New Insights on In Vitro Maturation of Oocytes for Fertility Preservation.

In the last decade, the evolution of oncofertility has sparked a resurgence of interest in in vitro maturation (IVM) due to its suitability in certain oncological scenarios where controlled ovarian hyperstimulation may not be feasible. The retrieval of immature cumulus-oocyte complexes from small antral follicles, regardless of the menstrual cycle phase, presents a swift opportunity to vitrify mature oocytes or embryos post-IVM in urgent situations or when stimulation is not advisable. Harvesting immature cumulus-oocyte complexes and immature oocytes can be achieved transvaginally or directly in the laboratory from extracorporeal ovarian tissue. Although IVM has transitioned from an experimental status due to safety validations, it relies on the intricate process of oocyte maturation. Despite successful live births resulting from IVM in fertility preservation contexts, the comparatively lower developmental competence of in vitro matured oocytes highlights the necessity to enhance IVM culture systems. Recent advancements in IVM systems hold promise in bolstering oocyte competence post-IVM, thereby narrowing the gap between IVM and outcomes from ovarian stimulation. Additionally, for optimizing the chances of conception in cancer survivors, the combination of IVM and ovarian tissue cryopreservation stands as the favored choice when ovarian stimulation is unfeasible.

[Fertility preservation in patients with hematopoietic diseases].

The prognosis of hematopoietic diseases has been improving over the past several decades, and measures to fulfill patients' wishes to have children are needed to improve survivors' quality of life. In Japan, the Japan Society for Fertility Preservation has taken the lead in developing guidelines, a national registry, and a nationwide uniform subsidy system. When considering fertility preservation in patients with hematopoietic diseases, interdisciplinary collaboration between oncology and onco-fertility is necessary to solve problems specific to hematopoietic diseases, such as the short time window between the onset of disease and the start of treatment, complications associated with fertility preservation treatment such as bleeding or ovarian hyperstimulation syndrome, and contamination of collected tissue with hematopoietic tumor cells. This article outlines the basic concept of fertility preservation in patients with hematopoietic diseases and recently established strategies for women with chronic myelogenous leukemia. It will also share some treatment innovations that can be considered in cases when fertility preservation treatment may be challenging.

[Fertility preservation in women affected by a gynecologic carcinoma]. / Préservation de la ­fertilité chez les patientes présentant un ­cancer ­gynécologique.

Gynecological cancers quite often affect young women who wish to preserve their fertility. In addition, with the advancement in age of first pregnancies, this problem has currently taken on a significant scale. Most often, fertility preservation is possible provided that the cancerous tumor is discovered at an early stage and of a non-aggressive histological nature. For uterine cancers (cervix and endometrium), surgery preserving uterine function (associated with hormone therapy for endometrial cancers) is often possible for early tumor stages. For ovarian cancers, indications for fertility preservation are rare and reserved for certain histological types, mainly borderline tumors.

Les cancers gynécologiques touchent assez souvent des femmes jeunes qui souhaitent préserver leur fertilité. De plus, avec l'avancement en âge des premières grossesses, cette problé­matique a pris actuellement une ampleur non négligeable. Le plus souvent une préservation de la fertilité est possible à la condition que la tumeur cancéreuse soit découverte à un stade précoce et de nature histologique peu agressive. Pour les ­cancers de l'utérus (col et endomètre), une chirurgie préservant la fonction utérine (associée à une hormonothérapie pour les cancers endométriaux) est souvent possible pour les stades ­tumoraux débutants. Pour les cancers ovariens, les indications de préser­vation de la fertilité sont rares et réservées à certains types ­histologiques dont essentiellement les tumeurs ­borderline.

Does surgery to preserve fertility in Sertoli-Leydig cell tumours increase the likelihood of spontaneous conception?

A nulligravida in her 30s presented with primary infertility and secondary amenorrhoea. General examination revealed virilisation; sonological examination detected a right ovarian solid mass. International Ovarian Tumour Analysis (IOTA) was suggestive of malignancy and serum testosterone was raised. A strong clinical suspicion and negative tumour markers pointed towards androgen producing sex cord stromal ovarian neoplasm. MRI excluded pelvic lymphadenopathy. Given the patient's desire for conception, fertility sparing staging laparotomy was done. Histopathology confirmed Sertoli-Leydig cell tumour (SLCT) International Federation of Gynaecology and Obstetrics stage IA. Serum testosterone fell drastically by day 10. Spontaneous menstruation resumed within 30 days. The significance of SLCTs as a differential diagnosis in young women with secondary amenorrhoea and virilising features underscores the role of fertility-preserving surgery in certain circumstances. Here we discuss the clinical features, diagnostic challenges and management strategies for SLCTs, emphasising the need for multidisciplinary collaboration and option of fertility preservation in early stages.

[Oncological and reproductive outcomes after fertility-sparing surgery in patients with stage â ¡-â ¢ borderline ovarian tumor].

Objective: To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT). Methods: The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed. Results: (1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ (HR=4.555, 95%CI: 1.525-13.607; P=0.007) and micropapillary subtype (HR=2.396, 95%CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions: Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

Fertility-sparing surgical interventions for low-risk, non-metastatic gestational trophoblastic neoplasia.

BACKGROUND: The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission. OBJECTIVES: To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN. DATA COLLECTION AND ANALYSIS: We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events. MAIN RESULTS: We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported. AUTHORS' CONCLUSIONS: Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population.

Effects of different surgical extents on prognosis of patients with malignant ovarian sex cord-stromal tumors: a retrospective cohort study.

