How to preserve fertility before chemotherapy

Advances in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. Unfortunately, aggressive chemo- and radiotherapy can result in the loss of both endocrine and reproductive functions, leading to premature menopause and infertility. It is thus our duty to evaluate the effects of specific cancer treatments on fertility and discuss fertility preservation options with these young women prior to cancer treatment. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. There is conflicting evidence on the use of GnRH analogs to preserve fertility in women undergoing chemotherapy, and GnRH analogs are not indicated for patients undergoing radiotherapy. The only established method of fertility preservation is embryo cryopreservation, but this requires the patient to be of pubertal age, have a partner, and be able to undergo a cycle of ovarian stimulation. Cryopreservation of ovarian tissue is the only option available for prepubertal girls, and for woman who cannot delay the start of chemotherapy. Twenty-five cases of orthotopic reimplantation of cryopreserved ovarian tissue have so far been reported and six live births have been achieved, yielding a pregnancy rate of almost 25%. With all the advances in ovarian tissue cryobanking and reproductive technology, fertility preservation is now a real possibility for patients whose gonadal function is threatened by radioor chemotherapy. For this reason, it should be a medicolegal obligation for gynecologists, oncologists and pediatricians to systematically propose cryopreservation before initiating cancer therapy that could impair future fertility

Effect of cryopreservation and transplantation on the expression of kit ligand and anti-Mullerian hormone in human ovarian tissue.

BACKGROUNDAlthough cryopreservation and transplantation of ovarian tissue represent a promising alternative to safeguard fertility in cancer patients, low recovery rates of oocytes aspirated from antral follicles and a significant number of empty follicles have been observed in women with transplanted frozen-thawed ovarian tissue. In order to understand how freezing and/or grafting may affect follicular development, the follicular expression of kit ligand (KL) and anti-Müllerian hormone (AMH), two key factors activating and inhibiting follicle growth, were assessed after long-term grafting in severe combined immunodeficient (SCID) mice.METHODSOvarian biopsies from eight patients were used for fresh and frozen-thawed tissue xenografting in 13 SCID mice for a period of 28 weeks, including 2 weeks of gonadotrophin stimulation. KL, AMH and proliferating cell nuclear antigen (PCNA) immunostaining were quantified before and after grafting in the two treatment groups (fresh and frozen-thawed grafted ovarian tissue).RESULTSLower expression of KL was found in primordial and primary follicles after grafting of both fresh and frozen-thawed tissue. Consistent expression of AMH was found in most growing follicles at a similar rate in both graft types. In fresh and frozen-thawed grafts, 13-14% of primordial follicles were PCNA-positive, indicating a similar maintenance of quiescent follicles despite follicle activation.CONCLUSIONSGrafting and/or gonadotrophin stimulation appear to affect the follicular expression of KL, which may alter oocyte quality. AMH expression in growing follicles after ovarian tissue transplantation may be one of the factors contributing to the preservation of resting follicles in 28-week-old grafts

A review of 15 years of ovarian tissue bank activities.

PURPOSE: To review 15 years of activities in ovarian tissue cryobanking from medical database files, including patient indications, histological evaluation and clinical characteristics. METHODS: Retrospective longitudinal analysis of data from an ovarian tissue bank in an academic hospital. Five hundred and eighty-two patients had their ovarian tissue cryobanked between April 1997 and January 2012. Analysis of cryobanking database: precryopreservation patient characteristics, indications and safety issues, laboratory files and postcryopreservation clinical data. RESULTS: Of the 582 patients who had their ovarian tissue cryopreserved, 106 patients donated for research purposes and 476 patients for fertility preservation and long-term cryopreservation. Clinical data analysis of the 476 patients revealed a mean age at the time of cryopreservation of 23 ± 8.5 years (range: 9 months - 39 years), with 96.2 % of subjects aged ≤35 years (n = 458). Among 391 cases of malignant disease, hematological malignancies (39.9 %, n = 156) and breast cancer (21.7 %, n = 85) were the two main indications. At histology, malignant cells were found in ovarian tissue from leukemia patients (n = 3) and non-Hodgkin's lymphoma patients (n = 2). Eleven patients underwent autotransplantation, resulting in 5 live births and 1 ongoing pregnancy. CONCLUSION: This is the largest and most comprehensive study to describe and analyze indications and clinical patient characteristics before and after ovarian tissue cryopreservation. The procedure is safe, easy and promising. The database concept is a useful tool in patient selection for autotransplantation

Aggressive recurrent respiratory papillomatosis: A series of five consecutive patients successfully treated with adjuvant intravenous bevacizumab. A single Belgian academic center experience.

Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP

Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study.

This pilot study is the first to evaluate the risk of contamination of cryopreserved ovarian tissue from advanced-stage breast cancer patients by xenotransplantation for 6 months to immunodeficient mice, associated with more conventional screening methods. Our xenografting results are reassuring, but caution needs to be exercised, as MGB2 gene expression was detected in some cases. Larger numbers of ovarian tissue samples from patients with advanced-stage breast cancer are required to confirm our findings before ovarian tissue transplantation can be contemplated in these patients