Brochure - Clinique OVO

2 •
• Oncology and Fertility Preservation
GYNECOLOGISTS
Dr Coralie Beauchamp
Dr Joanne Benoît
Dr François Bissonnette
Dr Bernard Couturier
Dr Robert Hemmings
Dr Jacques Kadoch
Dr Louise Lapensée
UROLOGISTS
Dr François Benard
Dr Peter Chan
Dr Armand Zini
GENETICIST
Dr Régen Drouin
GRAPHIC DESIGN: KATIA RUELLE MALKA
- COMMUNICATIONS ASSISTANT
SUMMARY
3
Incidence of Cancer
5
Gonad toxic effects of the
treatments
6
Fertility Preservation
8
Ovarian stimulation after
Cancer
12 OVO FOUNDATION
Oncology and Fertility Preservation •
INCIDENCE OF CANCER
It is estimated that approximatively 8% of malignant
neoplasms will occur before the age of 40 years old in
women.
• The progress made in the diagnosis and treatment of
neoplasms has greatly increased the patient’s life
span. It is estimated that in 2010, one adult out of 250
will be a survivor of a previously treated malignant
neoplasm.
• The surgeries and adjuvant therapies of chemotherapy
or radiotherapy can cause permanent damage to the
gonads resulting in infertility.
• In women, reproductive toxicity caused by the
surgeries and adjuvant therapies is primarily related
with the age of the patients, the type and intensity of
the treatments. Adolescents who under went a bone
marrow transplant in association with chemotherapy or
radiotherapy will generally become amenorrheic
(sterile). While, in comparison 20% of patients
30 years old or younger who have received adjuvant
chemotherapy for a breast neoplasm, will suffer from
the same effect.
• The incidence of cancers more frequently diagnosed
during the reproductive period are illustrated in
Figures 1 and 2.
• For comparisons reasons, the toxic effects of the
chemotherapy and radiotherapy agents are illustrated
in Tables 3 and 4 (following page).
• 3
4 •
• Oncology and Fertility Preservation
WOMEN 25 TO 44 YEARS OLD
NUMBER OF CASES
MEN 25 TO 45 YEARS OLD
NUMBER OF CASES
SURVEILLANCE DU CANCER, 2004 • A.S.P.C./P.H.A.C.
• 5
Oncology and Fertility Preservation •
GONADOTOXIC EFFECTS
OF THE TREATMENTS
TABLE 3
CHEMOTHERAPY/RADIOTHERAPY
RISK OF AMENORRHEA
Low risk (<20%)
Moderate risk
Elevated risk (>80%)
Methotrexate
Alkylating agents
5-Fluorouracil
Cyclophosphamide
Actinomycine D
Busulphan
Cisplatine
Bleomycine
Melphalan
Adriamycine
Vincristine
Nitrogen mustard
6-mercuptopurine
Pelvic irradiation with
Pelvic irradiation with
ovariopexy
ovariopexy
LEE + COLL / J.CLIN.ONCOL. 2006 • SONMEZER, OKTAY / HUM. REPROD. UPDATE, 2004
CANCER TREATMENT
TABLE 4
OVARIAN FUNCTION AND FERTILITY POTENTIAL
Ovarian
reserve
Chances of
spontaneous pregnancy
(%)
Amenorrhea
(%)
Premature ovarian
insufficiency (%)
Age < 20
20-50
17
28
Age > 25
80-90
60
5
Bone marrow
transplant age < 20
> 90
80-100
0
treatment
Polychemotherapy with
or with out irradiation
Radiotherapy
> 800 CGY
100
>300 CGY
60
0
< 300 CGY (ovarian
transposition)
10
10-90%
LOBO/ NEJM, 2005 ,
FALCONE + COLL. / FERTIL/STERIL, 2004
6 •
• Oncology and Fertility Preservation
FERTILITY PRESERVATION
AVALIABLE STRATEGIES
In certain cases, the use of conventional surgery will limit germinal cell
damage or damage to the uterine mucous membrane and will improve
the chances for a future conception. For example:
- Radical vaginal trachelectomy for cervical cancer 1A2-1B;
- Unilateral ovariectomy for ovarian cancer 1A1;
- Ovarian transposition before radiotherapy for Hodgkin’s
lymphoma and non-Hodgkin lymphoma.
FIGURE 5
The available strategies to preserve one’s fertility are described in table
5. One can observe a significant reduction in fertility with cancers
occurring during their reproductive period and needing adjuvant
chemotherapy treatment. A convincing example of this situation is
recognized in breast cancer, which represents 30% of all cancers
occurring in women during their reproductive period. The standard
protocols using adjuvant chemotherapy are highly toxic on the ovarian
function. (Table 6)
Proven (recognized)
Experimental
• Embryo cryopreservation
• Ovocyte cryopreservation
• Conservative gynecological surgery
• Cryopreservation of ovarian tissues or
• Ovariopexy
• Sperm cryopreservation
J.CLIN.ONCOL., 2006
testicules
• Pre-chemotherapy ovarian suppression
• 7
FIGURE 6
Oncology and Fertility Preservation •
Regime
Amenorrhea (%)
1- Cyclophosphamide + Metothrexate +
5- Fluorouracil (6 cycles) (CMF)
Ovarian reserve
A.N.(%)
68
2- Adryamicine
Cyclophosphamide +/- Taxanes (AC)
35
78
MATTLE + COLL. / EUR. J. HAEMATOL, 2005 • REH + COLL. / ASRM, 2006
FIGURE 1
In these cases, chemotherapy treatments must begin within the initial
3 months in order for it to be beneficial. Luckily, there is generally a
delay of 4-6 weeks between the surgery and the beginning of
chemotherapy therefore this period provides a sufficient time frame to
conduct an ovarian stimulation with an egg collection followed by egg
vitrification in instances where there is no partner or an in vitro
fertilization associated with an embryo cryopreservation if the patient
has a partner (Fig. 1)
Chemotherapy
Delay > 6 weeks
Emergency
or pre-puberty chemotherapy
Freezing
of embryos ovocytes
Freezing
of the ovarian cortex
Hormonosensible
treatments for breast
cancer
Stimulation
with an aromaste
inhibiteur tamoxifen +
gonadotrophines
OKTAY / CUR. OP. ONCO., 2007
Nonhormonosensible cancer
(other than breast)
Stimulation with
Antagonist Protocol
8 •
• Oncology and Fertility Preservation
In these situations, the more efficient technique in assisted
reproduction is presently a frozen embryo transfer post
chemotherapy treatments. The pregnancy rate is 30% per transfer
and the cumulative rate of pregnancy is 60%.
