fertility preservation for the woman with cancer€¦ · breast cancer hl nhl leukemia ewing...

Prof. Antonio Pellicer

[email protected]

www.ivi.es

FERTILITY PRESERVATION FOR THE WOMAN WITH CANCER

IntroductionIntroduction

SEER and EUROCARE registries

IntroductionIntroduction

• Breast cancer:

– The most common malignancy in women at reproductive age

– 6.4% <40 yrs at diagnosis

Fertility preservation in women with cancerFertility preservation in women with cancer

•Medical protection of the gonads

•Ovarian cortex freezing/transplantation

•Oocyte/embryo vitrification





Medical Gonadal ProtectionMedical Gonadal Protection

Del Mastro et al. JAMA 2011; 306: 269-276


Del Mastro et al. JAMA 2011; 306: 269-276


Del Mastro et al. Cancer Treat Rev. 2014; 40:675-683

Premature Ovarian Failure


Moore et al. NEJM. 2015; 923

Ovarian Failure: 8% in Goserelin group and 22% in the chemotherapy-alone group (P=0.04)


Moore et al. NEJM. 2015; 923

Overall Survival Rates

AMH Physiology


Hasky et al. Hum Reprod. 2015; 30: 1089


Hasky et al. Hum Reprod. 2015; 30: 1089





PÁG.15

MEAN AGE 29 yrs (range 11-39 yrs)

Previous CHT: YES 15%; NO 85%

N= 717

Transplantations=33(June, 2015)

Ovarian cortex Orthotrasplantation program (Established 2005)

Breast Ca 55% Hodgkin 21% Others 24%

Trasplante ortotópico de ovario

PÁG.16

Orthotopic ovarian grafting

Entire ovary Cortical strips

Orthotopic Ovarian GraftingOrthotopic Ovarian Grafting

Schmidt K et al. RBMOnline 2013; 26: 272-9

The need ovarian grafting after treatment

- Questionnaire about spontaneous menstrual cycles and pregnancies


The need ovarian grafting after treatment

Diaz C, (Unpublished)

Donnez et al Ann. Med. 2011; doi: 10.3109/07853890.2010.546807


Initiation of graft function


Greve et al. Fertil Steril. 2011

Duration of graft function

References * Cryopreservation

procedureLive births

Spont IVF N

Donnez et al., 2004, 2010, 2011, 2012, 2013, 2014

SF +

+++

++

6

Meirow et al., 2005, 2012 SF + +++ 4

Demeestere et al., 2007 SF ++ - 2

Andersen et al., 2008, 2009, 2011, Schmidt, 2012, 2013, 2014

SF ++ ++

+ +

6

Silber et al., 2008, 2010 SF + +

- 2

Piver et al., 2009 Roux et al, 2010

SF + +

- 2

Sanchez et al., 2009 Pellicer et al., 2013**

SF ++ ++ (twins) 4

Revel et al., 2010, 2012 SF - + +

2

Dittrich et al., 2012, 2014 SF +++ + 4

Revelli et al., 2013 SF + 1

Callejo et al., 2013 SF + 1

Stern et al., 2013*** SF ++ 2

Kawamura, 2013 VF + 1

Live births after transplantation of frozen thawed ovariancortex

Donnez et al, The Lancet, 2015

Teams Number of

transplanted women

Women who

conceived

Women who

gave birth

Number of live

births

Miscarriages

Donnez, Dolmans

team

13 3 3 6*

**

Andersen, Macklon

team

25 6 4 6*

**

2

Pellicer team 22 4 3 4 1

Dittrich team 20 7 4 (+2***) 4 (+2***) 1

80 20 (25%) 14 20

*One woman delivered twice**One woman delivered three times

***Two ongoing pregnanciesDonnez et al, The Lancet, 2015

Live births after transplantation of frozen thawed ovariancortex

Meirow D et al. Hum Reprod. 2008

Sánchez-Serrano M et al. Hum Reprod. 2009

Dolmans et al. Blood 2010

Greve et al. Blood 2012

Abir R et al. Hum Reprod 2010

DISEASE SAFE UNSAFE

BREAST CANCER

HL

NHL

LEUKEMIA

EWING SARCOMA

Risk of cancer cell contamination


• One of the following sentences about ovarian grafting to preserve fertility is NOT correct

