Study That Establishes the Potential of Fertility Preservation in Young Female Patients by Oocyte in Vitro Maturation and Cryopreservation and Ovarian Cortex Cryopreservation and Transplantation
Advances in early detection and increasing success of chemotherapy have made cancer therapy
a curable disease. In children and adolescents with cancer, cure rates approach 75%. These
cure rates are achieved in great part due to the use of intensive chemotherapy, and in some
cases, radiation. The use of these treatment modalities is associated with significant
toxicity, including the potential for gonadal damage and subsequent reduced fertility.
Aggressive chemotherapy is, however, usually gonadotoxic and results in infertility in many
pediatric patients. Ovarian damage is drug and dose dependant and increases with patient age
at treatment. Increasing numbers of young cancer survivors are therefore experiencing
infertility related to their past cancer treatment. Having children thus becomes an
important issue for young cancer patients.
Cryopreservation of sperm is an effective method that is offered to pre- and post-adolescent
males. Female gametes were however, not readily amenable to cryopreservation though the use
of vitrification recently resulted in improved results. Nevertheless, this method is not
applicable for young girls as it requires prolonged induction of ovulation and vaginal
sonography to complete aspiration of oocytes. Similarly, In vitro fertilization (IVF) may be
offered only to patients beyond adolescence. Ovulation induction requires a few weeks delay
in the initiation of cancer treatment.
Since ovarian stimulation is generally not a feasible option for young girls and
adolescents, strategies for preserving fertility in these patients usually include ovarian
cryopreservation, an experimental technology with some success in animal studies, recently
resulting in few deliveries following human transplantations. Although the technique remains
investigational, it is being increasingly offered to women undergoing cancer treatment. In
prepubertal girls ovarian cryopreservation is the only option for potentially preserving
ovarian function. As we and others have shown, it is probable that methods of ovarian
transplantation with vascular anastomosis will be applied in the future.
We have recently recommended that following individual consultation by a multi-disciplinary
team, all female pediatric cancer patients and their families should be counseled regarding
side effects of chemotherapy and be offered ovarian preservation.
The methodology of ovarian cortex preservation, pioneered by Gosden is currently routine in
many centers in a few countries. Nevertheless, it is realized that the future use of this
cryopreserved ovarian cortex may be limited due to cellular injury during cryopreservation
and due to the tissue ischemic damage following transplantation.
Furthermore, cryobanking of ovarian cortex preserves only the smallest (primordial and
primary) follicles, since all preovulatory antral follicles, which contain GV stage oocytes
will not survive the procedure. We thus currently propose to all patients undergoing
ovarian cryopreservation to perform integrated oocyte aspiration from antral follicles of
the tissue, followed by in vitro maturation (IVM) and oocyte cryopreservation as an
additional fertility-preserving method. The aim of this study was to analyze oocyte
detection and IVM success rates in young girls and adolescents using this combined method.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
risks involved in laparoscopic oophorectomy
Ariel Revel, MD
Hadassah university hospital
Israel: Ministry of Health