Anti-Müllerian hormone for screening, diagnosis, evaluation, and prediction: A systematic review and expert opinions.

AIM: To present evidence-based recommendations for anti-Müllerian hormone (AMH) measurement as an ovarian reserve test. METHODS: A systematic literature search for the clinical utility of AMH was conducted in PubMed from its inception to August 2022 to identify studies, including meta-analyses, reviews, randomized controlled trials, and clinical trials, followed by an additional systematic search using keywords. Based on this evidence, an expert panel developed clinical questions (CQs). RESULTS: A total of 1895 studies were identified and 95 articles were included to establish expert opinions subdivided into general population, infertility treatment, primary ovarian insufficiency, polycystic ovary syndrome, surgery, and oncofertility. We developed 13 CQs and 1 future research question with levels of evidence and recommendations. CONCLUSION: The findings of the current systematic review covered the clinical utility of AMH including its screening, diagnosis, evaluation, and prediction. Although some clinical implications of AMH remain debatable, these expert opinions may help promote a better understanding of AMH and establish its clinical significance.

The study of the efficiency of in vitro maturation of ovarian tissue oocytes in pediatric patients.

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.

Bone Development and Regeneration 2.0.

Bone is an important tissue which is a structural body component, carrying out the roles of mechanical stress response and organ/tissue protection [...].

Oncofertility-related psycho-educational therapy for young adult patients with breast cancer and their partners: Randomized controlled trial.

BACKGROUND: A couples' psycho-educational program called Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy was created and its effect when provided before cancer treatment was examined. METHODS: This multicenter randomized controlled trial with nonmasking, parallel two-group comparison enrolled women aged 20 to 39 years with early-stage breast cancer and their partners. They were randomly assigned to receive O!PEACE (37 couples) or usual care (37 couples). Primary end points were cancer-related posttraumatic stress symptoms, symptoms of depression, and anxiety. Secondary end points were stress-coping strategies, resilience, and marital relationship. RESULTS: Women receiving psycho-educational therapy had significantly reduced Impact of Event Scale-revised version for Japanese scores (p = .011, ηp 2  =  = .089). For patients with Impact of Event Scale-revised version for Japanese scores at baseline ≥18.27, O!PEACE therapy improved these scores when compared with usual care (U = 172.80, p = .027, r = 0.258). A >5-point reduction was present in 59.3% and 30% of women in the O!PEACE therapy and usual-care groups, respectively. For partners, O!PEACE therapy significantly improved stress-coping strategies (95% CI, -0.60 to -0.05; p = .018, ηp 2  =  = .074) and escape-avoidance marital communication (95% CI, -0.33 to -0.08; p = .001, ηp 2  = .136). O!PEACE therapy significantly improved the partners' support (95% CI, 0.10-0.50; p = .001, ηp 2  = .127), the rate of receiving fertility preservation consultations, and knowledge levels. CONCLUSIONS: O!PEACE therapy before cancer treatment can improve posttraumatic stress symptoms, stress-coping behavior, and marital relationships. Larger sample sizes and longer term follow-up are required. PLAIN LANGUAGE SUMMARY: A psycho-educational program, the Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy program was developed and evaluated for women diagnosed with breast cancer and their partners. A multicenter randomized controlled trial showed that the O!PEACE psycho-educational therapy, with only two precancer treatment sessions, can reduce cancer-related posttraumatic stress symptoms and improve oncofertility knowledge and marital relationships in young adult patients with breast cancer. The therapy could also improve stress-coping strategies in marital communications with their partners. Couples may use O!PEACE psycho-educational therapy to consider fertility preservation and improve their psychosocial aspects.

The effect of aromatase inhibitor on controlled ovarian stimulation for oocyte cryopreservation in adolescent and young cancer patients.

AIM: To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. METHODS: This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. RESULTS: Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. CONCLUSION: The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.

Twenty-first century oocyte cryopreservation-in vitro maturation of immature oocytes from ovarian tissue cryopreservation in cancer patients: A systematic review.

OBJECTIVES: Our review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte-in vitro maturation. METHODS: A thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte-in vitro maturation as fertility preservation. RESULTS: The primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte-in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use. CONCLUSION: Our review proposed the potential application of ovarian tissue oocyte-in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.

Clinical outcome of embryo cryopreservation in Japanese breast cancer patients: pregnancy rates after transfer of thawed embryos.

