Fertility In Young Cancer Patients Research Articles

Fertility Preservation in Children and Adolescents during Oncological Treatment-A Review of Healthcare System Factors and Attitudes of Patients and Their Caregivers.

Oncofertility is any therapeutic intervention to safeguard the fertility of cancer patients. Anti-cancer therapies (chemotherapy, radiation therapy, etc.) entail the risk of reproductive disorders through cytotoxic effects on gamete-building cells, especially those not yet fully developed. This literature review analyzes the available data on securing fertility in pediatric and adolescent populations to identify the methods used and describe aspects related to financing, ethics, and the perspective of patients and their parents. Topics related to oncofertility in this age group are relatively niche, with few peer-reviewed articles available and published studies mostly on adults. Compared to pubertal individuals, a limited number of fertility preservation methods are used for prepubertal patients. Funding for the procedures described varies from country to country, but only a few governments choose to reimburse them. Oncofertility of pediatric and adolescent patients raises many controversies related to the decision, parents' beliefs, having a partner, ethics, as well as the knowledge and experience of healthcare professionals. As the fertility of young cancer patients is at risk, healthcare professionals should make every effort to provide them with an opportunity to fulfill their future reproductive plans and to have a family and offspring. Systemic solutions should form the basis for the development of oncofertility in pediatric and adolescent populations.

National oncofertility registries around the globe: a pilot survey.

Oncofertility is an emerging discipline which aims to preserve fertility of young cancer patients. As fertility preservation services have become increasingly available to cancer patients in many countries around the globe, it is crucial to establish a foundation of collaborative reporting to continuously monitor and assess oncofertility practices. This survey study investigates the current global landscape of official national oncofertility registries, a vital tool which allows for surveillance of the field. An online pilot survey was conducted to give the opportunity to report official national oncofertility registries available in 2022. Survey questions covered the availability of official national registries for oncofertility as well as the official national registries for cancer and assisted reproductive technologies. Participation in the survey was voluntary, anonymous and for free. According to our online pilot survey, responses were collected from 20 countries including Argentina, Australia, Brazil, Canada, Chile, China, Egypt, Germany, Greece, India, Japan, Kenya, Philippines, Romania, South Africa, Thailand, Tunisia, UK, USA & Uruguay. Only 3 out of the 20 surveyed countries have well-established official national oncofertility registries; and include Australia, Germany & Japan. The Australian official national oncofertility registry is part of Australasian Oncofertility Registry that also includes New Zealand. The German official national oncofertility registry is part of FertiPROTEKT Network Registry for German speaking countries that also includes Austria & Switzerland. The Japanese official national oncofertility registry includes Japan only and called Japan Oncofertility Registry (JOFR). A supplementary internet search confirmed the aforementioned results. Therefore, the final list of countries around the globe that have official national oncofertility registries includes Australia, Austria, Germany, Japan, New Zealand, and Switzerland. Some other countries such as the USA and Denmark are on their way to establish official national registries for oncofertility care. Although oncofertility services are expanding globally, very few countries have well-established official national oncofertility registries. By reviewing such a global landscape, we highlight the urgent need for having a well-established official national oncofertility registry in each country to monitor oncofertility services in a way that best serves patients.

P–442 Cancer does not adversely affect oocyte maturation in vitro with the exception of breast cancer

