Fertility Preservation Strategies Research Articles

Oncofertility: Pharmacological Protection and Immature Testicular Tissue (ITT)-Based Strategies for Prepubertal and Adolescent Male Cancer Patients.

While the incidence of cancer in children and adolescents has significantly increased over the last decades, improvements made in the field of cancer therapy have led to an increased life expectancy for childhood cancer survivors. However, the gonadotoxic effect of the treatments may lead to infertility. Although semen cryopreservation represents the most efficient and safe fertility preservation method for males producing sperm, it is not feasible for prepubertal boys. The development of an effective strategy based on the pharmacological protection of the germ cells and testicular function during gonadotoxic exposure is a non-invasive preventive approach that prepubertal boys could benefit from. However, the progress in this field is slow. Currently, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells is offered to prepubertal boys as an experimental fertility preservation strategy by a number of medical centers. Several in vitro and in vivo fertility restoration approaches based on the use of ITT have been developed so far with autotransplantation of ITT appearing more promising. In this review, we discuss the pharmacological approaches for fertility protection in prepubertal and adolescent boys and the fertility restoration approaches developed on the utilization of ITT.

Propagation of Spermatogonial Stem Cell-Like Cells From Infant Boys

BackgroundGonadotoxic treatment of malignant diseases as well as some non-malignant conditions such as cryptorchidism in young boys may result in infertility and failure to father children later in life. As a fertility preserving strategy, several centers collect testicular biopsies to cryopreserve spermatogonial stem cells (SSCs) world-wide. One of the most promising therapeutic strategies is to transplant SSCs back into the seminiferous tubules to initiate endogenous spermatogenesis. However, to obtain sufficient numbers of SSC to warrant transplantation, in vitro propagation of cells is needed together with proper validation of their stem cell identity.Materials and MethodsA minute amount of testicular biopsies (between 5 mg and 10 mg) were processed by mechanical and enzymatic digestion. SSCs were enriched by differential plating method in StemPro-34 medium supplemented with several growth factors. SSC-like cell clusters (SSCLCs) were passaged five times. SSCLCs were identified by immunohistochemical and immunofluorescence staining, using protein expression patterns in testis biopsies as reference. Quantitative polymerase chain reaction analysis of SSC markers LIN-28 homolog A (LIN28A), G antigen 1 (GAGE1), promyelocytic leukemia zinc finger protein (PLZF), integrin alpha 6 (ITGA6), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and integrin beta 1 (ITGB1) were also used to validate the SSC-like cell identity.ResultsProliferation of SSCLCs was achieved. The presence of SSCs in SSCLCs was confirmed by positive immunostaining of LIN28, UCHL1 and quantitative polymerase chain reaction for LIN28A, UCHL1, PLZF, ITGA6, and ITGB1, respectively.ConclusionThis study has demonstrated that SSCs from infant boys possess the capacity for in vitro proliferation and advance a fertility preservation strategy for pre-pubertal boys who may otherwise lose their fertility.

Fertility preservation in Turner syndrome: Karyotype does not predict ovarian response to stimulation

Turner syndrome (TS) is responsible for gonadal dysgenesis with high risk of premature ovarian insufficiency. Little is known about fertility preservation (FP) strategies is this population. Data from women with TS consulting with a fertility specialist in our FP centre from 2014 to 2018 were retrospectively collected. Total number of mature oocytes cryopreserved using vitrification. Nine women with TS were referred. Three women with different karyotypes underwent controlled ovarian stimulation (COS) for oocyte vitrification. Mean age at TS diagnosis was 13.7years [9-20]. Mean referral delay between TS diagnosis and fertility consultation was 9.7years [7-14]. First counselling for FP was provided at 23.7years [18-28]. Mean AMH serum level prior to COS was 53.8pmol/L [3.6-95]. All three women succeeded in obtaining cryopreserved oocytes with a mean number of 15.3 per woman [9-20] and 9.2 per COS cycle [2-20]. Ovarian response to COS was unexpectedly remarkable for the woman with a complete 45,X monosomy. Procedure was well tolerated for all women. None of them have used oocytes for in vitro fertilization yet. Independently of karyotype, antral follicular count, AMH and FSH levels seemed to be reliable predictive markers of oocyte cryopreservation success. In a monosomic TS woman, cryptic ovarian mosaicism could explain a successful ovarian response to stimulation with a high number of retrieved oocytes. In case of spontaneous menarche, TS adolescents should be referred during transition to adulthood for FP counselling to avoid referral delay and limit time-related diminished ovarian reserve.