PURPOSE: To examine pregnancy outcomes after cryopreserved embryo transfer (ET) in breast cancer patients and to investigate the effect of controlled ovarian hyperstimulation (COH) as well as that of aromatase inhibitor (AI) administration and of the random start (RS) ovarian stimulation method. METHODS: This retrospective study covered 126 patients who underwent embryo cryopreservation between 2010 and 2019. Thirty-one patients underwent frozen embryo transfer (FET), and we examined resulting pregnancy rates (PRs) and live birth rates (LBRs) in those who did and did not undergo COH and in relation to the AI and RS methods. RESULTS: PR and LBR per patient were higher among patients who underwent COH than among those who did not. PR per ET did not differ from that documented for non-cancer infertility patients, after adjustment for age. The PR and LBR did not differ between use and non-use of AI (27.8% vs 35.2%). In addition, there was no significant difference in the PR or LBR between RS and conventional start ovarian stimulation (33.3% vs 30.8%). No prenatal fetal abnormalities were observed in 8 cases (including 5 AI cases and 2 RS cases). CONCLUSIONS: This study showed that the outcome of FET after FP was equivalent to that seen in non-cancer patients. Further, neither use of AI nor the RS method influenced LBR. COH including use of AI and the RS method are useful in FP for collecting and freezing many embryos within a short period and for increasing the per patient LBR after cancer treatment.

Investigation of the optimal culture time for warmed bovine ovarian tissues before transplantation†.

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.

Shortening the duration between ovarian removal and cryopreservation helps preserve fertility and maintain ovarian reserve after transplantation in mice.

OBJECTIVE: To evaluate the effect of storage of ovaries before cryopreservation on long-term fertility and ovarian reserve after transplantation in mice. DESIGN: Experimental study. SETTING: University hospital. ANIMAL(S): C57BL/6J and C57BL/6J-Tg (CAG-GFP) female mice. INTERVENTION(S): Storage and cryopreservation of mouse ovaries. Long-term fertility analysis of mice transplanted with thawed ovaries. MAIN OUTCOME MEASURE(S): Estrous cycles, number of live births, ovarian weight, and follicular counts of ovarian grafts. RESULT(S): At the first mating 3 months after ovarian transplantation, the mean number of live births was 2.6 ± 0.6 in the control group (no storage); in the storage groups, the mean number of live births was 2.9 ± 0.7 after 4 hours, 1.3 ± 0.5 after 8 hours, 0.2 ± 0.2 after 12 hours, and 0.8 ± 0.5 after 24 hours of storage; the difference from the control group was significant in the 12-hour storage group. At the second mating 6 months after ovarian transplantation, the mean number of live births was 1.8 ± 0.6 in the control group and 2.4 ± 0.6 and 0.3 ± 0.2 in the 4- and 8-hour storage groups, respectively; no live births occurred in the 12- and 24-hour storage groups. Seven months after ovarian transplantation, the numbers of primordial, primary, early secondary, and late secondary follicles were significantly lower in the 8-, 12-, and 24-hour storage groups than in the control group. CONCLUSION(S): In mice, shortening the storage time of ovaries before cryopreservation preserved fertility and ovarian reserve after transplantation, indicating that human ovaries might be cryopreserved immediately after harvesting or transported as quickly as possible to a cryopreservation facility to allow young patients with cancer to preserve long-term fertility and ovarian reserve.

Cryopreservation of paediatric ovarian tissue with an updated version of the Edinburgh criteria for appropriate patient selection.

RESEARCH QUESTION: Are the revised patient selection criteria for fertility preservation of children and adolescents appropriate? DESIGN: A retrospective and prospective observational cohort study implemented at a university hospital approved for fertility preservation by an academic society. The characteristics of children and the process of fertility preservation consultation were investigated. Mortality, the longitudinal course of the endocrine profile and the menstrual cycle were confirmed in patients who underwent ovarian tissue cryopreservation (OTC) before the age of 18 years. RESULTS: Of the 74 children and adolescents referred for a fertility preservation consultation, 40 (54.1%) had haematological disease, which included patients with rare diseases. The mean age of patients was 11.1 ± 4.3 years (median 12 years, range 1-17 years). In accordance with the revised criteria, 31 (41.9%) patients had their ovarian tissue cryopreserved. Two out of 31 had complications after surgery (infection and drug allergy) and one patient with leukaemia (3.2%) had minimum residual disease on the extracted ovarian tissue. Of the 14 patients (>12 years) who completed treatment, 12 (85.7%) had primary ovarian insufficiency (POI) more than a year after treatment. Two out of 31 (6.5%) died because of recurrence of their underlying disease (median 28 months, range 0-60 months). Oocyte cryopreservation, as an additional and salvage fertility preservation treatment, was suggested to five patients with biochemical status POI (procedures pending). CONCLUSION: The primary disease and patients' ages varied in fertility preservation for children and adolescents. Our patient selection criteria might be appropriate over a short follow-up period.

