the STIM-trial

Raionale:Chemotherapy for breast cancer may have a negative impact

on reproductive function due to gonadotoxic damage.

Fertility preservation via banking of oocytes or embryos after

controlled ovarian stimulation with FSH (COS) may increase

the likelihood of a future successful pregnancy. It has been

hypothesized that elevated serum estrogen levels during

COS may induce growth of breast tumours. This has led to

the use of alternative COS protocols with addition of

tamoxifen or letrozole. The effectiveness of these COS

protocols in terms of oocyte yield is unknown.


Objective:To evaluate the effectiveness of COS with tamoxifen or

letrozole in terms of oocyte yield compared to standard COS

for oocyte- or embryo banking.


Study design:Randomized open-label trial

comparing COS plus tamoxifen and COS plus letrozole with

standard COS in the course of fertility preservation.


Study population:Women with

breast cancer who opt for banking of oocytes or embryos,

aged 18 – 43 years at randomisation.


Intervention : Women will receive tamoxifen 60 mg per day

orally in combination with COS or letrozole 5 mg per day

orally in combination with COS, or standard COS.


Main study parameters/endpoints: Primary outcome: the

number of oocytes retrieved at follicle aspiration. Secondary

outcomes are number of mature oocytes retrieved, number

of oocytes or embryos banked and peak E2 levels during

COS.


Nature and extent of the burden and risks associated with

participation, benefit and group relatedness:All women will undergo one

additional blood sample on the day of ovulation trigger for E2

measurement. If measurement of anti-mullerian hormone

(AMH) is not part of standard care, one extra blood sample

will be drawn for AMH measurement. In the women who

receive tamoxifen in addition to COS, in some centres

(Academic Medical Center Amsterdam and University hospital

Brussels a series of four to six measurements of tamoxifen

metabolites will be analysed in blood samples acquired

during routine blood sampling for COS.

Multiple changes are made at 21-may-2015

A low peak E2 during COS is considered to be safer than a high peak E2 in women with breast cancer

1. during COS at day of ovulation trigger with GnRHa
2. day of OPU (number of cryopreserved embryo's or oocytes)

Group 1 will receive tamoxifen (60 mg per day, orally) in addition to COS. Group 2 will receive letrozoel (5 mg per day, orally) in addition to COS. Group 3 will undergo standard COS with no additional treatment.