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In recent years, more cancer patients are achieving long-term survival owing to advances in treatment. However, cancer treatment can cause gonadal dysfunction that leads to loss of fertility. Thus, it is important for clinical oncologists to consider fertility preservation in children, adolescents, and young adults with cancer who are expected to have a favorable outcome and may wish to have children in the future. Sometimes, fertility preservation has to be abandoned depending on the stage of the cancer and the general condition of the patient, because fertility preservation procedures may unacceptably delay cancer treatment or be too risky for the patient. The Clinical Practice Guidelines for Fertility Preservation in Children, Adolescents, and Young Adults with Cancer were published in 2017 as the first guidelines for this field in Japan. These guidelines cover general principles and recommendations for 8 oncological categories, which is a point of difference from other guidelines. Close coordination between clinical oncologists and reproductive medicine specialists is important over the long term from the pretreatment phase through the post-treatment phase. Therefore, the guidelines were devised to help medical staff consider the available fertility preservation therapies and determine whether performing fertility preservation is appropriate before initiating the treatment for cancer, and to ultimately improve survivorship for children, adolescents, and young adults with cancer. This article reviews the latest information concerning clinical practice guidelines around the world, including the American Society of Clinical Oncology guidelines that were the first to be published in this field.

In Japan, an important issue is to be able to provide young cancer patients with timely and accurate information about the indications and options for fertility preservation when it is applicable. Therefore, it is necessary to create an environment that assists young cancer patients to make a decision about whether or not to choose fertility preservation. The Japan Society for Fertility Preservation was established in 2012, as Japan's first oncofertility association. Its purpose is to create an environment in which cancer patients can receive evidence-based oncofertility care. Accordingly, the mantra of the Japan Society for Fertility Preservation is: 'While anticancer treatment should be prioritized, fertility preservation may also be chosen to allow the patient to fight cancer without losing hope of a normal future'.

Background As 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. Method The literature regarding OTT, which is currently under development, was reviewed. Main findings To 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. Conclusion Improving 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.

Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian diseases causing infertility. Although there is no effective treatment for POI, therapies for polycystic ovarian syndrome include ovarian wedge resection or laser drilling to induce follicle growth. Underlying mechanisms for these disruptive procedures are unclear. Here, we explored the role of the conserved Hippo signaling pathway that serves to maintain optimal size across organs and species. We found that fragmentation of murine ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. In addition to elucidating mechanisms underlying follicle growth elicited by ovarian damage, we further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then extended results to treatment of infertility in POI patients via disruption of Hippo signaling by fragmenting ovaries followed by Akt stimulator treatment and autografting. We successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro activation approach is not only valuable for treating infertility of POI patients but could also be useful for middle-aged infertile women, cancer patients undergoing sterilizing treatments, and other conditions of diminished ovarian reserve.

In vitro generation of hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) has the potential to provide novel therapeutic approaches for replacing bone marrow (BM) transplantation without rejection or graft versus host disease. Hitherto, however, it has proved difficult to generate truly functional HSCs transplantable to adult host mice. Here, we demonstrate a unique in vivo differentiation system yielding engraftable HSCs from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis. In mice, we found that iPSC-derived HSCs migrate from teratomas into the BM and their intravenous injection into irradiated recipients resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Using this in vivo generation system, we could demonstrate that X-linked severe combined immunodeficiency (X-SCID) mice can be treated by HSCs derived from gene-corrected clonal iPSCs. It should also be noted that neither leukemia nor tumors were observed in recipients after transplantation of iPSC-derived HSCs. Taken our findings together, our system presented in this report should provide a useful tool not only for the study of HSCs, but also for practical application of iPSCs in the treatment of hematologic and immunologic diseases.

Ovarian tissue cryopreservation by vitrification is an effective technique, but there are still many unresolved issues related to the procedure. The aim of this study was to investigate the optimal culture time of postwarmed ovarian tissues and their viability before ovarian tissue transplantation. The bovine ovarian tissues were used to evaluate the effect of postwarming culture periods (0, 0.25, 0.5, 1, 2, 5, and 24 h) in the levels of residual cryoprotectant, LDH release, ROS generation, gene and protein abundance, and follicle viability and its mitochondrial membrane potential. Residual cryoprotectant concentration decreased significantly after 1 h of culture. The warmed ovarian tissues that underwent between 0 and 2 h of culture time showed similar LDH and ROS levels compared with fresh nonfrozen tissues. The anti-Mullerian hormone transcript abundance did not differ in any of the groups. No increase in the relative transcript abundance and protein level of Caspase 3 and Cleaved-Caspase 3, respectively, in the first 2 h of culture after warming. On the other hand, an increased protein level of double stranded DNA breaks (gamma-H2AX) was observed in postwarmed tissues disregarding the length of culture time, and a temporary reduction in pan-AKT was detected in postwarming tissues between 0 and 0.25 h of culture time. Prolonged culture time lowered the percentage of viable follicles in warmed tissues, but it did not seem to affect the follicular mitochondrial membrane potential. In conclusion, 1–2 h of culture time would be optimal for vitrified-warmed tissues before transplantation. Summary Sentence For ovarian tissue cryopreservation by vitrification, the recommended culture time following warming is between 1 and 2 h before ovarian tissue transplantation. Graphical Abstract

