Fertility protection: Good Cryo-Upbringing

5. August 2015
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In recent times efforts to achieve the first live birth following re-transplantation of cryopreserved, prepubertal ovarian tissue met with success. This is good news for women who have been left infertile as a result of cancer treatment. Nevertheless the fulfilment of such a wish to have a child is an expensive delight.

In an article in the June issue of the journal Humane Reproduction Belgian researchers led by Dr. Isabelle Demeestere bring attention to the fate of a young woman who at the age of thirteen had undergone a bone marrow transplantation as a result of a serious case of sickle cell anaemia. The loss of ovarian function was the consequence of the ablative chemotherapy required for the transplantation, as was expected. For this reason, at the age of 15 the patient began hormone replacement therapy. Ten years later, this woman expressed a desire to have her own child. Without having one’s own oocytes this is however not possible.

Fortunately, the doctors had thought of that possibility leading up to chemotherapy; before the treatment they removed the right ovary. Having been divided into 62 fragments, the tissue was frozen as a precautionary measure – this occurred, although the girl at this point had not yet experienced menstruation; it was therefore unclear whether the tissue removed for retransplantation would develop normally. After the woman had ceased her HRT, a part of the cryopreserved tissue was reimplanted during a laparoscopic procedure. Five months later, she began to menstruate and at the age of 27 years she was able to bring a healthy baby boy into the world.

Hope for cancer patients

In actuality, live births after transplantation of ovarian tissue had already taken place, in these instances though the donors at the time of cryopreservation were already adults. What is new is that such treatment is also possible using tissue from a premenstrual girl. “This is a major breakthrough in this area, since the patients who in the future will be most likely to use this procedure will be children”, declares Dr. Demeestere. “If diseases are diagnosed with these patients, thereby requiring therapy which will cause the destruction of the ovarian function, cryopreservation of ovarian tissue would be the only way to preserve their fertility”.

The ability to begin fertility-preserving measures so early is extremely important, especially for girls and women suffering from cancer. Although true that the survival rates for all cancers are much higher today than in earlier times, chemotherapy, radiotherapy and hormone therapy can nonetheless have a devastating effect on fertility. Once the oncological treatment has ended, the fulfilment of the wish for a child is for many patients obviously a key criterion in their quality of life. One survey published in 2014 informs us that 59% of the breast cancer-patient respondents stated that they wanted to have children in the future. Almost one in ten women even declared that they did not want to undergo chemotherapy if their fertility would as a result be restricted.

What else is possible

Whereas sperm cryopreservation is an established, cost-effective and comprehensive procedure available to men, fertility-preserving measures for women are significantly less accessible. The removal and cryopreservation of ovarian tissue is even considered an experimental method; it does however, provides some decisive advantages. The removal can be done in quick time, so that the beginning of any oncological treatment is not significantly delayed. In addition, not only can fertility be regained through this technique, so too can the gonad function. However, this effect seems to be only transient, and long-term reports are not yet available. In addition, at the heart of the matter here is a cost-intensive procedure involving techniques in which two operations (removal of ovarian tissue and retransplantation) are required. Furthermore, it needs to be ensured that the tissue does not contain any malignant cells; this appears especially with regard to haematological diseases to be a problem.

Another experimental method involves treatment using GnRH agonists (GnRHa), which after an initial gonadotropin-excretion (flare-up) leads to a downward regulation of pituitary GnRH receptors. As a result, hypogonadism occurs – the quiescent ovaries are less vulnerable to gonadotoxic agents. The advantage of this method is that it may also be carried out shortly (ie one week at the latest) prior to oncological treatment. In addition, no invasive procedure is required and the compounds required are easily accessible. The effectiveness of GnRHa treatment is however not fully understood. In addition, there exists the concern that with women who have hormone receptor-positive disease, this treatment using GnRH agonists could reduce the effectiveness of chemotherapy.

Placed in cool storage

The freezing of unfertilised or fertilised eggs is part of the standard repertoire of methods used in preserving fertility. Nevertheless, both techniques require a postponement of oncological therapy of two weeks or more, since a controlled ovarian stimulation needs to be performed, followed by transvaginal oocyte extraction. The egg cells obtained are then, following the usual process, fertilised via intracytoplasmic sperm injection and frozen in the pronucleus stage. However, when a partner’s sperm is not available, a heterologous in-vitro fertilisation using foreign sperm is the only possibility to carry out the cryopreservation process. Because this option is for many women not an unacceptable one, freezing unfertilised eggs has been established as a therapy option.

In the case that a course of oncological treatment demands irradiation of the pelvis, there exists the possibility of ovarian transposition. The usual approach involves laparoscopic transposition of one or both ovaries through the pelvic inlet towards the diaphragm, whereby the ovaries are fixed and marked with a titanium clip. After irradiation treatment, the ovaries can again be returned to their place in the pelvis. In addition, where a tumour of the female reproductive system occurs, organ-preserving surgical techniques can be a reasonable step – but only after a careful benefit/risk assessment and thorough education of the patient.

Saved for the future

In advising young patients it is especially important to actively bring the fertility issue into communication at the individual level and to inform about how great the risk is that oncological treatment actually decreases fertility. The chances of success and risks involved in fertility-preserving measures should be openly stated here. As part of the decision making process, for many patients not only should the question of future family planning play a role, but so too should the costs. Cryopreservation of unfertilised or fertilised oocytes can easily cost 4,000 Euros, and are procedures which are not normally covered by health insurance. The fact that the desire to have children is reduced to being a matter of personal luxury certainly does not help to reduce the psychological burden for cancer patients.

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Gynaecology, Medicine, Oncology

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