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 harbor immature eggs and are an essential part of the reproductive system in women. If the damage caused by treatments is extensive, ovaries could be permanently harmed. This could lead to difficulties getting pregnant and infertility later in life. If the patient is very young at the time of treatments, puberty could 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 the damaging treatments are started. 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 a routinely provided clinical treatment yet. More research is needed to understand the possibilities and limitations of fertility preservation in girls.

Sveafertil is a fertility preservation study for girls and young women that has received an ethical approval from the Swedish Ethical Review Authority. The project brings together all pediatric oncology and hematology units in Sweden, thereby giving all girls and young women in 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 fetal development before birth. Therefore, a newborn girl has already a stock 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. Consequently, puberty is an important factor when fertility preservation is planned. If the patient has undergone 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 piece of ovarian tissue is surgically removed and stored in -180 °C. When the woman has recovered from cancer and wishes for pregnancy, the frozen ovarian tissue can be thawed and transplanted back. There are over 130 babies born after ovarian tissue transplantation in the world. The method is now considered established clinical routine for adult women. However, information on the suitability of this procedure for young girls is limited. There are only two known cases where ovarian tissue collected from girls have led to pregnancies after transplantation. In these cases, the girls were around 10 years old when the ovarian tissue was removed. We do not know if the method works for even younger patients. Importantly, tissue transplantation is not an option for all patients because the tissue may contain cancer cells that could return to the patient. 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 dedicated to patients between 1 and 17 years of age who fit the inclusion and exclusion criteria. Girls before puberty in very high risk of infertility, and adolescents after puberty in high risk of infertility, can be included to the study if the doctor judges that there is no increased risk for surgical complications. The risk for infertility is determined by international 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 sign the consent forms together with their daughter. A piece of one ovary is surgically removed under general anesthesia and sent immediately to Karolinska University Hospital in Stockholm. Two thirds of the tissue will be clinically cryopreserved for the child. This piece is reserved for her possible future fertility treatments and cannot be used in research. The remaining piece is given to research that is carried out by Dr. Damdimopoulou’s research group at Karolinska Institutet.

The main research questions in Sveafertil are:

• What kind of cells is child ovarian tissue made of? 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?
• In what way is the ovarian tissue damaged by treatments?
• Can immature eggs from child ovaries be matured in the laboratory?

Funding

Sveafertil is established and funded with financial support from Childhood Cancer Fund (Barncancerfonden) and Karolinska Institutet.