Aspects of ovarian stimulation protocols prior to chemotherapy for breast cancer

Maximising the yield of oocytes in breast cancer patients during fertility preservation treatment is a key target, while, at the same time, maintaining low serum oestrogen levels to avoid a risk of tumour acceleration. 

Breast cancer has become the commonest malignancy in women of reproductive age, resulting in delayed pregnancy and infertility, commonly presenting as chemotherapy related toxicity on ovarian function. Fertility preservation treatments, such as oocyte and embryo cryopreservation, have been proposed to deal with the unwanted side-effects of breast cancer and its treatment. Achieving satisfactory results, in terms of numbers of oocytes retrieved during ovarian stimulation, depends on two critical factors, the timing of ovarian stimulation initiation, as well as strategies to maximise the final number of oocytes retrieved prior to chemotherapy.

Time schedules for chemotherapy in breast cancer patients are on urgent basis, so it is crucial that any treatment including ovarian stimulation has to start as soon as possible following diagnosis. Conventional ovarian stimulation had that treatment started with menses, however, random start stimulation protocols have been tested over the past few years with comparable results in terms of numbers of oocytes retrieved. 

The second factor highlights the need to maximise the number of oocytes retrieved, as for many women this may be their best chance of preserving genetic material. Moreover, many women diagnosed with breast cancer may already have a reduced ovarian reserve, as recent studies have suggested, the reason being either advancing age, or gene mutations that are linked to risk of breast cancer. In order to obtain a higher number of oocytes double ovarian stimulations have been administered, the idea being that continuous development of new follicles in the ovaries provides a chance to repeat the stimulation protocol over the period of a few days. Some studies have looked at ovarian stimulation being repeated with an interval of menses, while other studies have examined the possibility of a second stimulation cycle during the same menstrual cycle, also known as back to back treatment. Results of these studies suggest that double ovarian stimulation protocols provide a higher total number of oocytes compared with single stimulation only.

Finally, a lot of research has been focused on the role of letrozole, an aromatase inhibitor that, when given along with gonadotropins to stimulate the ovaries, keeps the oestrogen levels low, so that the tumour cells do not get further stimuli to accelerate. Studies are suggesting that letrozole not only does not affect the final number of oocytes retrieved, it keeps the oestrogen levels significantly lower, maintaining a near normal level of oestrogen during ovarian stimulation.

Overall, according to latest research, fertility preservation strategies in women with breast cancer are 3-fold: first, immediate initiation of ovarian stimulation prior to chemotherapy, second, maximising the number of oocytes retrieved and third, maintaining a low oestrogen environment to avoid risk of tumour acceleration.

References:

1. 1. Fertility preservation for women with breast cancer before chemotherapy: a systematic review and meta-analysis. doi.org/10.1016/j.rbmo.2021.08.003

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