Learning Curve of Surgeons Performing Laparoscopic Ovarian Tissue Transplantation in Women with Premature Ovarian Insufficiency: A Statistical Process Control Analysis.

STUDY OBJECTIVE: To analyze patient safety in laparoscopic ovarian tissue transplantation surgery by tracking the rate of postoperative complications and the learning curves of the surgeons by statistical process control analysis. DESIGN: A retrospective study. SETTING: A university-affiliated hospital. PATIENTS: A total of 100 patients with premature ovarian insufficiency who underwent ovarian tissue cryopreservation by vitrification and then autologous transplantation of frozen-thawed ovarian tissues with in vitro activation. INTERVENTIONS: Ovarian tissue cryopreservation, in vitro activation, and transplantation. MEASUREMENTS AND MAIN RESULTS: We assessed the surgery complications, differences in total surgery time, transplantation time, and transplantation time per ovarian sheet in operations performed by 3 experienced laparoscopic surgeons. Surgeon A performed 80 operations; surgeon B, 29 operations; and surgeon C, 20 operations. Complications occurred in 1.55% of the procedures. Although all 3 surgeons' performance never fell below the unacceptable failure limit, only surgeon A became competent after 66 cases. CONCLUSION: The laparoscopic ovarian tissue transplantation surgery was generally safe given that the postoperative complications were infrequent (1.55%). Although the performance of all 3 surgeons was acceptable, only surgeon A attained the level of competency after 66 cases. The transplantation method may not be the key factor for reducing surgery time in this surgery. An efficient ovarian tissue transplantation team is more important in reducing the surgery time than the surgeon's surgical technique alone.

Quantification of residual cryoprotectants and cytotoxicity in thawed bovine ovarian tissues after slow freezing or vitrification.

STUDY QUESTION: How much residual cryoprotectant remains in thawed/warmed ovarian tissues after slow freezing or vitrification? SUMMARY ANSWER: After thawing/warming, at least 60 min of diffusion washing in media was necessary to significantly reduce the residual cryoprotectants in ovarian tissues frozen by slow freezing or vitrification. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) by slow freezing has been the conventional method; while the vitrification method has gained popularity for its practicality. The main concern about vitrification is how much potentially toxic residual cryoprotectant remains in the warmed tissues at the time of transplantation. STUDY DESIGN, SIZE, DURATION: This was an animal study using the ovarian tissues from 20 bovine ovaries. The duration of this study was from 2018 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortex tissues were prepared from 20 bovine ovaries and assigned randomly to groups of fresh (non-frozen) control, slow freezing with 1.5 M dimethyl sulfoxide (DMSO), 1.5 M 1,2-propanediol (PROH) and vitrification with 35% ethylene glycol (EG). The residual cryoprotectant concentrations in thawed/warmed tissues were measured by gas chromatography at the following time points: frozen (before thawing/warming), 0 min (immediately after thawing/warming), 30, 60 and 120 min after diffusion washing in media. Next, the ultrastructural changes of primordial follicles, granulosa cells, organelles and stromal cells in the ovarian tissues (1 mm × 1 mm × 1 mm) were examined in fresh (non-frozen) control, slow freezing with DMSO or PROH and vitrification with EG groups. Real-time quantitative PCR was carried out to examine the expressions of poly (ADP-ribose) polymerase-1 (PARP1), a DNA damage sensor and caspase-3 (CASP3), an apoptosis precursor, in thawed/warmed ovarian tissues that were washed for either 0 or 120 min and subsequently in tissues that were ex vivo cultured for 24 or 48 h. The same set of tissues were also used to analyze the protein expressions of gamma H2A histone family member X (γH2AX) for DNA double-strand breaks and activated caspase-3 (AC3) for apoptosis by immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: The residual cryoprotectant concentrations decreased with the extension of diffusion washing time. After 60 min washing, the differences of residual cryoprotectant between DMSO, PROH and EG were negligible (P > 0.05). This washing did not affect the tissue integrity or significantly elevate the percentage of AC3 and γH2AX positive cells, indicating that tissues are safe and of good quality for transplantation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Since the study was performed with ovarian tissues from bovines, generalizability to humans may be limited. Potential changes in ovarian tissue beyond 120 min were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: This study addresses concerns about the cytotoxicity of EG in warmed ovarian tissues and could provide insights when devising a standard vitrification protocol for OTC. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science to N.S.