Fertility Preservation in Women with Endometriosis: It is About Time We Talk About it!

Endometriosis is a common benign disease that affects young women and carries a significant risk to the reproductive organs. Studies have shown that endometriosis is associated with diminished ovarian reserve and worse prognosis in assisted reproductive technology treatments. Surgical treatment aims to remove the disease while maintaining reproductive potential with minimal damage to the reproductive organs. The authors reviewed the published literature regarding fertility preservation in endometriosis, focussing on patient selection criteria, available treatment options, and follow-up. The goal of this study was to find evidence to answer the following clinical questions: how should women of reproductive age with endometriosis be managed, and what fertility-sparing options are available? Cryopreservation of embryos and mature oocytes are established techniques for preserving fertility in women during the reproductive period. Fertility preservation is a key consideration in the care of young girls and women with endometriosis, mainly those with ovarian endometriomas and advanced disease. Although no cohort studies have been published on the subject to date, adequate information detailing disease progression, treatment options, and the risks involved should be made available for these women. Available fertility preservation strategies include embryo and oocyte crypreservation, and women should be counselled individually on the risks, benefits, and costs involved with these options. In this scenario, management by a multidisciplinary endometriosis team is a fundamental step for producing successful results.

Fertility preservation strategies for rectal cancer in reproductive-age women.

Despite rectal cancer being unusual before 40, fertility preservation (FP) remains a major concern for these reproductive-age women. Treatment usually involves pelvic radiotherapy, neoadjuvant chemotherapy, and surgery of rectum and mesorectum resection, at high risk of impairing fertility in women with risks of premature ovarian failure and radio-induced uterus damage. To date, there is no consensus on FP strategy for rectal cancer. We shared experiences between oncofertility experts from a French research network Groupe de Recherche et d'Etude en Cryoconservation Ovarienne et Testiculaire about a case of rectal cancer in a young woman. Indications, advantages and disadvantages of different FP strategies were discussed: ovarian transposition, cryopreservation of ovarian cortex and oocyte vitrification. This case was the starting point that led to the development of a French multidisciplinary e-meeting for sharing experiences and for suggesting the best strategy when faced with a complex oncofertility case.

Fertility concerns, preservation strategies and quality of life in young women with breast cancer: Baseline results from an ongoing prospective cohort study in selected European Centers

ObjectivesMost research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns. Materials and methodsPatient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern. ResultsAmong 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039). ConclusionsYoung women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.

Fertility, sexuality and cancer in young adult women.

To provide an up-to-date overview on indications, efficacy and safety of the existing fertility preservation strategies as well as on the features and management of sexual dysfunction in young adult women with newly diagnosed cancer. Because of the improved life expectancy of cancer survivors, a growing attention should be given to the side effects of anticancer treatments. Among young cancer patients, risk of infertility and sexual dysfunction are of great concern. As advocated by guidelines, patients need to be thoroughly informed of potential side effects of treatment before starting them. On this regard, efforts should be made to improve the counseling of young adult patients around fertility and sexuality. Fertility preservation strategies should be properly and extensively explained to all young patients, weighting the pros and cons to choose the more appropriate options for each situation. In addition, discussing sexual dysfunction and delivering sexual rehabilitation for cancer survivors not only allows for renewal of sexual function but can also promote increased quality of life and help women create a new and satisfying chapter in their life for many years after cancer.

Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies.

Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability. A nationwide sample of US women diagnosed with breast cancer before age 45years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling. Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35years vs ≥40years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%). Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education.

Current state and future possibilities of ovarian tissue transplantation.

BackgroundAs a result of recent developments in cancer treatment, cancer survivorship and survivors' quality of life have been emphasized. Although ovarian tissue cryopreservation (OTC) is an experimental technique, it would be the sole technique for fertility preservation treatment for girls with malignant disease. Indeed, OTC requires ovarian tissue transplantation (OTT) for conception. As for OTC, there is room to investigate OTT. The present review focused on the current state and progress of OTT.MethodThe literature regarding OTT, which is currently under development, was reviewed.Main findingsTo improve the outcome of OTT, both efficacy and safety are important. Good surgical technique and the optimal site are important surgical factors, with orthotopic transplantation increasing. Treatment of growth factors, gonadotropins, antioxidants, apoptosis suppression factors, and cell therapy may improve the efficacy of OTT by inducing neo‐angiogenesis and preventing damage. Artificial ovaries, complete in vitro primordial follicle culture technique, and non‐invasive ovarian imaging techniques, such as optical coherence tomography, to select the best ovarian tissue are future possibilities.ConclusionImproving neo‐angiogenesis and preventing damage with optimization, as well as investigation of future techniques, may bring us to the next stage of a fertility preservation strategy.

Molecular effects on spermatozoa of Mytilus galloprovincialis exposed to hyposaline conditions.

Salinity represents a critical environmental and an ecological factor in the reproduction of marine species. As global climate changes and anthropogenic factors affect salinity, in this study, we have analyzed the responses of Mytilus galloprovincialis spermatozoa to hyposaline stress. We exposed mussels, in laboratory tanks, for 24 hr at 18°C to control (35.9 psu) and three hyposaline (17.1, 22.6, and 26.2 psu) conditions, and evaluated the expression of sperm hsp70 and protamine-like proteins genes. Further we analyzed the electrophoretic pattern, the DNA binding and the release from sperm nuclei of protamine-like proteins. For all experimental approaches used, the results obtained at 17.1 psu condition were very similar to those obtained in the control condition, while alterations were always recorded at 22.6 and 26.2 psu conditions. Particularly, at 22.6 and 26.2 psu, was observed: 42.5- and 17.1-fold increase in hsp70 expression, respectively, and hypoexpression of PL-II/PLIV protamine-like proteins genes. Further, electrophoretic mobility shift assays and salt-induced release of nuclear proteins from sperm nuclei, revealed alterations in the PL proteins/DNA binding, in these two hyposaline conditions. The similarity between the results obtained in control and in the more severe hyposaline condition (17.1 psu) could indicate a phenomenon of fertility preservation strategy due to gamete plasticity.

In Vitro Growth of Preantral Follicle and Maturation of Intrafollicular Oocyte from Aged Mice

This study aimed to recover the ovarian function through in vitro culture of preantral follicles from aged mice. First, we isolated the preantral follicles from ovaries of sixty-seven-week old B6D2F1 mice with decreased fecundity to know how many follicles were present in them, which was 6 preantral follicles including 2 primary, 2 early secondary and late secondary follicles from 8 aged mice. It was confirmed that a few follicles (~2) were present in aged mice through histological analysis compared to adult mice as control. The 9 days of in vitro culture of preantal follicles showed in vitro growth and induced maturation after treatment with hCG (2.5 IU/mL) and EGF (5 ng/mL). Cumulus cells in the cumulus-oocyte complexes (COCs) were removed using hyaluronidase and oocytes at the germinal vesicle (GV) and GV breakdown (GVBD) were obtained from preantral follicle culture of aged mice in vitro. In conclusion, these observations demonstrated that there still were a few preantral follicles in the ovaries of 67 week-old mice, which we were able to culture in vitro and oocytes were obtained from them. This study proposed an in vitro culture system using preantral follicle as a therapeutic strategy for fertility preservation in humans for assisted reproductive medicine.