Abstract Study question Do different types of cancer affect the success of oocyte maturation in vitro compared to infertile women included in the in vitro fertilization (IVF) program? Summary answer Cancer does not adversely affect oocyte maturation in vitro, with the exception of breast cancer, compared to infertile women in the in vitro fertilization program. What is known already Vitrification and storage of oocytes in liquid nitrogen is one of the real options for maintaining reproductive function in cancer patients. Despite careful hormonal stimulation of the ovaries, however, the proportion of oocytes is immature and lost to the patient. In vitro maturation of oocytes can play an important role in resolving immature oocytes and increasing the chances of conception in cancer patients. Moreover, it can mean a safe way to store oocytes when ovarian hormonal stimulation could worsen the disease. Therefore, the aim of this study was to determine whether different types of cancer affect oocyte in vitro maturation. Study design, size, duration After ovarian stimulation in 18 cancer patients, the number and maturity of oocytes were compared to 21 infertile patients in the IVF program over a three-year period. In both groups, 119 germinal vesicle-GV oocytes were matured in vitro to compare the maturation rate. After IVF in a subset of 17 infertile patients, the fertilization of in vitro and in vivo matured oocytes was compared in the same cycles. The procedure was considered in cancer patients. Participants/materials, setting, methods In this prospective study, forty-five GV oocytes in cancer patients and 74 GV oocytes in infertile patients underwent in vitro maturation procedure. Each oocyte was matured in vitro in the MediCult IVM System by conditioning in LAG medium and maturation for up to 28 hours in IVM medium with added hormones FSH and hCG, in coculture with cumulus cells from mature oocytes in the same patients. Oocytes were fertilized by intracytoplasmic sperm injection (ICSI). Main results and the role of chance After controlled ovarian hormonal stimulation, 198 oocytes were retrieved in cancer patients and 259 oocytes in infertile women and there were no significant differences in the number of retrieved oocytes, proportion of degenerated oocytes and proportion of GV oocytes. In cancer patients, the proportion of oocytes that matured in vitro was lower than in infertile patients (66.0 vs. 80.0%), but the difference was not significant. Among cancer patients, the oocyte maturation rate tended to be lower in patients with breast cancer than in patients with other cancers (54.5% vs. 81.2%; difference not significant). However, in patients with breast cancer, significantly fewer oocytes matured in vitro than in infertile patients (54.5% vs. 80.0%; P < 0.05, Chi-Square test) even though they tended to be younger (29.3 ± 7.4 vs. 33.4 ± 5.0 years; non-significant difference). After in vitro maturation, there was a 13% increase in mature oocyte yield in cancer patients and a 20.1% increase in infertile women with no significant difference observed. After ICSI in a subset of infertile women, there was approximately the same fertilization rate between oocytes matured in vitro and in vivo (55.1% vs. 57.0%) in the same cycles. Limitations, reasons for caution For ICSI in oocytes matured in vitro, we had to use semen collected the day before, while oocytes matured in vivo were fertilized with fresh semen in the same cycle. Therefore, we could not compare the development of embryos in both groups. Wider implications of the findings: In vitro maturation of oocytes in connection with their vitrification or vitrification of embryos after their fertilization appears to be a valuable way to maintain the fertility of young cancer patients, but a worse outcome is expected in breast cancer patients. Trial registration number National Medical Ethical Committee Approval, No. 0120–222/2016–2; KME 115/04/16.

Resveratrol attenuates doxorubicin-induced meiotic failure through inhibiting oxidative stress and apoptosis in mouse oocytes.

Doxorubicin (DXR), a widely used chemotherapeutic drug, has adverse effects on female fertility in young cancer patients. However, the underlying mechanisms of doxorubicin exposure on female fertility and how to prevent it have not been well studied yet. Here, mouse oocytes were employed to investigate the issues mentioned above. The results showed that doxorubicin treatment impaired oocyte meiotic maturation by destroying spindle assembly and chromosome arrangement. In addition, doxorubicin caused oxidative stress by increasing reactive oxygen species (ROS) levels. Furthermore, doxorubicin led to severe DNA damage in oocytes, which eventually induced apoptosis through DNA damage-P63-Caspase3 pathway. Conversely, resveratrol (RES) effectively improved oocyte quality by restoring spindle and chromosome configuration, reducing ROS levels and inhibiting apoptosis. In summary, our results indicate that RES can protect oocytes against doxorubicin-induced damage.

Probing lasting cryoinjuries to oocyte-embryo transcriptome.

Clinical applications of oocytes cryopreservation include preservation of future fertility of young cancer patients, substitution of embryo freezing to avoid associated legal and ethical issues, and delaying childbearing years. While the outcome of oocyte cryopreservation has recently been improved, currently used vitrification method still suffer from increased biosafety risk and handling issues while slow freezing techniques yield overall low success. Understanding better the mechanism of cryopreservation-induced injuries may lead to development of more reliable and safe methods for oocyte cryopreservation. Using the mouse model, a microarray study was conducted on oocyte cryopreservation to identify cryoinjuries to transcriptionally active genome. To this end, metaphase II (MII) oocytes were subjected to standard slow freezing, and then analyzed at the four-cell stage after embryonic genome activation. Non-frozen four-cell embryos served as controls. Differentially expressed genes were identified and validated using RT-PCR. Embryos produced from the cryopreserved oocytes displayed 200 upregulated and 105 downregulated genes, associated with the regulation of mitochondrial function, protein ubiquitination and maintenance, cellular response to stress and oxidative states, fatty acid and lipid regulation/metabolism, and cell cycle maintenance. These findings reveal previously unrecognized effects of standard slow oocyte freezing on embryonic gene expression, which can be used to guide improvement of oocyte cryopreservation methods.

