Ovarian tissue cryopreservation in prepubertal patients with oncological diseases: multidisciplinary approach and outcomes.

In children with cancer, the issues related to the quality of life are becoming increasingly important together with the improvement of survival rates. This creates an entirely new challenge - minimizing the toxicity of the antitumor therapy without reducing its effectiveness. One of the specific side effects of the antitumor therapy is gonadotoxicity, which negatively affects both the somatic and mental state of the survivors. Since ovarian stimulation is ineffective in prepubertal patients, ovarian tissue cryopreservation (OTC) remains the most promising option to preserve fertility. The primary goal of this publication is to emphasize the importance of the reproductive health problem in girls with oncological diseases, with a description of the current data of international literature on the prospects of OTC in order to preserve fertility. Another goal is to present a multidisciplinary strategy for the management of prepubertal age patients with the oncological disease within the framework of the Oncological Fertility Project at Almazov National Medical Research Center. Based on the data of Russian and international literature, as well as existing guidelines and recommendations on reproductive health, a single algorithm for selecting patients has been developed, considering the expected gonadal toxicity for the use of the OTC in prepubertal girls. The developed algorithm allows identifying patients of prepubertal age, requiring the use of new possibilities of reproductive technologies. In a long-term date, we are planning to evaluate the effectiveness of the orthotopic reimplantation technique of the cryopreserved ovarian tissue in restoring the reproductive function. A multidisciplinary team of specialists and the possibilities of the Federal Center facilitate implementing the Oncofertility Program in routine practice for girls and young women, receiving gonadotoxic treatment.

Autotransplantation of cryopreserved ovarian tissue--effective method of fertility preservation in cancer patients.

OBJECTIVE: To review the literature and to present the latest advances in the autotransplantation of cryopreserved ovarian tissue. MATERIALS AND METHODS: A literature review was conducted for all relevant articles assessing the fertility preservation, ovarian tissue transplantation, standard freezing and vitrification of ovarian tissue. RESULTS: One of the promising and effective methods for fertility preservation may be the autotransplantation of cryopreserved ovarian tissue. At present, 30 babies have been born after orthotopic autotransplantation of frozen-thawed human ovarian tissue. Restoration of ovarian activity occurs between 3.5 months and 6.5 months. The longevity of autotransplanted ovarian tissue is about 5-7 years. The follicles are similarly preserved after all freezing methods; however, the ovarian stroma is significantly better preserved after vitrification than after slow freezing. An important topic for further research is preparation of the "vascular bed", optimization of vitrification technique and the development of alternative procedures to avoid the transmission of cancer cells via ovarian tissue autotransplantation - "artificial ovary". CONCLUSIONS: Cryopreservation of ovarian tissue has unique advantages over other strategies. This method: (1) does not delay cancer treatment; (2) is safer for hormone dependent malignancy; (3) can be done independent of menstrual cycles; (4) is the only option for prepubertal girls; (5) can restore not only fertility but endocrine function.

Human leucocyte antigen (HLA) A2 as a negative clinical prognostic factor in patients with advanced ovarian cancer.

OBJECTIVES: Major histocompatibility complex antigens are mandatory for the immune response, and a genetic imbalance may be linked to tumor escape. We have previously characterized a cluster of ovarian cancer patients with high incidence of HLA-A2. To find a prognostic relevance, the presence of HLA-A2 was correlated to defined clinical parameters. METHODS: A population-based set of 97 patients with confirmed epithelial ovarian cancer were recorded in a database by age, histology, stage, surgery and treatment. At the time the study was initiated, the majority of the patients were not alive and HLA-A2 expression was therefore determined by PCR/sequence-specific oligonucleotide hybridization using DNA extracted from paraffin-imbedded tissue specimens. RESULTS: 88 patients with a median age of 65 years (36-87) could be evaluated. 44% were serous adenocarcinomas, 28% endometrioid, 6% mucinous, 13% clear cell carcinomas, 7% undifferentiated and 2% other epithelial tumors. Stages I-II comprised 33% and stages III-IV 67%. In stages III-IV and serous histology, 73% were HLA-A2 positive. Cox analysis, in this group, showed high univariate (HR7.16; CI 2.04-25.03; P = 0.002) and multivariate (HR 6.8; CI 2.10-22.4; P = 0.001) Hazard Ratios. None of the HLA-A2 positive patients survived 5 years, compared to more than 50% of the HLA-A2 negative patients. CONCLUSIONS: HLA-A2 is a negative factor for survival in women with serous adenocarcinomas of the ovary in stages III-IV. This finding has implications for clinical patient management. Association with known oncogenes needs further analysis.