Sveafertil Project: Impact of Medical Treatments on the Ovary

Some life-saving medical treatments can have serious side effects. For example, treatments for cancer and therapies for bone marrow transplantations can damage the ovaries. Ovaries contain immature eggs and are an essential part of the female reproductive system. If treatment-related damage is extensive, the ovaries may be permanently affected. This may lead to difficulties becoming pregnant and could result in infertility later in life. If the patient is very young when treatment is given, puberty may also be affected, as healthy ovaries are essential for development to sexual maturity.

For adult women, fertility can be preserved by collecting and freezing (cryopreserving) mature eggs before treatment begins. If the patient is a young girl who has not gone through puberty yet, there are no mature eggs that could be cryopreserved. For the young patient, ovarian tissue containing immature eggs can be collected and cryopreserved instead. Cryopreservation of ovarian tissue is an established method for adult women to preserve fertility. For children, the method is less studied, and it is not yet part of routinely clinical care. More research is needed to understand the possibilities and limitations of fertility preservation in young girls.

Sveafertil is a fertility preservation study for girls and young women that has received ethical approval from the Swedish Ethical Review Authority. The project brings together all pediatric oncology and hematology units in Sweden, giving girls and young women at very high risk of treatment-induced infertility the possibility to preserve their fertility. 

Sveafertil was initiated in 2020 and serves two main functions:

1. Sveafertil enables patients to clinically cryopreserve a piece of their ovarian tissue for their own possible later use in fertility treatments
2. Sveafertil carries out fundamental research on child ovarian structure and function to understand the possibilities and limitations of fertility preservation in children

Fertility preservation

Ovaries together with immature eggs develop early during foetal development before birth. Therefore, a newborn girl already has a reserve of immature eggs in her ovaries. These eggs remain immature until she reaches puberty when the body’s hormonal system becomes active and stimulates maturation of eggs. For this reason, pubertal development is an important consideration when planning fertility preservation. If the patient has gone through puberty, the possibility to collect mature eggs to preserve fertility should be considered. If the patient has not gone through puberty, there are no mature eggs available, and the only option to preserve fertility is to collect and cryopreserve a piece of ovarian tissue that contains immature eggs.

Sometimes ovarian tissue is collected for fertility preservation in adult women too. For example, if cancer treatments must be started immediately, ovarian tissue collection is the only procedure that can be performed rapidly because collection of mature eggs takes several weeks. A small piece of ovarian tissue is surgically removed and stored at -180 °C. When the woman has recovered from her disease and wishes for pregnancy, the frozen ovarian tissue can be thawed and transplanted back. More than 200 babies have been born worldwide following ovarian tissue transplantation. The method is now considered established clinical routine for adult women. However, information on the suitability of this procedure for young girls, especially before puberty, is limited. To date, only three reported cases have resulted in pregnancies after transplantation of ovarian tissue that was collected during childhood. In these cases, the girls were around 9-14 years old when the ovarian tissue was removed for freezing. It is not yet known whether the method is effective for even younger patients. Importantly, tissue transplantation is not an option for all patients because the tissue may contain cancer cells that could cause the disease to return. This is the case for blood cancers like leukemias and lymphomas. For these patients, maturation of eggs in the laboratory could be an option in the future. However, no such method exists today.

Sveafertil Setup

Sveafertil is open to patients between 1 and 17 years of age who meet the study’s inclusion and exclusion criteria. Girls before puberty who are at very high risk of infertility, and adolescents after puberty who are at high risk of infertility, may be included in the study if the doctor judges that there is no increased risk for surgical complications. The risk of infertility is assessed according to recommendations from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) and Swedish national guidelines that are based on treatments, not diagnoses. Fertility consultation is provided to the family, and information about Sveafertil is provided. Families who wish to participate provide informed consent together with their daughter. A piece of ovarian tissue is surgically removed under general anaesthesia and sent immediately to Karolinska University Hospital in Stockholm. Two-thirds of the tissue piece is clinically cryopreserved and stored for the child’s potential future fertility treatment. The remaining one-third of the piece is given to research that is carried out by Prof. Damdimopoulou’s research group at Karolinska Institutet.

The main research questions in Sveafertil are:

• What types of cells are found in the ovaries of children? Are these cells similar to those in adult ovarian tissue?
• How similar are the immature eggs in child ovaries compared to those in adult ovaries?
• How is ovarian tissue affected by medical treatments?
• Can immature eggs from child ovaries be matured in the laboratory?

Contact

Kirsi Jahnukainen

Pauliina Damdimopoulou

Ilmatar Rooda

Nina Boskovic

Jasmin Hassan