Differences Between Cancer Survivors and Healthy Subjects in Factors that Facilitate and Obstruct the Use of the Foster Parent System and Special Adoption System: A Nationwide Cross-Sectional Study in Japan.

Purpose: To investigate factors that obstruct and facilitate the use of the foster parent and special adoption systems (i.e., foster systems) by cancer survivors, and examine how to effectively provide information. Methods: This was a cross-sectional study that compared the results of a questionnaire survey of foster parents and adoptive parents (i.e., foster parents) who were and were not cancer survivors belonging to foster parent associations in 33 locations in Japan. This study was supported by a 2022 Ministry of Health, Labor, and Welfare Grant-in-Aid for Scientific Research (Grant No. 20EA1004). Results: "Lack of information," an obstructive factor and "Sympathetic understanding and cooperation from my partner and family," a facilitative factor were the highest score in both groups. Significant differences between the two groups were found in "Support from government agencies and others for foster parents," a facilitative factor, which was lower in the cancer survivors' group. There were no other significant differences between both the groups. Conclusion: This study found that when considering the use of the foster systems, a lack of information was the biggest obstructive factor and family understanding was the most helpful for both cancer survivors and noncancer groups. It was thought that stronger government support for cancer survivors might encourage cancer survivors to consider becoming foster parents. It would be effective for cancer treatment facilities, reproductive medical facilities, the government, and foster parent associations to work together to provide information carefully to cancer 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.

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.

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.

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.

The Scenario of Adoption and Foster Care in Relation to the Reproductive Medicine Practice in Asia.

In vitro fertilization (IVF) is a hallmark of reproductive medicine. However, the inconclusive outcome leads to marital disharmonies; thus, the choices of gamete donation and surrogacy (GD/S) are often offered. In restricted countries, the child-rearing choice through foster/adoption care is promising, but the uptake remains low. We explore the current reproductive services and adoption scenarios in Asian countries to delineate this issue. The web and literature search using PubMed and Ichushi was conducted in Japanese and English using the keywords "adoption", "foster care", "reproductive medicine", including the interview with the respective Asian clinicians. We found that an established adoption system was seen in China, Malaysia, and the Philippines, mainly due to the restriction of GD/S. Although GD/S were allowed in Thailand, Singapore, and India, the different local affordability of IVF cost led to various adoption system scenarios. Nevertheless, the country's economic aspect does influence the establishment of adoption care, mainly due to financial support from local government. Otherwise, the significant barrier was the cultural/religious background leading to low adoption rates. We concluded that the adoption option should always be highlighted as an alternative strategy as it synergistically contributes to children's and infertile couples' welfare.

Poly (ADP-ribose) polymerase inhibitor exposure reduces ovarian reserve followed by dysfunction in granulosa cells.

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.

Oncofertility Treatment Among Breast Cancer Women: A Paradigm Shift of Practice After a Decade of Service.

Purpose: Our center is known as a pioneer center initiating oncofertility service since 2010 in Japan. We demonstrate our transition of this service in regional university hospitals ingenuously. Methods: We compared two phases of service: initial phase (2011 and 2012) and current phase (2019). The comparison included the number of women attending the oncofertility unit, diversity of breast cancer cases, the acceptability of preservation service, and the type of fertility preservation (FP) option offered in between these phases. Results: A total of 58 women were seen during the initial phase as compared with 41 women in the later phase. The mean age at diagnosis was not significantly different between the two periods. The majority of them were married and diagnosed with stage II luminar type. The current phase had a tendency to have a higher anti-Müllerian hormone level although not reaching significance. At least 50% of them declined FP and 84.5% never received ovarian control stimulation in the initial phase. Otherwise, 61% used aromatase inhibitor in the current phase. Only 15.5% in the initial phase received control ovarian stimulation whereas 63.4% in the current phase received it. The ovarian tissue cryopreservation was highly chosen during the initial phase (25.9%), whereas embryo cryopreservation (39%) was highly opted for during the current phase. All of our parameters are comparable between these two phases (p > 0.05). Conclusion: The significant changes of oncofertility practice were observed mainly due to the understanding of the oncofertility concept among reproductive physicians and the acceptance environment, including standard guidelines, supportive society, as well as advancements in cryobiology technique.

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

Purpose: The 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 Methods: We 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. Results: Our 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. Conclusion: Our 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.

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

PURPOSE: The 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 METHODS: We 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. RESULTS: Our 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. CONCLUSION: Our 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.

The Utility of Decision Trees in Oncofertility Care in Japan.

PURPOSE: To identify the utility and issues associated with the use of decision trees in oncofertility patient care in Japan. METHODS: A total of 35 women who had been diagnosed with cancer, but had not begun anticancer treatment, were enrolled. We applied the oncofertility decision tree for women published by Gardino et al. to counsel a consecutive series of women on fertility preservation (FP) options following cancer diagnosis. Percentage of women who decided to undergo oocyte retrieval for embryo cryopreservation and the expected live-birth rate for these patients were calculated using the following equation: expected live-birth rate = pregnancy rate at each age per embryo transfer × (1 - miscarriage rate) × No. of cryopreserved embryos. RESULTS: Oocyte retrieval was performed for 17 patients (48.6%; mean ± standard deviation [SD] age, 36.35 ± 3.82 years). The mean ± SD number of cryopreserved embryos was 5.29 ± 4.63. The expected live-birth rate was 0.66. CONCLUSIONS: The expected live-birth rate with FP indicated that one in three oncofertility patients would not expect to have a live birth following oocyte retrieval and embryo cryopreservation. While the decision trees were useful as decision-making tools for women contemplating FP, in the context of the current restrictions on oocyte donation and the extremely small number of adoptions in Japan, the remaining options for fertility after cancer are limited. In order for cancer survivors to feel secure in their decisions, the decision tree may need to be adapted simultaneously with improvements to the social environment, such as greater support for adoption.