scholarly journals Safety of Ovarian Tissue Autotransplantation for Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Laurence Bockstaele ◽  
Sophie Tsepelidis ◽  
Julie Dechene ◽  
Yvon Englert ◽  
Isabelle Demeestere
Keyword(s):  
Cancer Cells ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Young Women ◽  
Premature Ovarian Failure ◽  
Ovarian Tissue ◽  
Malignant Cells ◽  
Cancer Treatments ◽  
Ovarian Cortex ◽  
Human Ovarian Tissue

Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance.

scholarly journals The role of gonadotropin-releasing hormone agonists in female fertility preservation

2021 ◽  
Vol 48 (1) ◽  
pp. 11-26
Author(s):  
Jae Hoon Lee ◽  
Young Sik Choi
Keyword(s):  
Cancer Patients ◽  
Fertility Preservation ◽  
Young Women ◽  
Large Scale ◽  
Ovarian Tissue ◽  
Gonadotropin Releasing Hormone ◽  
Ovarian Tissue Cryopreservation ◽  
Breast Cancer Patients ◽  
Ovarian Suppression ◽  
Releasing Hormone

Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.

Ovarian tissue cryopreservation and transplantation in patients with central nervous system tumours

2021 ◽  
Author(s):  
Thu Yen Thi Nguyen ◽  
Luciana Cacciottola ◽  
Alessandra Camboni ◽  
Joachim Ravau ◽  
Michel De Vos ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cancer Cells ◽  
Ovarian Tissue ◽  
Neuron Specific Enolase ◽  
Ovarian Tissue Cryopreservation ◽  
Malignant Cells ◽  
Ovarian Cortex ◽  
Cns Tumours ◽  
Tissue Cryopreservation

Abstract STUDY QUESTION Is there a possibility of reseeding cancer cells potentially present in frozen ovarian tissue from patients with central nervous system (CNS) tumours? SUMMARY ANSWER Malignancy reseeding in cryopreserved ovarian tissue from 20 patients with CNS tumours was not detected by histology, immunohistochemistry (IHC), molecular biology or xenotransplantation. WHAT IS KNOWN ALREADY Ovarian metastasis potential has been documented in patients with leukaemia, borderline ovarian tumours, advanced breast cancer and Ewing sarcoma. However, data on the safety of transplanting frozen-thawed ovarian tissue from cancer patients with CNS tumours are still lacking. STUDY DESIGN, SIZE, DURATION This prospective experimental study was conducted in an academic gynaecology research laboratory using cryopreserved ovarian cortex from 20 patients suffering from CNS tumours. Long-term (5 months) xenografting was performed in immunodeficient mice. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects enrolled in the study were suffering from one of six types of CNS tumours including medulloblastoma, ependymoma, primitive neuroectodermal tumours, astrocytoma, glioblastoma and germinoma. The presence of malignant cells was investigated with disease-specific markers for each patient in cryopreserved and xenografted ovarian tissue by histology, IHC via expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP and ENO2 gene amplification. MAIN RESULTS AND THE ROLE OF CHANCE Serial sections of cryopreserved and xenografted ovarian tissue from 20 patients showed no malignant cells by histology. All samples were negative for NSE and GFAP, although these neural markers were expressed extensively in the patients’ primary tumours. Analysis by RT-ddPCR revealed no cancer cells detected in cryopreserved and xenografted ovarian fragments from subjects with astrocytoma, ependymoma, glioblastoma or medulloblastoma. Taken together, the study found no evidence of malignancy seeding in frozen-thawed and xenotransplanted ovarian tissue from patients affected by CNS cancers. LIMITATIONS, REASONS FOR CAUTION This analysis cannot guarantee complete elimination of disseminated disease from all cryopreserved ovarian cortex, since we are unable to examine the fragments used for transplantation. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to be conducted in patients with CNS cancers undergoing ovarian tissue cryopreservation and transplantation, and clearly demonstrates no tumour seeding in their frozen-thawed and xenografted tissue. This information is vital for doctors to provide patients with meaningful and accurate advice on the possibilities and risks of ovarian tissue reimplantation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique–the Excellence of Science (FNRS–EOS), number 30443682 awarded to M.-M.D. and T.Y.T.N., FNRS grant number 5/4/150/5 and FNRS-PDR Convention grant number T.0077.14 awarded to M.-M.D., grant 2018-042 from the Foundation Against Cancer awarded to A.C., and private donations (Ferrero, de Spoelberch). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER N/A.

scholarly journals Multiple Approaches for Individualized Fertility Protective Therapy in Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
I. Demeestere ◽  
F. Moffa ◽  
F. Peccatori ◽  
C. Poirot ◽  
E. Shalom-Paz
Keyword(s):  
Cancer Patients ◽  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Major Field ◽  
New Interactions

In the last decade, fertility preservation has risen as a major field of interest, creating new interactions between oncologists and gynecologists. Various options, such as cryopreservation of ovarian tissue, have been developed and are currently routinely proposed in many centers. However, many of the options remain experimental and should be offered to patients only after adequate counseling. This paper addresses the efficiency and the potential of the different fertility preservation approaches.