4. After transplantation, published data show acceptable pregnancy rates

1. All women freezing ovarian tissue before cancer treatment will need transplantation after being cured

2. Ovarian strip grafting can last >40 months in some cases

3. Ovarian function is recovered approximately 4 months after grafting





Garcia-Velasco et al. Fertil Steril 2013; 99: 1994-99

Oocyte vitrification for FP

40

20

0ºC

-20

-40

0.5 1.0

Time (minutes)

Vitrification

Oocyte vitrification cycles analyzed: 1807(Updated to May 2015): ‐ 1297 non oncological FP

‐ 510 oncological FP

Year Onco. FP Social FP Total FP

2007 1.8% 4.9% 6.7%

2008 1.2% 2.3% 3.5%

2009 1.2% 2.6% 3.9%

2010 2.4% 3.2% 5.6%

2011 2.4% 7.2% 9.6%

2012 2.5% 8.0% 10.5%

2013 3.0% 12.5% 15.6%

2014 2.9% 17.9% 20.8%

2015 2.8% 21.5% 24.3%

% FP procedures (MII vitrification) with respect of total oocytes vitrification procedures

Trends of FP procedures at IVI group

Nº Total Vit proc. = 21973NºTotal Social FP= 1879NºTotal Onco FP= 510

TYPE OF MALIGNANCY

Oocyte Vitrification for FPOocyte Vitrification for FP

- GnRH Antagonists, follicles ≥14 mm.- GnRH agonist when 19-21 mm

COH: Protocol with Letrozol

Letrozole

FSH 150 UI

5 10Letrozole 5 mg/d

1 4 8 122

GnRH antagonists


COH: Protocol with Letrozol

Cakmak et al. Fertil Steril 2013; 100: 1673


Garcia-Velasco et al. Fertil Steril 2013; 99: 1994-99

COH: Outcomes

Domingo et al. Fertil Steril. 2012;97:930‐4.


Titus et al. Sci Transl Med 5; 172ra21 (2013)

Diminished ovarian reserve in BRCA1-deficient individuals

Type Ca Mean Nº oocytes

P value

Mean retrievedBreast 11.9±9.1

0.838Other 11.8±8.9

Mean MII vitrifiedBreast 9.3±7.5

0.813Other 9.1±7.2


Retrieved and vitrified oocytes and age

† p<0.05

Mean 18.7 14.2 13.7 12.5 7.9

†

Retrieved oocytes

Mean 13.6 10.1 10.8 9.8 6.3

†

Vitrified oocytes

Ovarian Cortex Vitrification

FP Procedures 735 (46) 799

Attempts to Pregnancy 38 51

Clinical pregnancies (%) 15 (36.6%) 21 (40.0%)

Ongoing/Term Pregnancies (%) 8 (19.5%) 16 (28.9%)


Updated May, 2016

• Which sentence about oocyte vitrification is correct?

4. Success with oocyte vitrification is much higher than with ovarian cortex transplantation

1. Cancer patients do not have a diminished ovarian reserve pre-cancer treatment

2. Breast cancer patients yield less oocytes that othe malignancies

3. Thawing 5-10 oocytes provide 27% LBR

Realistic survival chance

Ovarian reserve assessment

(AMH/AFC)HRT‐OD

Time to treatment

Risk of malignant cell contamination

>15 days

COH

‐

Patient at risk of POI

(Chemo protocol/Pevic Radiation/Age)

AMH>5pM

AFC>6

AMH<5pM

AFC<6

<15 days

Low

High High

Risk of malignant cell contamination

F‐IVM

Low

High


• Medical protection of the gonads is promising.

• Orthotopic ovarian grafting

• Safe in most types of malignancies

• Ovarian function restored in >90% after 4 months

• Pregnancy rates around 30% (natural+IVF)

• Oocyte/embryo vitrification

• If time (and oncologyst) allows COH

• Success rates expected to be similar to ART

• 7 oocytes stored provide around 27% chance of LBR

Fertility preservation in Ca patientsTAKE-HOME MESSAGES

Fertility preservation in Ca patientsTAKE-HOME MESSAGES

Ana CoboCésar Díaz

Daniela GallianoJavier DomingoSonia HerraizJosé M. Rubio

Edurne Novella-MaestreMara Andrés

Nicolás GarridoJuan Garcia-Velasco

Carlos Simón

ACKNOWLEDGEMENT

fertility preservation for the woman with cancer€¦ · breast cancer hl nhl leukemia ewing...

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