Long term results with vitrification compared to slow freeze of ovarian tissue

To determine the best method of freezing, and report overall duration of function and live baby rate, after ovary tissue freeze and transplant for young cancer patients. 13 patients over an eight year period underwent thaw and transplantation of ovarian tissue that had been frozen up to 19 years earlier, with detailed follow-up of hormones, menstruation, pregnancies, and birth. Seven had undergone slow freeze, and 6 had undergone vitrification. All cancer patients varying from age 18 to age 31 who returned with POF to have their frozen ovary tissue transplanted back from 10 years ago to 2 years ago (over an 8 year period) are included in this retrospective cohort study. Their ovary tissue was frozen from 19 years ago to 5 years ago. Slow freeze was used until 10 years ago, after which only vitrification was employed exclusively. We now have long term follow-up of these 13 cases, with monthly evaluation of hormones, cycling, pregnancy, and live birth rate, and we can compare the results of slow freeze cases with those who had undergone vitrification. A total of 90 patients have undergone ovary tissue freeze, but only 13 have returned for the transplant. All patients had return of ovarian function from 4 to 5 months post-op. In all cases the return of function was accompanied by a very sharp rise in AMH for 4 months, with a subsequent decline to low levels. 8 of the 13 are still functioning. Duration of function varied from 561 days to 1,641 days (this graft is still functioning). Five of the 13 are still functioning for over 3 ½ years. There are 9 healthy babies (69%) from 10 pregnancies (76%). Slow freeze resulted in 5 healthy babies out of 7 transplants. Vitrification resulted in 4 healthy babies out of 6 transplants. However slow freeze cases had a shorter duration of function (614 to 1155 days) and 5 of the 7 are no longer functioning, whereas vitrification cases are all still functioning over 3 ½ years (1281 days to 1641 days). Ovary tissue freezing is a robust method for preserving fertility in young cancer patients. Slow freeze yields pregnancy results equivalent to vitrification. However vitrified transplants have a longer duration of function, verifying our in vitro report earlier of higher oocyte survival with vitrification compared to slow freeze.

Review of the Different Treatments and Management for Prostate Cancer and Fertility

To compare the options available for prostate cancer management and their consequences on fertility for men, in order to best advise these men to choose their treatment, especially if they are young, with no child with their current partner. A literature review on prostate cancer and fertility over the last 26 years was carried out on PubMed database. The literature was based on evidence and practical considerations. Twenty-nine articles were selected according to their relevance. After prostatectomy, there is an obstructive infertility in 100% of the cases. In external radiotherapy, doses more than 15 cGy induced reduction in sperm count. Direct irradiation between 15 and 35 cGy caused oligozoospermia and doses between 35 and 50 cGy caused reversible azoospermia. The calculated projected doses on testicles were 196 cGy (± 145 cGy). The brachytherapy effects on fertility seems to be less harmful. The irradiation dose received by testicles is less important (less than 20 cGy) after brachytherapy than after external radiotherapy. Infertility induced by hormonal therapy alone should be reversible. Fertility and focal therapy have not been well evaluated yet. Active surveillance is the management of prostate cancer which allows to keep at best men's fertility. Urologists should consider approaching the topic of infertility when discussing the pros and cons of various prostate cancer management with their younger patients. If a patient with prostate cancer expresses interest in future fertility, a semen analysis should be performed. Cryopreservation represents the only preemptive accompanying possibility to preserve fertility in young cancer patients.

C-16: Human oocyte cryopreservation: Current status and outlook

Human oocyte cryopreservation is desired to preserve future fertility of young cancer patients, delay childbearing years, and avoid legal and ethical issues associated with embryo freezing. Unlike embryo freezing, oocyte cryopreservation has proved to be challenging due to susceptibility of oocytes to various cryoinjuries such as intracellular ice formation, disruption of cytoskeleton and spindle microtubules, premature exocytosis of cortical granules and zona hardening, parthenogenetic activation, and polyploidy. Although the first successful cryopreservation of human oocytes was reported in 1986, it took a decade of research and the use intracytoplasmic sperm injection to partially address some of the cryoinjuries and reproduce the initial success of human oocyte cryopreservation. Even then, the overall success rates were low and usually around 1–5%. These initial studies used slow cooling protocols. The first successful vitrification of human oocytes was achieved in 1999 with an overall success rate of ∼6%. Since then, considerably better results have been reported using both slow cooling and vitrification protocols. While the overall success rate after slow cooling still remains significantly lower than that of unfrozen controls, some fertility centers reported fertilization and pregnancy rates comparable to in vitro fertilization cycles using fresh oocytes after a vitrification approach that uses a minimal sample volume (

Oncofertility in Canada: cryopreservation and alternative options for future parenthood

Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, these fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. This article reviews fertility preservation options that use cryopreservation techniques. It also outlines some of the alternative options for future parenthood. Cryopreservation of a woman's gametes and gonadal tissue may involve embryo, oocyte, and ovarian tissue cryopreservation with or without ovarian stimulation. Similarly, male gametes and gonadal tissue may be cryopreserved. Techniques and success rates continue to improve. Third-party assistance through gamete donation, gestational carriers, and adoption are also alternative options for parenthood. Cryopreservation techniques are especially feasible options for fertility preservation in the newly diagnosed cancer patient.

