Methods for preserving fertility in young women suffering from cancer: some aspects of ovarian tissue cryopreservation (original) (raw)
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Human Reproduction, 2019
STUDY QUESTION: Does first-line chemotherapy affect the quality of ovarian pre-antral follicles and stromal tissue in a population of young patients? SUMMARY ANSWER: Exposure to first-line chemotherapy significantly impacts follicle viability, size of residual intact follicles, steroid secretion in culture and quality of the stromal compartment. WHAT IS KNOWN ALREADY: First-line chemotherapy is considered to have a low gonadotoxic potential, and as such, does not represent an indication for fertility preservation. Studies investigating the effects of chemotherapy on the quality of ovarian tissue stored for fertility preservation in young patients are limited and the results sometimes contradictory. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study including young patients referred to three centers (Helsinki, Oslo and Tampere) to perform ovarian tissue cryopreservation for fertility preservation between 2003 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 43 patients (age 1-24 years) were included in the study. A total of 25 were exposed to first-line chemotherapy before cryopreservation, whereas 18 patients were not. Density and size of follicles divided by developmental stages, prevalence of atretic follicles, health of the stromal compartment and functionality of the tissue in culture were evaluated and related to age and chemotherapy exposure. Activation of dormant follicles and DNA damage were also assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Patients exposed to first-line chemotherapy showed a significantly higher density of atretic primordial and intermediary follicles than untreated patients. The intact primordial and intermediary follicles were significantly smaller in size in patients exposed to chemotherapy. Production of steroids in culture was also significantly impaired and a higher content of collagen and DNA damage was observed in the stromal compartment of treated patients. Collectively, these observations may indicate reduced quality and developmental capacity of follicles as a consequence of first-line chemotherapy exposure. Neither increased activation of dormant follicles nor elevated levels of DNA damage in oocyte nuclei were found in patients exposed to chemotherapy.
Cryopreservation and culture of human primordial and primary ovarian follicles
Molecular and Cellular Endocrinology, 2000
Cryopreservation of ovarian cortical tissue containing high numbers of primordial and primary follicles would benefit young women who are going to undergo chemotherapy or radiotherapy, or anticipated premature ovarian failure. Human ovarian tissue has been successfully cryopreserved using dimethyl sulphoxide, propanediol and ethylene glycol as cryoprotectants. The viability after thawing has been shown morphologically, using viability tests, by transplanting the tissue to immunodeficient mice, and by culturing them in vitro. Maturation of oocytes in in vitro cultures from early follicles would be better than replantation for girls with malignancies which could be replanted with the tissue. For the time being we have managed to culture cryopreserved human primordial and primary follicles to secondary, and occasionally to early antral stages in organ culture within slices of cortical tissue in extracellular matrix. The culture conditions have to be improved to get systematically early antral follicles for a second step of maturation of cumulus-oocyte-complexes.
Ovarian Folliculogenesis in Mammals: A Qualitative and Quantitative Analysis
Indian Journal of Veterinary Anatomy, 2014
Female fertility depends on the supply and maturation of the ovarian germ cells, i.e., the oocytes, and the differentiation and proliferation of granulosa and theca cells. During prenatal life, the ovarian cortex increases as the ovigerous cords become more extensive, convoluted and elongated and contained germ cells and pregranulosa cells. The formation of primordial follicles first occurred at the cortico-medullary junction and migrated towards the periphery of cortex, however the other follicles appear at late gestation. Recent classification of follicular atresia as antral and basal type is equivalent to first and second degree of obliterative atresia, respectively. This review reports current knowledge and proposes novel hypotheses that can formulate the contribution of germ cells to ovarian differentiation and folliculogenesis.
Ovarian follicular dynamics: from basic science to clinical practice
Journal of Reproductive Immunology, 1998
The management of low responders (LR) to ovarian stimulation in cycles of assisted reproduction (AR) is a difficult challenge. Aging of the ovary and LR are coincidental in many situations, but LR is also present in young patients undergoing AR. In fact, today it is a recognized cause of infertility. When the aged ovary is considered, there is evidence that the functioning of the granulosa cells as well as the quality of the oocytes and resulting embryos are affected. Similarly, in young LR, the production of inhibin is affected. However, there is no evidence that the quality of the oocyte and/or the resulting embryo is affected. In this study, we have retrospectively analyzed our files and observed that the quality of the oocytes and embryos was similar between younger and older LR and normal responders (NR). Studies using color Doppler vaginal ultrasound have shown that the pulsatility index (PI) and the resistance index (RI) were increased in LR as compared with NR, suggesting that there was some degree of vascular resistance to flow. Treatment of LR is also a difficult challenge. Ovum donation is a successful treatment for LR, since cumulative birth rates are \ 85% with four attempts of embryo transfer. The future may be promising for LR once new technologies are introduced into clinical practice. The use of recombinant gonadotropins and genetically engineered human gonadotropin derivatives may be of considerable help for LR. Similarly, non-gonadotropin hormones, such as cytokines or growth factors, may be shown to play a role in the stimulation of the ovary in the near future, and may therefore open new frontiers for treatment of LR.
Oocyte collection during cryopreservation of the ovarian cortex
Fertility and Sterility, 2003
Intensive chemotherapy and radiotherapy improve long-term survival in young women with cancer. However, these treatments lead to severe depletion of the follicular reserve. In addition, women who undergo bone marrow transplantation have a very high risk for ovarian failure, causing premature menopause and infertility.