Ovarian transplantation with robotic surgery and a neovascularizing human extracellular matrix scaffold: a case series in comparison to meta-analytic data.

OBJECTIVE: To report our experience with robot-assisted (RA) autologous cryopreserved ovarian tissue transplantation (ACOTT) with the use of a neovascularizing extracellular matrix scaffold. DESIGN: Case series with meta-analytic update. SETTING: Academic. PATIENT(S): Seven recipients of RA-ACOTT. INTERVENTION(S): Before or shortly after initiating chemotherapy, ovarian tissue was cryopreserved from 7 women, who then underwent RA-ACOTT 9.9 ± 1.8 years (range, 7-12 years) later. Perioperatively, they received transdermal estrogen and low-dose aspirin to enhance graft vascularization. Ovarian cortical pieces were thawed and sutured on an extracellular matrix scaffold, which was then robotically anastomosed to the bivalved remaining ovary in 6 cases and retroperitoneally (heterotopic) to the lower abdomen in 1 case. MAIN OUTCOME MEASURE(S): Ovarian function return, the number of oocytes/embryos, aneuploidy %, live births, and neonatal outcomes were recorded. Graft longevity was compared with the mean from the meta-analytic data. RESULT(S): Ovarian function returned 13.9 ± 2.7 weeks (11-16.2 weeks) after ACOTT, and oocytes were retrieved in all cases with 12.3 ± 6.9 embryos generated. In contrast to orthotopic, the heterotopic ACOTT demonstrated low embryo quality and an 80% aneuploidy rate. A recipient did not attempt to conceive and 2 needed a surrogate, whereas 4 of 4 delivered 6 healthy children, compared with 115 of 460 (25% pregnancy rate) from the meta-analytic data (n = 79). The mean graft longevity (43.2 ± 23.6/47.4 ± 22.8 months with/without sensitivity analysis) trended longer than the meta-analytic mean (29.4 ± 22.7), even after matching age at cryopreservation. CONCLUSION(S): In this series, RA-ACOTT resulted in extended graft longevity, with ovarian functions restored in all cases, even when the tissues were cryopreserved after chemotherapy exposure.

Survey of understanding and awareness of fertility preservation in pediatric patients: Is conversation about fertility preservation unpleasant for pediatric patients?

Objective: To verify understanding and awareness of fertility preservation (FP) in pediatric patients undergoing FP treatments. Methods: A questionnaire survey was conducted before and after explanation of fertility issues and FP treatments for patients 6-17 years old who visited or were hospitalized for the purpose of ovarian tissue cryopreservation (OTC) or oocyte cryopreservation (OC), or sperm cryopreservation between October 2018 and April 2022. This study was approved by the institutional review board at St. Marianna University School of Medicine (No. 4123, UMIN000046125). Result: Participants in the study comprised 36 children (34 girls, 2 boys). Overall mean age was 13.3 ± 3.0 years. The underlying diseases were diverse, with leukemia in 14 patients (38.9%), brain tumor in 4 patients (11.1%). The questionnaire survey before the explanation showed that 19 patients (52.8%) wanted to have children in the future, but 15 (41.7%) were unsure of future wishes to raise children. And most children expressed some degree of understanding of the treatment being planned for the underlying disease (34, 94.4%). Similarly, most children understood that the treatment would affect their fertility (33, 91.7%). When asked if they would like to hear a story about how to become a mother or father after FP which including information of FP, half answered "Don't mind" (18, 50.0%). After being provided with information about FP treatment, all participants answered that they understood the adverse effects on fertility of treatments for the underlying disease. Regarding FP treatment, 32 children (88.9%) expressed understanding for FP and 26 (72.2%) wished to receive FP. "Fear" and "Pain" and "Costs" were frequently cited as concerns about FP. Following explanations, 33 children (91.7%) answered "Happy I heard the story" and no children answered, "Wish I hadn't heard the story". Finally, 28 of the 34 girls (82.4%) underwent OTC and one girl underwent OC. Discussion: The fact that all patients responded positively to the explanations of FP treatment is very informative. This is considered largely attributable to the patients themselves being involved in the decision-making process for FP. Conclusions: Explanations of FP for children appear valid if age-appropriate explanations are provided.

