In vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are fully established methods of assisted reproduction which can be used for patients awaiting cytotoxic therapy. After stimulating the ovaries, oocytes are transvaginally retrieved and fertilised. The oocytes are cryopreserved in the pronuclear stage, i.e. shortly before the fusion of the female and male pronucleus. The advantage of these treatments lies in the high pregnancy rate which can be achieved with cryopreserved, fertilised oocytes. An average of >10 oocytes can be retrieved per stimulation cycle with a fertilisation rate of around 55% (German IVF register). The average pregnancy rate per transfer of around 2 cryopreserved prenuclear cells is just under 20% (German IVF register).
If you consider that these numbers are based on women whose pregnancy chance is limited due to their average age of around 35 and due to other factors limiting their fertility, it may be that the pregnancy rate of women who have undergone a tumor disease is increased. If a sufficient number of oocytes can be retrieved and all cryopreserved fertilised oocytes are transferred, the average cumulative pregnancy rate can be up to 40%.
However, some aspects of these well-established methods of assisted reproduction need special attention when they are used as fertility protection measures.
Firstly, ovarian stimulation requires a time window of typically 2-5 weeks during which no cytotoxic therapy must be applied. However, in the framework of FertiPROTEKT, some modified stimulation regimens have been successfully tested which only a require a time window of 2 weeks (von Wolff et al., 2008, Fertil Steril, in press). Such a time window is often available if the patients present early to an experienced centre (contacts) in order to be treated for rheumatic diseases, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and breast cancer.
Furthermore, in the case of a hormone-dependent carcinoma such as breast cancer, which is receptor-positive (ER/PR) in around 50% of young women, the hormonal stimulation must be discussed at length. For example, under ovarian stimulation, it is theoretically possible that tumor cell growth is accelerated, which could theoretically increase the likelihood of a relapse. However, what militates against this assumption is that the young patient will maintain her menstrual cycle right up to the chemotherapy even without fertility protection measures, so she will have a high endogenous estrogen level. It is unlikely that the short-term increase of these estrogen levels caused by ovarian stimulation will significantly accelerate tumor growth. However, there are no scientific data to support this assumption. In addition, the relapse risk of patients getting pregnant immediately after treatment for breast cancer does not seem to be increased.
There are also methods to strongly reduce the estrogen levels under stimulation treatment. For example, the patient can be treated with aromatase inhibitors in addition to the gonadotrophins so that the estrogen levels in blood are much lower. Experience with this stimulation is limited but very promising (Oktay et al., 2006, J Clin Endocrinol Metab, 91: 3885-3890).
Alternatively, it is possible to retrieve immature oocytes with no or very mild gonadotrophin stimulation and to mature them before the cryopreservation (in vitro maturation, IVM). However, only relatively few oocytes can be obtained with this method, which is only performed in a small number of centres. Therefore, this technique should not be used as a sole measure but combined with another method such as the cryopreservation of ovarian tissue.
Finally, the patient needs to live in a stable relationship since the oocytes are fertilised prior to cryopreservation for IVF and ICSI. If the patient has no partner, the oocytes can be cryopreserved without prior fertilisation.