Time from referral to ovarian tissue cryopreservation in a cohort of Danish women.

Young women with a cancer diagnosis often have very little time to decide whether or not to commence fertility-preserving strategies before initiating potentially sterilizing cancer treatment. Minimizing the interval from opting for fertility preservation to completion of the procedure will reduce the potential risk of delaying cancer treatment. In the current study, we have evaluated the period of time from referral to ovarian tissue cryopreservation (OTC) to actual freezing of the tissue in a cohort of Danish women. The study population comprised 277 consecutive patients with both malignant and nonmalignant diseases referred for OTC from four centers in the Danish network. Statistical analysis was conducted to analyze the impact of age, diagnosis, and referring center on the time from OTC-referral to OTC. A literature search for "random start" protocols for controlled ovarian stimulation (COS) for fertility preservation in cancer patients was performed. The time from OTC-referral to OTC was significantly influenced by diagnosis, age, and referring center. Women with malignant diseases other than breast cancer, such as sarcomas, pelvic cancers, and hematological cancers, experienced a significantly shorter interval to OTC (5days) than women with breast cancer (7days) and nonmalignant diseases including systemic, ovarian, and hereditary conditions (13-17.5days). Women over the age of 30years experienced a significantly longer time to OTC (P<0.03), and the diagnosis determined the length of the interval (P<0.001). According to the literature, fertility preservation by oocyte vitrification requires 13-14days, as the average time for 1 round of COS was 11days and oocyte collection can be performed 2days later. It is in the interest of both cancer patients and clinicians to perform fertility preservation as quickly and safely as possible. In a Danish setting, OTC provides a short interval of around 6days from the patient choosing this option to completion of the procedure. This is considerably less time than what is needed to perform COS and oocyte vitrification, and therefore OTC might be considered the preferred choice of fertility preservation when urgency is needed.

Oncofertility counselling in premenopausal women with HER2-positive breast cancer.

A complete oncofertility counselling should be offered to all premenopausal patients before the administration of anticancer treatments. This important discussion is a crucial step for allowing them to take fully informed decisions about the proposed therapy and its potential long-term consequences as well as on their need and interest of accessing the available strategies for ovarian function and/or fertility preservation. In premenopausal women with HER2-positive early breast cancer, limited evidence exists to counsel them about the potential added gonadotoxicity of targeted agents beyond the damage already caused by chemotherapy. In addition, the prognostic role of treatment-induced amenorrhea in this setting was unknown. In our exploratory analysis within the ALTTO (BIG 2-06) trial, we have recently described the rates of treatment-induced amenorrhea after chemotherapy plus trastuzumab and/or lapatinib and the prognostic value of developing this side effect according to the hormone receptor status of their tumours. We observed similar rates of treatment-induced amenorrhea in the four anti-HER2 treatment arms. The lack of an increased rate of treatment-induced amenorrhea in the dual anti-HER2 blockade arm suggests the possible gonadal safety of these agents. In addition, women with HER2-positive/hormone receptor-positive tumours showed significantly better survival outcomes if they developed treatment-induced amenorrhea, while no difference was observed for those with HER2-positive/hormone receptor-negative disease. Future research efforts are needed to address the gonadotoxicity of the new available targeted agents as well as to elucidate which is the best adjuvant endocrine therapy in premenopausal women with HER2-positive/hormone receptor-positive disease.

Sperm DNA Damage in Cancer Patients.