Purpose To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). Methods This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Results Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35–37‐year‐old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Conclusion Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664). Approximately half of patients who undergo embryo transfer following embryo cryopreservation as fertility preservation have live births. The overall live birth rate per embryo transfer was 21.4%.

The use of poly (ADP-ribose) polymerase (PARP) inhibitors is expected to increase, but their effect on fertility is still unclear. The aim of this study was to investigate the effect of PARP inhibitors on ovarian function. In an in vitro study, cultures of ovaries and granulosa cells (GCs) exposed to the PARP inhibitor olaparib were evaluated by real-time RT-PCR, histological study, and hormone assays. In an in vivo study, mice were administered olaparib orally and evaluated via in vitro fertilization (IVF), follicle count, immunohistochemical staining, and real-time RT-PCR. In vitro, the gene expression of GC markers decreased in the olaparib-treated group. Olaparib also negatively affected estradiol production and the expression of GC markers in cultured GCs, with abnormal morphology of GCs observed in the treated group. The follicle number indicated depletion of follicles due to atretic changes in the treatment group, both in vitro and in vivo. Also, olaparib reduced the number of retrieved oocytes and the fertilization rate of IVF, but they recovered after 3 weeks of cessation. Our results indicate that olaparib is toxic to ovaries.

Ovarian tissue cryopreservation followed by transplantation may damage the ovaries, potentially impeding fertility restoration. The notable antioxidant properties of curcumin highlight its potential as a therapeutic agent for enhancing fertility restoration. The use of nano-curcumin to improve ovarian tissue transplantation outcomes after vitrification for fertility preservation remains unknown. This study aimed to evaluate endocrine function, by measuring estradiol (E2), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH), and ovarian follicle count in rats subjected to vitrification and transplantation. Thirty female rats were categorized into three groups ( n  = 10/group): control (Group 1), untreated (Group 2), and nano-curcumin treated (Group 3; 2 mg/kg/day for 14 days). The rats were euthanized, and blood samples and ovaries were collected for analysis. The FSH level in the treated group (0.99 (0.97-1.00) mIU/ml) was significantly lower compared to that in the other groups, with a significant difference, particularly against Group 2 ( p  < 0.05). E2 and AMH values were higher in the treated group, with increased primordial and total follicle counts, though not statistically significant ( p  = 0.069 and p  = 0.051). The administration of nano-curcumin may improve hormonal function and increase the number of follicles in rat ovaries after vitrification and transplantation.

Many patients visit dental clinics complaining of oral malodor. However, there is no simple, inexpensive tool for assessing oral malodor. Therefore, this study developed a simple method using a detector tube. A detector tube was created to detect hydrogen sulfide based on the color change of an indicator (GASTEC, Kanagawa, Japan). We confirmed the ability to detect hydrogen sulfide concentrations of 200 ppb, which corresponds to the human olfactory threshold, using standard gas. The hydrogen sulfide detector tube was used to evaluate oral malodor in 42 outpatients aged 16-80 years, and the results were compared with an organoleptic test (OLT) and volatile sulfur compound (VSC) concentrations measured using a portable sulfide monitor. Comparing the hydrogen sulfide detector tube with the OLT score, the sensitivity was 0.90 and the specificity was 0.74 for OLT score ≧2.75 (  = 37). For VSC concentrations measured by the sulfide monitor, the sensitivity was 0.85 and the specificity was 1 at ≧300 ppb (  = 41). For OLT score ≧2.75 or VSC ≧300 ppb, which are considered indicators of \"clearly noticeable oral malodor,\" the detector tube showed a sensitivity of 0.84 and a specificity of 1. The diagnostic performance of the detector tube decreased when evaluating mouth air rather than standard gas, possibly due to the inhibitory effects of humidity and other gases in mouth air. Although it did not correspond to the olfactory threshold, the detector was highly sensitive and specific for determining the level of \"clearly noticeable oral malodor\"; it was considered a practical, easy-to-use tool. The new hydrogen sulfide detector tube, when used in combination with OLT, should be useful for determining \"clearly noticeable oral malodor\".