FIGURE 7
The freezing of eggs by conventional methods (slow freeze) is not
very effective. As a result, vitrification has become a more effective
technique. (Table 8) Certain studies were able to obtain equivalent
results for the cryopreservation/embryo transfer. This technique
offers single women, who do not want to use a donor, a reasonable
chance to conserve their reproduction. (Fig. 8)
Slow freeze
Vitrification
Before June 2005
Vitrification
After June 2005
Average age
33.7
32.3
32.3
Fertilisation rate (%)
64.9
70.6
75.4
Implantation rate (%)
10
8.8
20.5
Live births (%)
thawed eggs
1.7
2
4.6
Live births (%)
transfers
15.6
29.4
39
OKTAY / FERTIL/ STERIL, 2006
OVARIAN STIMULATION AFTER CANCER
IN VITRO FERTILIZATION
PRE-POST CHEMOTHERAPY NATURAL/STIMULATED CYCLE
In order to obtain reasonable chances of conception, embryo and egg
cryopreservation are available and efficient techniques. However, they must be
offered prior to the chemotherapy and in combination with a stimulated cycle.
(Fig. 9).
• 9
FIGURE 9
Oncology and Fertility Preservation •
Stimulated IVF
Natural IVF
(1)
Pre-chemo (2)
Pre-chemo (3)
Average age
34
35.7
36.5
No cycles
84
76
38
94
89
73
13
62.5
13.2
Cycle with collection (%)
Pregnancy/cycle
1. KADOCH J + ASS./REPROD. BIOMED ONLINE, 2008 • 2. AZIM + OKTAY / JCEM, 2006
• An ovarian stimulation pre-chemotherapy or pregnancy post chemotherapy,
will not affect the patient’s chance of survival.
In fact, the survival rate is better if there is a subsequent pregnancy.
(CONNEL + COLL. HEALT CARE WOMEN INT., 2006)
• There is no evidence of an increase in malformations in newborns born to
patients having received chemotherapy, if the conception took place one or
more years after the treatment.
IVF
3/42
RECURRENCE
2 tamoxifen
BREAST CANCER AND IVF
1 tamoxifen/FSH
0 letrozole
Controlled
OKTAY + COLL. A.S.R.M., 2007
4/44
10 •
• Oncology and Fertility Preservation
SAFE PREGNANCIES
AFTER BREAST CANCER
GELBER ET AL, 2001
STIMULATION PROTOCOL
OVARIAN /IVF PRE-CHEMOTHERAPY
FIGURE 12
The ovarian stimulation protocol associating letrozole (FMR) to the
gonadotropine(FSH), offers the safest option while maintaining the best success
rates. (Fig. 12, 13 & 14).
TMX
TMX + FSH
FMR + FSH
FSH
36.6
38.3
36.2
36.9
FSH D 3
9.4
9.4
7.2
4.3
E2 max
419
1182
405
1453
Foll > 17mm
1.2
2.6
3.6
2.6
Mature ovocytes
1.5
5.1
8
9.2
Embryos 2PN
1.3
3.8
5.3
6.6
Age
OKTAY + ASS., JCEM, 2006
• 11
Oncology and Fertility Preservation •
STIMULATION PROTOCOL FOR PATIENTS
DIAGNOSED WITH BREAST CANCER
TAMOXIFEN AND LETROZOLE
HCG
JOURS ADMINISTRATION
TAMOXIFEN 60MG/J
Tam. FIV
E2
7.8 ± 0.5
E2
8.9 ±0.8
FSH 150IU
TAMOXIFEN 60MG/J
Tam. FSH-FIV
FSH 150IU
LETROZOLE
LETROZOLE 5MG/J
Letrozole FIV
0
4
8
9.1 ± 0.5
E2
12
DAYS OF CYCLE
OKTAY ET AL. J. CLIN. ONCOL., 2005;23(19):4347-53
LETROZOLE-FSH PROTOCOL
ANTAGONIST
ANTAGONIST
HCG
RETRIVEAL
FSH
LETROZOLE
E2
DAY 21
LETROZOLE
3
5
7
9
E2
12 •
• Oncology and Fertility Preservation
OVO FOUNDATION
The OVO CLINIC proudly
announces the launching of the
OVO FOUNDATION.
The main goal of
this foundation is to provide a
financial support to patients
diagnosed with a neoplasm and
who wish to preserve their
fertility.
It is now possible to benefit
from the cyropreservation of
the gametes (sperm or ovocytes)
or embryos prior to undergoing a
gonad toxic treatment.

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