Treatment options

Fertility preservation in patients prior to receiving cancer treatment

The survival rates of young patients suffering from cancer have improved dramatically in recent years due to advances in diagnostic techniques and treatments. With the cure rate for many childhood malignancies now between 70% and 90%, infertility becomes an increasingly important issue. It is estimated that by the year 2010, 1 in every 250 adults will be a childhood cancer survivor.

Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise children. Both chemotherapy and radiotherapy often cause infertility due to damage to the ovaries in women and to the testicles in men, a combination of chemotherapy and radiotherapy will produce additive damage to ovaries and testicles. The damage could be temporary or permanent, it is impossible to predict who will suffer permanent damage.

Advances in the field of assisted reproductive technology (ART) provide hope that the reproductive impact of cancer therapy can be reduced.

What are the options for female patients prior to receiving cancer treatment?

• Ovarian tissue freezing
• Mature egg freezing
• IVF and embryo freezing
• Ovarian transposition
• Treatment of cancer, and see what happens
  • Retain ovarian function - natural conception with fertility treatment as required
  • Loss of ovarian function - IVF with donated eggs
• Surrogacy if the cancer patient's uterus has been surgically removed or the endometrium destroyed by radiotherapy
• Adoption

Ovarian tissue freezing

Ovarian tissue freezing is offered to young girls and single women. Ovarian tissue can be collected by laparoscopy without delaying chemo/radiotherapy and frozen as small fragments. Tissue can be used either for isolation of follicles or in-vitro culture. After culture, follicles can be isolated, eggs collected for further in-vitro maturation, fertilization with husband/partner sperm and embryo transfer. Alternatively, ovarian tissue can be auto-transplanted either in original location to allow for natural conception or at a different site (such as an arm) to allow for IVF, egg collection and embryo transfer. Ovarian tissue freezing is still very much a research tool and most work has been done in animal models. Promising results in humans but it has disadvantages such as the inability to assess quantity and quality of the follicle population, the potential risk of malignancy transmission, follicle death during procedure and irregular distribution of follicle population in human ovaries which may be a risk when ovarian tissue is cut into 1-2 mm3 fragments. There have been only two live births in humans to date. Ovarian tissue freezing is not an option for women with ovarian cancer.

Cryopreservation of isolated immature follicles can avoid transmission of malignant cells as the zona pellucida is impermeable. Unfortunately this technique is also still in research stages with no human pregnancies. Problems include th need for the patient to be fit for the procedue and the high cost.

IVF and mature egg freezing

This is an option for women without a partner or those who do not wish to use donor sperm for IVF. Patient needs to undergo controlled ovarian stimulation and transvaginal egg collection. Other problems include the time taken (2-3 weeks for ovarian stimulation), cost, and risks associated with egg collection. In addition, egg freezing itself is a risk in Oestrogen-receptor positive cancers or epithelial ovarian cancers.

There are two methods for freezing eggs:

• The traditional “slow freeze” method where the eggs are frozen slowly using cryoprotectants, placed in a vial or straw and cooled gradually. At -32° C the straw is put into liquid nitrogen (-196° C). This technique results in one baby per 100 eggs.
• Vitrification “ultrarapid freezing”. This is a new method where the vial or straw is plunged directly into liquid nitrogen, the cooling rates are so rapid that ice crystals does not have a chance to form, and the mixture of cryoprotectant and egg forms a “glass-like” solidification of cells. Vitrifaction method appears to be associated with a significantly higher survival rates compared to slow freezing. Results appear promising – approximately 10 babies are born per 100 eggs and it is much simpler technique (Petracco et al ESHRE 2007).

IVF and embryo freezing

This is probably the best option at present given long experience with technique. Can be offered to those in stable heterosexual relationship using controlled ovarian stimulation followed by IVF or ICSI. In single women, IVF with donor sperm is an option. Problems include: time taken (about 2-4 weeks) and cost. In addition, IVF and embryo freezing is a risk in Oestrogen-receptor positive cancers or epithelial ovarian cancer.

Ovarian transposition

Ovarian transposition is where ovaries are replaced away from the radiation field ans is an option prior to radiotherapy. If IVF is needed in the future, tranvaginal egg collection will not be possible if ovaries high up. Laparoscopic collection may be possible though potentially hazardous in the presence of major abdominal scarring (following surgery). Transposition can be performed laparoscopicaly just before the start of radiotherapy.

Current practice

The only technique, which can be arranged and carried out quickly, is ovarian cryopreservation. The procedure does, however, involve a general anaesthetic and an operative laparoscopy. Appropriately skilled medical and laboratory staffs need to be available together with theatre time and equipment. The procedure is only at early research stage in humans with little data on success rates or potential abnormalities in any children, which may result at some time in the future (may be in 5-10 years) when the necessary technology is developed.

Egg freezing has a very poor success rate of about 1 per 100 eggs. Embryo freezing following IVF / ICSI has a better rate of more than 1 per 7 embryos. Both require ovarian stimulation followed by a transvaginal ultrasound egg collection under intra-venous sedation. The process takes about four weeks. The major drawback therefore is an unacceptable delay in starting treatment for the majority of malignancies.

What are the options for male patients prior to receiving cancer treatment?

• Freezing semen: Freezing of the ejaculated sperm is a well established technique. This option should be offered to all post-puberty boys and adults. If the patient is unable to ejaculate, sperm may be recovered by PESA or TESA. About 50% of men with cancer will have reduced sperm quality prior to starting their chemotherapy or radiotherapy. However recent advances in Assisted Reproductive Technology have enabled many men with only a few sperm to father their children.

• Freezing testicular biopsy and later transplantation of spermatogonial stem cells: This is currently successful in animals, and application in humans seems likely in the near future, and if so this would be a milestone in preserving fertility in childhood cancer.
  
• Use of donor sperm

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