Fertility is a growing healthcare issue for a rising number of cancer survivors. In men, cancer itself and its treatment can negatively affect spermatogenesis by targeting the dividing spermatogonia and their cellular environment, ultimately leading to a reduction of testicular germ cells and sperm count. Experimental data and prospective longitudinal studies have shown that sperm production can recover after cancer treatment. But despite this, yet unpredictable, recovery in sperm production, cancer survivors are more at risk to produce sperm with aneuploidy, DNA damage, abnormal chromatin structure, and epigenetic defects even 2years post-treatment. Sperm DNA alteration is of clinical concern, as these patients may father children or seek assisted reproduction technologies (ART) using gametes with damaged genome that could result in adverse progeny outcomes. Interestingly, large cohort studies revealed lower birth rate but no significant impact on the health of the children born from male cancer survivors (naturally or using ART). Nevertheless, a better understanding of how cocktail of chemotherapy and new anticancer agents affect spermatogenesis and sperm quality is needed to reduce side effects. Moreover, developing new fertility preservation strategies is essential as sperm cryopreservation before treatment is currently the only option but does not apply for prepubertal/young postpubertal patients.

Antioxidant effects of quercetin in freeze-thawing process of mouse spermatogonial stem cells

Objective: To evaluate the antioxidant effect of quercetin on cell viability, reactive oxygen species (ROS) contents and apoptosis of cryopreserved mouse spermatogonial stem cells (mSSCs). Methods: mSSCs were isolated from neonate mice and cultivated in culture medium containing 30 μΜ quercetin for 48 h and then frozen for 2 weeks. After thawing, MTT assay was carried out to analyze the cell viability. Moreover, intracellular ROS levels were measured by flow cytometery and apoptosis was evaluated by detection of phosphatidylserine externalization assay and also real-time polymerase chain reaction. Results: Pre-treatment of mSSCs by 30 μΜ quercetin significantly decreased intracellular ROS content and apoptotic cell numbers and improved viability of mSSCs. Moreover, the gene expression of Bcl-2 and Bax significantly increased and decreased respectively after the freeze-thawing process. Conclusions: Pre-treatment of mSSCs with quercetin can improve cell viability and reduce apoptosis during freeze-thawing process. It can be a promising way to improve the quality and efficiency of cryopreservation protocols used in fertility preservation strategies.

Ovarian Function and Fertility Preservation in Breast Cancer: Should Gonadotropin-Releasing Hormone Agonist be administered to All Premenopausal Patients Receiving Chemotherapy?

Chemotherapy-induced premature ovarian insufficiency (POI) is one of the potential drawbacks of chemotherapy use of particular concern for newly diagnosed premenopausal breast cancer patients. Temporary ovarian suppression obtained pharmacologically with the administration of a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been specifically developed as a method to counteract chemotherapy-induced gonadotoxicity with the main goal of diminishing the risk of POI. In recent years, important clinical evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients, including women who are not interested in conceiving after treatment or that would not be candidates for fertility preservation strategies because of their age. Nevertheless, in women interested in fertility preservation, this is not an alternative to gamete cryopreservation, which remains as the first option to be offered. In this setting, temporary ovarian suppression with GnRHa during chemotherapy should be also proposed following gamete cryopreservation or to women who have no access, refuse, or have contraindications to surgical fertility preservation techniques. In this article, we present an overview about the role of temporary ovarian suppression with GnRHa during chemotherapy in breast cancer patients by addressing the available clinical evidence with the aim of identifying both the best candidates for the use of this strategy and the still existing gray zones requiring further investigation.

Fertility preservation in ovarian tumours.

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%–14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A–B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life.Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility.We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers.

