known.

• Bias of survey – answered by units performing the procedure

29