Case Report: Young Adults With Breast Cancer: A Case Series of Fertility Preservation Management and Literature Review.

Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, with 50% adolescent and YAs being diagnosed and 15-44-year-old women showing excellent 5-year survival. Surgical-chemoradiation therapy often results in excellent survivorship with an increased incidence of treatment-induced subfertility. Therefore, adding fertility preservation (FP) to the primary cancer treatment is necessary. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly. To date, the selection of oocytes, embryos and ovarian tissue is widely available as an FP treatment. PGT could reduce the risk of BRCA mutation transmission amongst BRCA carriers before pregnancy planning. Otherwise, gonadotropin-releasing hormone analog has no gonadoprotective effect and thus should not be considered as an FP option.

Comparison of open and a novel closed vitrification system with slow freezing for human ovarian tissue cryopreservation.

PURPOSE: To investigate the differences concerning post-thawing/warming follicle survival, DNA damage and apoptosis in human ovarian tissues cryopreserved by slow freezing, open, or closed vitrification methods. METHODS: A total of 50 pieces of 5 × 5 × 1 mm ovarian cortical pieces were harvested (5 donor ovaries; mean age 31 ± 6.62 years). From each donor, one cortical piece was used as baseline; the remaining were randomly assigned to slow freezing (SF), vitrification using open device (VF-open), or closed device (VF-closed) groups. After 8-10 weeks of cryostorage, tissues were evaluated 4 h after thawing/warming. Histological analysis was evaluated for follicle survival (primordial and primary follicle densities) by H&E staining. The percentages of primordial and primary follicles with DNA double-strand breaks (γH2AX) and apoptotic cell death pathway activation (AC3) were immunohistochemically assessed. Data were analysed using one-way ANOVA and LSD post hoc comparison. RESULTS: Compared to the baseline, primordial follicle (pdf) densities significantly declined in all cryopreserved groups (SF, VF-open, and VF-closed, P < 0.05). However, the total and non-apoptotic pdf densities were similar among SF, VF-open, and VF-closed. SF and VF with either open or closed devices did not increase the percentages of primordial or primary follicles with DNA double-strand breaks (DSBs) or apoptosis compared to the baseline or among the freezing methods in the present study. CONCLUSION: Based on the intact primordial follicle survival, DNA damage, and apoptosis rates after thawing/warming, SF vs VF with either open or newly developed closed devices appear to be comparable.

Surgical management of unilateral oophorectomy for ovarian tissue cryopreservation in high-risk children and adolescents with varied backgrounds.

PURPOSE: Fertility preservation (FP) for children is still challenging due to an information gap. In particular, there is little information about the surgical aspects of ovarian tissue cryopreservation (OTC) for children. In the present study, the appropriateness of preoperative management and the criteria of our cases were investigated with the aim of establishing a safe OTC procedure. METHODS: A total of 25 girls who underwent OTC from November 2015 through May 2020 were retrospectively analyzed with IRB approval. RESULTS: The median age of the patients was 13 (1-17) years. The medical indications were varied (e.g., leukemia, lymphoma, brain tumor), and included rare diseases. Seventeen cases (68%) underwent OTC during chemotherapy or radiotherapy, and 21 (84%) had comorbidities. All cases underwent ovarian tissue retrieval (OTR) with laparoscopy, and the median operating time was 64 (36-97) min, with little bleeding. Although two had complications, all patients started treatment on schedule. The median WBC and CRP increases a day after OTR were 0 (- 4400 to + 5200)/µl and 0.21 (- 0.2 to 0.87) mg/dl, respectively, with no complications. CONCLUSION: As long as the preoperative criteria are met, OTC could be possible even for children with a severe blood condition. In such cases, the degrees of the WBC and CRP elevations are useful to assess surgical infection.

[Promotion of Equal Access to Medical Services for Children, Adolescent and Young Adult(CAYA)Cancer Patients with Reproductive Problems-A Nationwide Expansion of the Regional Oncofertility Network in Japan].

OBJECTIVES: Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan. METHODS: Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion. RESULTS: Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12). DISCUSSION: CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.