Cancer treatment is about to start

If you – or your child – have to undergo cancer treatment and you are concerned about the consequences for your fertility or that of your child, then you should first talk to your oncologist. He knows the potential harmful effects of the treatment that has been prescribed to you and may be able to give you a prognosis about its impact on your fertility.
At the same time you should also contact the Oncofertility team at UZ Brussel. We can give you all the information about the options to safeguard your fertility or that of your child.
Cancer treatment should usually be started as soon as possible. Therefore, limited time is available for fertility preservation – sometimes up to two weeks, but sometimes only a few days.
Therefore, we have to act quickly: contact.

As mentioned in ‘Cancer and your fertility’ the (in)fertility of girls and women is closely related to the number of egg cells that is (still) available. These are contained in small vesicles (follicles) which are stored in both ovaries. Almost every cancer therapy – both chemo and radiotherapy – have a negative impact on the stock of follicles. A number of approaches are available before the start of the treatment to try and safeguard fertility.

Women who do not (yet) have a partner and are facing cancer treatment can choose to ‘bank’ unfertilized eggs. This means that these eggs are frozen and preserved.

Thanks to the development of a rapid freezing technique called vitrification, it has become possible to freeze mature egg cells with a high chance of survival after thawing. For your information: ovary tissue is currently usually frozen by means of a method of slow freezing.
   
There are three techniques to bank egg cells:
  1. let them become mature in the body, then collect and freeze them (see Stimulation and egg cell pick-up).
  2. remove them from the body in their immature phase, then mature them in the laboratory and freeze them (see in vitro maturation - IVM).
  3. freeze them while they are embedded in the ovary tissue that we removed surgically (see Ovariectomy).

Please make sure to also read the information about the legal storage time of gametes. Certainly for cryopreservation in the context of cancer treatment this information is crucial.

1. Stimulation of ovaries and egg cell pick-up  

In the appropriate circumstances you may consider to have mature egg cells, obtained after hormonal stimulation, banked before you start cancer treatment. This means:
  • the type of cancer you have allows for the treatment to be postponed a couple of weeks and up to one month, and
  • hormonal stimulation is not contra indicated.

The decision about this can obviously only be taken in consultation with your oncologist and the CRG fertility specialist.

Hormonal stimulation aims to mature several egg cells within one menstrual cycle. At an exactly timed moment the egg cells are collected transvaginally, after which they can be banked.
The treatment is the same as for a 'normal' fertility treatment. Therefore make sure to read IVF/ICSI – The treatment step by step, from hormonal stimulation to egg cell pick-up and the egg cell bank.

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2. In vitro maturation of egg cells (IVM)  

Sometimes a course of hormonal stimulation with retrieval of mature egg cells is not possible because of time restrictions.
In that case we can collect immature egg cells before the start of the cancer treatment, followed by in vitro maturation (IVM).

We perform an ovarian puncture without hormonal stimulation or with very limited hormonal stimulation (see below for the technique). This is how we can collect immature egg cells which are then left to become mature in the laboratory in a specifically designed culture medium.

IVM is a patient-friendly technique, which can be performed within a limited time frame. That is why it is increasingly being applied in the setting of fertility preservation.
Not only is it a good alternative when an egg cell pick-up following hormonal stimulation is not an option by lack of time. In cases where there is a high risk that cancer cells may have metastasised to the ovary, the storage of egg cells after IVM is also a safer technique than banking ovarian tissue.
The disadvantage is, however, that after IVM less mature egg cells are available than when the ovaries are stimulated.

  • IVM after an ovarian puncture
Whether ovarian puncture is useful and possible in your case depends, among other things, on the question whether your ovaries contain a sufficient amount of follicles, although there are no guidelines about the minimally required number.

Like previously mentioned only minimal hormonal stimulation of the ovaries (or even no stimulation at all) is required for an IVM treatment. We can usually collect the egg cells within a few days after the ultrasound evaluation.
However: IVM is not indicated in the period around the ovulation.

The procedure is performed under ultrasound monitoring and under local anaesthesia, or under general anaesthesia upon request.
The follicles will be punctured transvaginally. The egg cells thus collected will mature in the laboratory in a specific environment for 24 to 48 hours. The matured egg cells can then be frozen and preserved.
Another option is that we fertilize the egg cells with your partner's sperm. We do this through ICSI (injection of one sperm cell in each egg cell) because that technique offers the best guarantee for fertilised egg cells. The embryos thus generated are frozen and preserved.

Please make sure to also read the information about the legal storage time of gametes and embryos. Certainly for cryopreservation in the context of cancer treatment this information is crucial.

  • IVM in combination with ovariectomy and banking ovary tissue
Also if you decide, in consultation with the Oncofertility team, to have one ovary surgically removed for cryostorage of ovarian tissue, there is the option of collecting a number of immature cells in the laboratory phase for IVM.
In other words: not only ovarian tissue is frozen which contains follicles with immature cells, a number of cells are also matured as described above and then frozen or fertilized.