Oxygen consumption rate of early pre-antral follicles from vitrified human ovarian cortical tissue.

The study of human ovarian tissue transplantation and cryopreservation has advanced significantly. Autotransplantation of human pre-antral follicles isolated from cryopreserved cortical tissue is a promising option for the preservation of fertility in young cancer patients. The purpose of the present study was to reveal the effect of vitrification after low-temperature transportation of human pre-antral follicles by using the oxygen consumption rate (OCR). Cortical tissues from 9 ovaries of female-to-male transsexuals were vitrified after transportation (6 or 18 h). The follicles were enzymatically isolated from nonvitrified tissue (group I, 18 h of transportation), vitrified-warmed tissue (group II, 6 and 18 h of transportation) and vitrified-warmed tissue that had been incubated for 24 h (group III, 6 and 18 h of transportation). OCR measurement and the LIVE/DEAD viability assay were performed. Despite the ischemic condition, the isolated pre-antral follicles in group I consumed oxygen, and the mean OCRs increased with developmental stage. Neither the transportation time nor patient age seemed to affect the OCR in this group. Meanwhile, the mean OCR was significantly lower (P < 0.05) in group II but was comparable to that of group I after 24 h of incubation. The integrity of vitrified-warmed primordial and primary follicles was clearly corroborated by the LIVE/DEAD viability assay. These results demonstrate that the OCR can be used to directly estimate the effect of vitrification on the viability of primordial and primary follicles and to select the viable primordial and primary follicles from vitrified-warmed follicles.

64 EX VIVO CULTURE OF FRESH AND FROZEN - THAWED SHEEP WHOLE OVARIES

Cryopreservation and retransplantation of ovarian tissue is a real option to preserve fertility in young cancer patients. However, a high risk of retransmission of malignancy exists in several tumours. In these patients, cryopreserved whole ovaries could provide an appealing source of oocytes to be grown and matured in vitro. The aim of this study was to develop a perfusion system for ex vivo culture of fresh and cryopreserved whole ovaries. Upon arrival to the laboratory, all ovaries were perfused via the ovarian artery with Ringer's solution and 10 UI L–1 of heparin for 10 min. Ovaries to be frozen were subsequently perfused with cryoprotectant solution [L-15 medium, 10% FBS, and 1.5 M dimethyl sulfoxide (DMSO)] and then frozen using Multi Thermal Gradient freezing technology (Core Dynamics Ltd., Ness Ziona, Israel), pushing the samples along the thermal gradient (4 to –70°C) at 0.01 mm s–1, resulting in a cooling rate of 0.3°C min–1. Samples were thawed at 37°C and immediately perfused with L-15 medium supplemented with decreasing sucrose concentrations (0.25, 0.125, and 0 M). In a closed-circuit perfusion system, 100 mL of recirculating medium (M199, 25 mM HEPES, 1% BSA, 2 mM glutamine, and antibiotic/antimycotic) was pumped into the ovarian artery using a peristaltic pump. The flow rate through the ovary was maintained between 1 and 1.5 mL min–1. Whole sheep ovaries were cultured at 38.5°C for 1 or 3 days. After culture, ovaries were fixed with 10% formaldehyde. Statistical analysis was performed using Student's t-test (SPSS 20, IBM Corp., Armonk, NY, USA). Morphological analysis showed that the rate of intact follicles was inversely related to the days of culture but was not affected by cryopreservation. In fact, the percentage of morphologically normal follicles in fresh and frozen ovaries cultured for 1 day (87 ± 3.4 and 83 ± 3.2%, respectively; P = 0.058) was higher (P = 0.048) than in ovaries cultured for 3 days (75 ± 2.9 and 71 ± 2.8%, respectively; P = 0.053). Cell proliferation, measured as Ki67-positive stromal cells, decreased during culture (P = 0.028) and was affected by cryopreservation both on Day 1 (13 ± 7 v. 15 ± 4%; P = 0.047) and Day 3 (10 ± 4 v. 12 ± 6%; P = 0.039). Similar results were observed for the apoptotic index that increased during culture both in fresh and cryopreserved ovaries (P = 0.028). The number of apoptotic cells per millimeter squared was lower (P = 0.031) in fresh (23 ± 10%) than in frozen ovaries (27 ± 15%) both on Day 1 and on Day 3 (30 ± 14 v. 33 ± 20%, respectively; P = 0.03). Cell viability and active endocrine function during culture is confirmed by steroid secretion, which is conserved in both fresh and cryopreserved ovaries for up to 3 days. Our results show that it is possible to culture both fresh and cryopreserved whole ovaries for up to 3 days. Although fresh ovaries, on average, did better than cryopreserved ones, we observed large individual variations, with positive and negative results overlapping between fresh and frozen samples. Further studies are in progress to explain the reason of such variations. Supported by AIRC IG 10376, Carraresi Foundation, and by Legge 7 (R.A.S).