O-191 Assessing the use of tumour-specific DARPin-toxin fusion proteins for ex vivo purging of cancer metastases from human ovarian cortex tissue fragments before autotransplantation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Eijkenboom ◽  
V Palacio-Castañeda ◽  
F A Groenman ◽  
D D M Braat ◽  
C C M Beerendonk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Fusion Proteins ◽  
Breast Cancer Cells ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
In Vitro Growth ◽  
Ovarian Cortex ◽  
Positive Breast Cancer

Abstract Study question Is it possible to eradicate cancer cells from ovarian cortex by using tumour-specific designed ankyrin repeat protein (DARPin)-toxin fusion proteins, without compromising the ovarian tissue? Summary answer Purging ovarian cortex ex vivo from experimentally induced breast cancer tumour foci is possible by tumour-targeted DARPin-toxin fusion proteins trough inhibition of protein synthesis. What is known already Ovarian tissue cryopreservation and autotransplantation is a successful technique for fertility restoration in cancer patients. The procedure is not without risk since malignant cells may still be present in the graft. Procedures to detect cancer cells render the tissue fragment useless for autotransplantation. Strategies to circumvent this problem such as in vitro maturation of follicles or the construction of artificial ovaries are pursued but are still experimental. Alternatively, we have shown ex vivo purging of ovarian cortex is possible by elimination of rhabdomyosarcoma after treatment with verteporfin. This allows treatment of cortex fragments before autotransplantation without compromising ovarian tissue integrity. Study design, size, duration Human ovarian cortex fragments harbouring breast cancer tumour foci were exposed for 24 h to DARPins fused to the translocation and catalytic domain of Pseudomonas aeruginosa exotoxin A (DARPin-toxin fusion proteins) targeting EpCAM or HER2. After treatment with the DARPin-toxin fusion proteins the tissue was cultured for an additional 6 days to allow any remaining tumour cells to form foci. In addition, the functional integrity of the ovarian tissue was analysed after purging. Participants/materials, setting, methods Breast cancer cell lines expressing different levels of EpCAM and HER2 were introduced in human ovarian tissue to form tumour foci. After purging with DARPin-toxin fusion proteins, the presence of any remaining cancer cells in the tissue was analysed with (immuno)histochemistry and RT-qPCR. Possible detrimental effects on the viability of ovarian cortex and follicles were determined by (immuno)histology, a follicular viability assay and an assay to determine the in vitro growth capacity of small follicles. Main results and the role of chance Ovarian cortex harbouring EpCAM-positive breast cancer cells showed a significant decrease in the number of tumour foci after treatment with the EpCAM-targeted DARPin-toxin fusion proteins. Although exposure to the EpCAM-specific DARPin had no effect on morphology or viability of follicles, a decrease in oocyte viability after in vitro growth experiments was observed, presumably due to low level expression of EpCAM on oocytes. In contrast to the EpCAM-specific DARPin-toxin fusion protein, the DARPin-toxin fusion protein targeting HER2 had no detrimental effects on morphology, viability or in vitro growth of follicles while foci of HER2-positive breast cancer cells were severely affected as indicated by the presence of apoptotic bodies, tumour cell remnants and the absence of viable tumour cells. The histological results after purging with the HER2-specific DARPin-toxin fusions proteins were confirmed by RT-qPCR, showing a decrease to basal levels of HER2 mRNA in the ovarian cortex tissue. Limitations, reasons for caution The effect of DARPin-toxin fusion proteins depends heavily on the expression of their target on the cancer cell. The target protein should not be expressed by ovarian cortex as this may lead to tissue damage. The functional integrity of ovarian cortex after the treatment requires further investigation in vivo. Wider implications of the findings Purging metastases from ovarian cortex without harming ovarian tissue is possible by targeting tumour specific surface expressed antigens with DARPin-toxin fusion proteins. Purging ovarian cortex tissue with DARPin-toxin fusion proteins provides a feasible therapeutic strategy to prevent reintroduction of cancer by autotransplantation in case of malignancies expressing tumour-specific surface markers. Trial registration number not applicable

O-180 Oocyte vitrification for fertility preservation does not delay the initiation of neoadjuvant chemotherapy for breast cancer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Sellami ◽  
M Grynberg ◽  
A Benoit ◽  
C Sifer ◽  
A Mayeur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Cancer Diagnosis ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Oocyte Retrieval ◽  
Breast Cancer Patients ◽  
Oocyte Vitrification