38 Vitrification of prepubertal lamb spermatogonia using a novel vitrification system

Vitrification is a method extensively used for preserving oocytes and embryos and is also gaining acceptance for preserving gonadal tissue. Cryopreservation of spermatogonial stem cells is an applicable method for young males seeking fertility preservation before starting a treatment or can be a tool for genetic preservation of rare or high-value animals. The aim of this work was to evaluate the cryopreservation of testicular tissue from young lambs by vitrification using a new device named E.Vit (FertileSafe, Ness Ziona, Israel) that permits all cryopreservation procedures to be performed in straw. The new device consists of a 0.3-mL straw (Cryo Bio System, IMV, L’Aigle, France) with a capsule containing 50-µm pores inserted at one end. Testicular tissue extracts were prepared from testes of slaughtered lambs (n=10, 40 days old), opened by sagittal sectioning with a microblade and collecting small pieces of testicular tissue (1mm3) from the middle part of the rete testis. Three pieces of gonadal tissue were inserted into each E.Vit device. Each straw was sequentially loaded vertically in two 1.5-mL microtubes, which contained the following solutions: first, the equilibrating solution (7.5% dimethyl sulfoxide+7.5% ethylene glycol+20% FCS in TCM-199) for 6min, followed by 90min in the vitrification solution (18% dimethyl sulfoxide+18% ethylene glycol+0.5M Trehalose+BSA in TCM-199). After exposure to the equilibrating solution and vitrification solution, the solutions were removed and the straws were directly loaded into LN2. The warming procedure consisted of placing the straws directly into 5-mL tubes containing 100, 50, and 25% warming solution (1M sucrose in TCM-199+20% FCS) at 38.6°C for 5min each before arrival into the holding medium. Samples were recovered from the straws incubated at 38.6°C in 5% CO2 in air in TCM 199+5% FCS and evaluated at 0 and 2h post-warming for viability using trypan blue staining. Expression of a panel of specific genes (SOD2, HSP90b, BAX, POUF5/OCT4, TERT, CIRBP, KIF11, AR, FSHR) was analysed by real-time PCR in cryopreserved tissue in vitro cultured for 2h post-warming (2hV), in fresh controls immediately after tissue dissection (0hF), and after 2h of in vitro culture (2hF). The majority of cells survived after vitrification, although viability immediately after warming (0hV: 56%±1.45) or after 2h of in vitro culture (IVC) (2hV: 54±7%) was significantly lower compared with non-cryopreserved fresh controls (0hF: 89%±1.45; ANOVA P&amp;lt;0.05). Expression analysis showed specific patterns for the different genes. Notably, BAX transcript abundance was not affected by vitrification or IVC, indicating an acceptable level of stress for the cells. The genes HSP90b and CIRBP were down-regulated in 2hF but increased in 2hV, as expected. Expression of SOD1 and OCT4 was altered by vitrification but not by IVC. Conversely, expression of TERT, KIF11, and AR was affected by both IVC and cryopreservation (ANOVA P&amp;lt;0.05). This novel protocol for testicular tissue cryopreservation of prepubertal animals may be a promising strategy for fertility preservation and can contribute as a new approach in the development of large-scale biodiversity programs.

Study of the Awareness of Adoption as a Family-Building Option Among Oncofertility Stakeholders in Japan.

PurposeThe oncofertility decision tree was developed by the oncofertility consortium as a tool to support healthcare professionals and patients through the complicated process of deciding the most appropriate fertility preservation strategy for patients with cancer. Various strategies include oocyte retrieval, oocyte donation, use of a gestational carrier and adoption. However, differences in the cultural and legal landscape present serious barriers to utilizing some of these strategies in Japan.Patients and MethodsWe surveyed Japanese oncofertility stakeholders including 60 cancer survivors, 27 oncology facilities, 78 reproductive medicine facilities and 15 adoption agencies by a questionnaire to characterize awareness among oncofertility stakeholders in Japan about parenting options including adoption to inform work to establish guidelines for decision-making by cancer survivors in an oncofertility.ResultsOur results indicate that oncologists and reproductive endocrinologists in Japan have an insufficient understanding of adoption that prevents them from adequately informing their patients. Japanese cancer survivors self-describe a lack in confidence in finding a suitable partner and raising a child. Contrastingly, of the 9 adoption agencies which responded, no agency included being a cancer survivor as a criterion for disqualification and 4 of 9 (44%) adoption agencies reported at least 1 adoption to a cancer survivor in the last year.ConclusionOur work demonstrates that a cancer survivor’s medical history itself is not a hurdle to adoption and investment in patient-provider education could be a viable strategy to improve the utilization of adoption as a fertility preservation strategy in Japan.

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL, April 2018) - Part 2 with Recommendations on the Therapy and Follow-up of Endometrial Cancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.