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3. One-sided ovariectomy – the procedure   

Ovaries are a few centimetres in size and can easily be reached with keyhole surgery (laparoscopy). Via this route we can remove one ovary with minimal risk of complications.
In order to see the ovaries with the laparoscope, the surgeon will first fill the abdomen with air. A surgical laparoscopy typically involves three small incisions (< between 5 mm and 2 cm) in the abdominal wall: one to insert the air and the laparoscope and two for the tools.

The procedure takes place under general anaesthesia and requires a (day's) admission to the hospital. In the six hours prior to the procedure you (or your daughter) are (is) no longer allowed to drink (or smoke!). The entire procedure, including stitching up the incisions, takes about forty minutes.
Usually you will be allowed to eat again after six hours. We ask you to stay in bed during the first twelve hours, because the anaesthesia has weakened you. The insufflation with air may cause discomfort in your abdomen for one or two days. The incisions of the procedure will heal after one week, and we will be able to remove the stitches after seven days.

The procedure is performed after written 'informed consent' containing an explanation about the procedure and the scientific state of affairs. In that document you give your permission for the procedure and you define what must happen with the cryopreserved material after the end of the storage period.
The costs of the procedure are covered by the Belgian public health insurance, obviously to the extent that you meet the conditions of affiliation.

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Cryopreservation of ovary tissue

We put cortex (the outside) tissue fragments of the removed ovary, containing the primordial follicles, into a tissue bank.
The tissue can be preserved without limitations at a freeze temperature of -196°C. At that temperature all biological processes are stopped and no ageing can occur.

However, a maximum preservation time is defined by law: click on the link and read the relevant information. Certainly for cryopreservation in the context of cancer treatment this information is crucial.

In What if you want to have children? Ovary transplantation we discuss how we can use the banked tissue with egg cells at a later time to try and repair your fertility.
It is promising that in the meantime more than thirty children have been born through assisted fertilization in which thawed ovarian tissue was used.
At the same time we have to emphasise that we can give no guarantee with regard to pregnancy and live birth. It can neither be guaranteed that cryostorage of your ovary tissue will result in a successful transplantation, nor that a successful transplantation will result in the re-initiation of the egg maturation process. We are still dealing with an experimental technique.

That is why ovariectomy and cryostorage of ovary tissue should only be considered when the risk of becoming sterile due to cancer treatment is very high. Parents can only take this decision for their underage daughter after meeting and in consultation with the oncologist, the radiotherapist and the gynaecologist.

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If you have a heterosexual relation and you and your partner have a desire to have a child, you may consider undergoing a fertility treatment before the start of your cancer treatment up to the development of embryos. In this respect see IVF/ICSI – Step by step, from 'hormonal stimulation' up to 'At the laboratory’.

Briefly, you undergo hormonal stimulation and have mature egg cells collected, which are then fertilized with your partner's sperm at the laboratory. The resulting embryos can be stored in the tissue bank.
After you are cured from cancer, you can proceed with the second part of the fertility treatment: the replacement of one (or two) thawed embryo(s) in your womb which was prepared with adequate hormonal treatment. Again refer to IVF/ICSI – Step by step, the replacement of thawed embryos.

Of course, this option will only be available if your cancer treatment can be postponed by two to four weeks and if the stimulation of your ovaries does not promote the further growth or metastasis of the cancer growth.

Please note! The maximum storage time for embryos is five years. For medical reasons – and on request! – this term can be extended.
When the pelvis is irradiated, a direct harmful effect on all organs in that area ensues. Because of this, it may be an option to (temporarily) displace the ovaries before the start of radiotherapy to a higher position in the abdominal cavity. This is called ovarian transposition.
The objective is to move them away from the area receiving radiation therapy and to shield them better from the radiation by means of neighbouring tissues. The procedure is also called 'ovariopexy' and is usually performed by means of keyhole surgery (laparascopy).
In the majority of cases, the ovaries continue to function normally in hormonal terms and the egg cells can be collected later for an IVF/ICSI procedure.
Unfortunately, the transposition of ovaries is not guaranteed effective: it is still possible that the follicle reserve is affected due to indirect radiation. The preservation of the ovarian function also depends on your age and the radiation extent and dose.
In order to increase your chances of having a baby after you have been cured from cancer, a tailor-made treatment is outlined for you. It will usually involve a combination of the above techniques. We will also weigh different factors such as your age, your ovarian reserve, the type of tumour and the toxicity of the cancer treatment. After multidisciplinary discussion we will come up with a proposal for treatment that does not compromise the start or the efficiency of your cancer treatment, but which provides maximal protection of your fertility.

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