Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

PURPOSE: To clarify the reproductive outcomes of fertility preservation (FP) treatment. METHODS: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. RESULTS: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. CONCLUSION: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

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).

An adolescent and young adult (AYA) cancer education initiative aimed at healthcare students in Japan.

BACKGROUND: The focus on cancer in adolescents and young adults (AYA) has increased in recent years. We participated in an event called AYA week 2021 as part of a research project of the Ministry of Health, Labour and Welfare (MHLW) and conducted a fact-finding survey to collect information for raising public awareness of AYA-generation cancers and to improve support for AYA-generation cancer patients. METHODS: A 25-item questionnaire survey was conducted through requests sent to the deans of medical schools and presidents of related universities across Japan and by advertising on social networking sites and friendship networks. Furthermore, the effects of a lecture given by three cancer survivors on their cancer experience were examined. RESULTS: A total of 1288 healthcare students participated. The most common age group was between 20 and 24 years, with the majority being medical students (83%). The AYA cancer-educated population had more knowledge about AYA-generation cancers than the overall group. At present, very few people are familiar with AYA-generation cancers (30.5%), which highlights the importance of school education. There were 163 participants who attended the lecture given by the cancer survivors, of whom 108 completed the questionnaire. The results showed high participant satisfaction related to the lecture given by cancer survivors, suggesting that such lectures could help educate and raise awareness about AYA-generation cancers. CONCLUSIONS: The knowledge survey and lecture given by cancer survivors had educational effects. Many healthcare students responded positively, suggesting the efficacy of these types of initiatives.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

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.

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.

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.

Guidance on the need for contraception related to use of pharmaceuticals: the Japan Agency for Medical Research and Development Study Group for providing information on the proper use of pharmaceuticals in patients with reproductive potential.

BACKGROUND: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published guidelines on the use of cancer treatments in young people of reproductive potential. However, no such guideline is available in Japan. Therefore, this project aimed to gather relevant data and draft a respective guidance paper. METHODS: From April 2019 to March 2021, the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential at the Japan Agency for Medical Research and Development gathered opinions from experts in reproductive medicine, toxicology, and drug safety measures. The group considered these opinions, the FDA and EMA guidelines, and relevant Japanese guidelines and prepared a guidance paper, which they sent to 19 related organizations for comment. RESULTS: By November 2020, the draft guidance paper was completed and sent to the related organizations, 17 of which provided a total of 156 comments. The study group finalized the guidance paper in March 2021. CONCLUSIONS: The "Guidance on the Need for Contraception Related to Use of Pharmaceuticals" (The report of the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Japan Agency for Medical Research and Development: JP20mk0101139) is expected to help Japanese healthcare professionals provide fertility-related care and advice to adolescents, and young adults with cancer and their families.

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.

A practical survey of fertility-preservation treatments in the startup phase in Japan.

AIM: The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions. METHODS: This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016. RESULTS: Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40-41 years old and the use of eggs to patients 44-45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified. CONCLUSIONS: Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities.

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.

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.

The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation.

BACKGROUND: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. MATERIALS AND METHOD: A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. RESULTS: The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. CONCLUSION: FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. IMPLICATIONS FOR PRACTICE: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.

Recognition and attitudes of Japanese hematologists on sperm banking before chemotherapy: present status from nationwide questionnaire survey.

BACKGROUND: Treatment advancements have improved young cancer patients' survival rate considerably. Fertility preservation has become a very important tool in the prevention of treatment-induced gonadal toxicity. This study aimed to examine hematologists' awareness of its necessity and importance. METHODS: Questionnaires were mailed to the directors of 230 institutes that treated hematological malignancies in adults. The directors were asked to provide information regarding their institutes, collaboration with sperm banks, the number of patients treated per year, selection criteria for patients providing information, and their awareness of and attitudes toward sperm preservation. RESULTS: The response rate was 40.0%. Municipal and private hospitals treated patients significantly less frequently relative to university hospitals (p = .002). Of the 92 participating hematology institutions, 17 included sperm banks and 69 collaborated with sperm banks in neighboring institutions. Many participants stated that sperm preservation should be performed before chemotherapy; however, only 38% provided sperm preservation information to all patients. Participants in facilities without sperm banks exhibited significantly lower levels of knowledge regarding sperm preservation, relative to those from institutions with sperm banks, and found discussing fertility preservation burdensome. This trend was identical to that observed in a survey conducted 10 years earlier. CONCLUSION: Many hematologists did not appear to possess sufficient knowledge regarding fertility preservation. Moreover, few institutions included sperm banks, and a considerable burden was exerted on hematologists. The introduction of support systems is required to promote sperm preservation before cancer treatment.