Abstract Study question Does oocyte vitrification for fertility preservation (FP) delay the initiation of neoadjuvant chemotherapy for breast cancer? Summary answer The indication of neoadjuvant chemotherapy for breast cancer should not be considered as an impediment to urgent oocyte vitrification for FP. What is known already FP is considered as one of the most important issues to address for young breast cancer patients. Cryopreservation of oocytes or embryos may be considered after controlled ovarian hyperstimulation (COH) or in vitro maturation (IVM). Pregnancies have been reported after reutilization of oocytes frozen following both procedures. Although oocyte competence is better after COH, this strategy requires on average 13 days to be achieved. In addition, the safety of ovarian stimulation before tumor removal is currently not formally established. In case of neoadjuvant chemotherapy, the risk-benefit balance of COH is not well known. Study design, size, duration Retrospective cohort study including all breast cancer patients eligible for oocyte vitrification following COH or IVM before initiation of neoadjuvant chemotherapy between January 2016 and December 2020. Participants/materials, setting, methods Inclusion criteria were: female patients with confirmed non metastatic breast cancer, 18 to 40 years of age, with indication of neoadjuvant chemotherapy, who have had oocyte retrieval for FP after COH or IVM +/- cryopreservation of ovarian tissue. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. Main results and the role of chance A total of 198 patients with confirmed breast cancer who had oocyte retrieval following COH (n = 57) or IVM +/- cryopreservation of ovarian tissue (n = 141) for FP prior to neoadjuvant chemotherapy were included. Although women in IVM group were significantly younger as compared to patients who underwent COH (31.7 ± 4.2 vs. 33.3 ± 4.0 years, p = 0.019), ovarian reserve parameters, BMI and cancer stage did not differ between the two groups. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COH or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36.9 ±13.5 days in COH and IVM groups respectively, p=0.857). Limitations, reasons for caution The time from referral to FP consultation may have influenced the type of FP. In addition, the retrospective nature of the present analysis may constitute a limitation. Moreover, the efficiency and security of the different FP strategies used has not been analysed. Wider implications of the findings Oocyte vitrification following COH or IVM was not associated with delayed breast cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Young patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. Trial registration number Not applicable

Young-onset colorectal cancer treatment side effects: Infertility, sexual dysfunction, and quality-of-life outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3587-3587
Author(s):  
Laura Diane Porter ◽  
Ronit Yarden ◽  
Kim Lynn Newcomer ◽  
Negeen Fathi ◽  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Side Effects ◽  
Sexual Dysfunction ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Cancer Treatments ◽  
Young Onset

3587 Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. Young-onset colorectal cancer refers to individuals diagnosed under the age of 50. In recent years, the incidence has increased by 2.2% annually in individuals younger than 50 years and 1% in individuals 50-64, in contrast to a 3.3% decrease in adults 65 years and older. Young-onset (YO) CRC patients and survivors face unique clinical challenges with fertility and sexual dysfunctions, but this risk is not well quantified. There is limited data and public discussion on the long-term effects of colorectal cancer treatments on fertility and sexual dysfunction and the long-term impact on the quality of life. Methods: To explore the unique challenges and unmet needs of the young-adult patient population, a cross-sectional study was conducted. Colorectal cancer patients and survivors (N = 884) diagnosed between the ages of 20 to 50 years old (median age 42 ± 7.0) completed an online questionnaire based on established instruments EORTC-QOL-30, EORTC-CR-29, and EORTC-SHC-22. Results: Thirty-one percent of respondents stated that a medical professional spoke to them about fertility preservation at the time of diagnosis and during treatment. Only 31% were referred to a reproductive endocrinologist, even though 37% of women and 16% of men reported that treatment left them infertile or sterile. Among survey respondents, 12% of women had an egg retrieval procedure, and 36% of men had their sperm preserved prior to the start of treatment. Fifty-three percent of women reported treatment led to premature menopause. Sixty-five percent of respondents suffer from some level of sexual dysfunction due to treatment. In patients who received radiation therapy, women were 12% less likely than men to have discussed sexual side effects with the provider before treatment. Patients who have an ostomy reported more severe sexual dysfunction (17.8%). Rectal cancer patients were 2.5 times more likely than those with colon cancer to report severe dysfunction after their treatment. More than 25% of the respondents said they would have considered alternative treatment if they would have known the risks of sexual dysfunction. Conclusions: Our survey demonstrates inadequate communications between patients and providers about the irreversible fertility and sexual effects of colorectal cancer treatments. Younger patients and survivors face unique long-term challenges and require further information about fertility preservation options and emotional support regarding their sexuality post-treatment. Other studies are needed to assess the physical and psychological side effects endured by young-onset CRC patients and survivors.

scholarly journals Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity

2020 ◽  
Vol 21 (20) ◽  
pp. 7792
Author(s):  
Hyun-Woong Cho ◽  
Sanghoon Lee ◽  
Kyung-Jin Min ◽  
Jin Hwa Hong ◽  
Jae Yun Song ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Alkylating Agents ◽  
Survival Rates ◽  
Chemotherapeutic Agents ◽  
Reproductive Age ◽  
Experimental Techniques ◽  
Ovarian Tissue Cryopreservation

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient’s age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

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