Oncofertility in Canada: Gonadal Protection and Fertility-Sparing Strategies

Background: Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. Methods: Here, we review the fertility preservation measures currently available. Medical and surgical strategies are both outlined. Results: Fertility-preserving strategies and gonadal protection have demonstrated variable success in a number of approaches. The value of hormone suppression is still in question for women. Progestins for endometrial cancer and alternative chemotherapies are other medical approaches. Gonadal shielding and protective surgical approaches have also been attempted. Conclusions: The techniques discussed here may be selectively considered and integrated into patient care in an attempt to preserve future fertility before initiating cancer treatment.

Oncofertility in Canada: An Overview of Canadian Practice and Suggested Action Plan

Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, these fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. Here, we describe the services currently available in Canada and the challenges associated with their utilization. Finally, we outline strategies to help maximize and facilitate fertility preservation in the young cancer patient. Despite an existing infrastructure to the oncofertility system in Canada, the ability of that system's components to function together and to coordinate patient care is a challenge. Areas of weakness include poor access and referral to fertility services, a lack of readily available education for patients and health care providers, and inconsistent interdisciplinary coordination in patient care. The implementation of a framework for multidisciplinary resource allocation, education, patient referral, and established lines of communication may facilitate a functional oncofertility system in Canada.

Oncofertility in Canada: The Impact of Cancer on Fertility

Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, these fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. In this article, we review the gonadotoxic effects of cancer treatment on young men and women of reproductive age. The detrimental effects of cancer on fertility can be severe and may vary depending on the chemotherapy, radiotherapy, or surgical treatments involved. Fertility preservation should be addressed in an effort to mitigate the gonadal damage that may come with cancer therapy.

Healthy twins delivered after oocyte cryopreservation and bilateral ovariectomy for ovarian cancer

Anti-neoplastic treatments have significantly increased the survival of cancer patients, but female patients risk premature menopause. Oocyte cryopreservation has been proposed as a fertility-saving option. This report describes the first live birth achieved with autologous cryopreserved oocytes in an ovariectomized borderline cancer patient. A patient with a borderline ovarian tumour asked for oocyte cryopreservation after a right adnexectomy. Ovulation induction resulted in the retrieval and cryopreservation of seven mature oocytes. Thirty-nine months after a left ovariectomy, the patient asked for oocyte thawing and embryo transfer. Endometrial growth was induced using hormone replacement treatment. Three of the seven cryopreserved oocytes were thawed; they survived and, after insemination, normal fertilization took place. Three embryos were transferred into the patient's uterus. A twin pregnancy was achieved with the birth of two healthy females. Oocyte cryopreservation may be a reliable option for preserving fertility in young cancer patients who risk premature menopause due to surgery, chemotherapy or radiotherapy.

Successful Cryopreservation of Mouse Oocytes by Low Concentrations of Trehalose and Dimethylsulfoxide

Oocyte cryopreservation may avoid some complications of human embryo freezing and preserve future fertility of young cancer patients. However, oocyte cryopreservation is still an experimental procedure, and there is a need for alternative approaches. In nature, various organisms effectively use sugars such as trehalose to undergo anhydrobiosis and cryobiosis. By overcoming the permeability barrier of cell membranes, we have previously shown that when present inside and outside of the cell, trehalose, a non-reducing sugar, protects mammalian cells including human and mouse oocytes against freezing-associated stresses.

Preserving Fertility In Young Cancer Patients

Preserving Fertility In Young Cancer Patients

Fertility preservation for children treated for cancer (1): scientific advances and research dilemmas

Most children treated for cancer can now expect to be cured and to be fertile. However, in a significant minority, future fertility may be compromised by their disease or its...