Current state and future possibilities of ovarian tissue transplantation.

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.

Aromatase inhibitor use during ovarian stimulation suppresses growth of uterine endometrial cancer in xenograft mouse model.

STUDY QUESTION: Could aromatase inhibitors (AI) be used to reduce risks of uterine endometrial cancer growth or recurrence during ovarian stimulation? SUMMARY ANSWER: In a xenograft mouse model of endometrial cancer, concomitant AI administration suppressed the growth of endometrial cancer during ovarian stimulation. WHAT IS KNOWN ALREADY: Recurrence and mortality rates of estrogen receptor-positive early breast cancer are reduced by long-term AI administration. Concomitant AI use for ovarian stimulation in patients with breast cancer is recommended for reducing estrogen-related potential risks. However, the efficacy of concomitant AI use for estrogen receptor-positive endometrial cancer have not been demonstrated conclusively by clinical or experimental animal studies. STUDY DESIGN, SIZE, DURATION: Forty nude mice xenografted with uterine endometrial cancer cells were allocated to four groups. Group 1: no ovarian stimulation (control). Group 2: ovarian stimulation. Group 3: AI administration + ovarian stimulation. Group 4: ovariectomy and ovarian stimulation. Tumor growth was evaluated during the 6-week treatment period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ishikawa 3-H-12 uterine endometrial cancer cells (estrogen and progesterone receptors-positive) were transplanted into 6-week-old BALB/cSlc-nu/nu nude mice, followed by interventions 2 weeks later. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to ovarian stimulation alone (Group 2), significant suppressions of tumor growth were observed in other three groups (Groups 1, 3 and 4, all at P < 0.05) and correlated with estrogen levels. AI administration had no apparent impact on embryo development. LIMITATIONS, REASONS FOR CAUTION: In this study, we examined the growth of endometrial cancer tumors using one endometrial cancer cell line. Clinical endometrial cancer or hyperplasia cells can have diverse origins and AI may not be effective against other cancer cell types. WIDER IMPLICATIONS OF THE FINDINGS: Concomitant AI use may provide a chance for safer childbirth by for patients with endometrial cancer or hyperplasia. STUDY FUNDING/CONPETING INTEREST(S): This study was supported by the Graduate Student Aid from the St. Marianna University School of Medicine. The authors declare no competing interests.

Preliminary human application of optical coherence tomography for quantification and localization of primordial follicles aimed at effective ovarian tissue transplantation.

PURPOSE: The purpose of this study was to evaluate the possible clinical application of optical coherence tomography for assessing ovarian reserve in individual specimens of human ovarian tissue for fertility preservation. METHODS: Ovarian tissue examination by optical coherence tomography was performed before ovarian tissue cryopreservation. Three of the four subjects had hematological disease or cancer, and they faced a threat to their fertility due to impending chemotherapy. One patient underwent ovarian tissue extraction for in vitro activation of dormant follicles as fertility treatment. RESULTS: The current full-field optical coherence tomography technique can detect primordial follicles in non-fixed and non-embedded human ovarian tissue. These images are well correlated with histological evaluation and the ovarian reserve test, including follicle counts. CONCLUSION: It was demonstrated that optical coherence tomography could assess localization of primordial follicles and ovarian reserve in specimens of non-fixed human ovarian cortex, although optimization for examination of human ovarian tissue is needed for clinical application. Additionally, this technique holds the possibility of assessing the ovarian reserve of patients with unevaluable ovarian reserve. TRIAL REGISTRATION NUMBER: UMIN000023141.