Malignant ovarian sex cord-stromal tumors are rare neoplasms that account for approximately 5-7% of all ovarian malignancies, and they are primarily treated with surgery. The prognosis of patients with different surgical extents remains controversial. Therefore, the effects of different surgical extents on the prognosis of patients were explored in this retrospective cohort study. Patients with malignant ovarian sex cord-stromal tumors who underwent surgical treatment from January 2000 to December 2019 were selected. Disease-free survival and overall survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Prognosis factors were identified by Cox regression analysis. P < 0.05 was considered a statistically significant difference. A total of 278 patients with an average age at onset of 42 (8-78) years old were enrolled. The median follow-up time was 73 months. There was no significant difference in disease-free survival and overall survival rates between patients who underwent fertility-sparing surgery and those who underwent Non-fertility-sparing surgery, and between patients underwent staging surgery and those underwent Non-staging surgery. Age < 40 years (P = 0.024), stage II-III (P = 0.038), a high CA125 level (P = 0.035) and WT-1 (+) (P = 0.016) were independent risk factors for recurrence. In conclusion, different surgical extents have no significant influence on recurrence and survival status of patients with malignant ovarian sex cord-stromal tumors.

Fertility-sparing treatment in MSI-H/MMRd endometrial carcinoma or atypical endometrial hyperplasia: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. METHODS: The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. RESULTS: The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. CONCLUSION: EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype.

Fertility-sparing treatment with conization versus radical hysterectomy in patients with early-stage cervical cancer: inverse propensity score weighted analysis.

OBJECTIVE: To report 20 years of experience with fertility-sparing surgery for patients with early-stage cervical cancer, comparing the oncological outcomes with outcomes for those who underwent a radical hysterectomy. METHODS: Patients with pre-operative stage IA1 with lymphovascular space invasion, IA2 and IB1 cervical cancer (any grade) were included (2018 International Federation of Gynecology and Obstetrics staging system). Inclusion criteria comprised age (18-44 years), histology (squamous, adenocarcinoma, or adenosquamous) and absence of previous/concomitant cancer. A thorough counseling about oncological and obstetrical potential risks was mandatory for patients asking for fertility sparing. Results for consecutive patients who underwent fertility-sparing surgery (cervical conization and nodal evaluation) were analyzed and compared with results for patients treated with radical surgery. Oncological outcomes were assessed with a propensity score adjustment with inverse probability of treatment weighting. RESULTS: Overall, 109 patients were included in the study. Ten patients abandoned the fertility-sparing route because of nodal involvement (n=5), margin positive (n=2), or because patients requested radical treatment (n=3). Sentinel node mapping was performed in 19 of 49 (38.8%) patients in the fertility-sparing surgery group. Among the patients in the fertility-sparing group, 6 (12.2%) patients relapsed. 34 (69.4%) patients attempted to conceive. Pre-operative covariates selected to define the probability of having either fertility-sparing or radical surgery were well balanced using inverse probability of treatment weighting. Pathological features were similar between the groups, including grading, histotype, stage, and lymphovascular space invasion. After a median follow-up of 38.8 (range 5-186) months there were no differences in progression-free survival (p=0.32) and overall survival (p=0.74) between the fertility-sparing and radical hysterectomy groups. The results after inverse probability of treatment weighting adjustment did not show significant differences in progression-free survival (p=0.72) and overall survival (p=0.71) between the groups. CONCLUSION: Fertility-sparing surgery based on conization plus laparoscopic lymph node evaluation, may be considered safe and effective for patients with early-stage cervical cancer.

Desire for pregnancy and fertility preservation in young patients with breast cancer.

BACKGROUND: Data on the desire for pregnancy and the status of fertility preservation (FP) in patients with breast cancer remain unclear. This study aimed to determine the status of patients with breast cancer who desired pregnancy and FP implementation before systemic therapy. METHODS: This retrospective study surveyed the institutional clinical databases and electronic medical records of patients aged < 43 years with stages 0-III primary breast cancer during surgery and treated between April 2020 and March 2021. All patients were enquired about their desire for pregnancy in a questionnaire by "present," "absent," and "unsure" at their first visit. The correlation between the desire for pregnancy, implementation of FP, and clinicopathological factors was investigated. RESULTS: Among 1005 patients who underwent surgery for primary breast cancer, 146 were included in the analysis. Of them, 34 (23.3%) patients had a desire for pregnancy, and 45 (30.8%) chose "unsure." Factors associated with the desire for pregnancy were younger age during surgery (p < 0.0022), unmarried status (p < 0.001), nulliparity (p < 0.001), early-stage disease (p = 0.0016), and estrogen receptor positivity (p = 0.008). Among 115 patients who underwent systemic therapy, 13 (11.3%) underwent FP before systemic therapy. Patients who were nulliparous frequently pursued FP (p = 0.0195). The proportion of FP implementation was low in patients who received neoadjuvant chemotherapy (p = 0.0863). CONCLUSIONS: Our study suggests that unmarried, nulliparous, and younger patients were more interested in pregnancy, and nulliparous patients frequently pursued FP.

Innovations in 3D ovarian and follicle engineering for fertility preservation and restoration.

In-vitro maturation (IVM) is the process of cultivating early-stage follicles from the primordial to the antral stage and facilitating the maturation of oocytes outside the body within a supportive environment. This intricate procedure requires the careful coordination of various factors to replicate the natural ovarian conditions. Advanced techniques for IVM are designed to mimic the natural ovarian environment and enhance the development of follicles. Three-dimensional (3D) culture systems provide a more biologically relevant setting for follicle growth compared to traditional two-dimensional (2D) cultures. Traditional culture systems, often fail to support the complex process of follicle development effectively. However, modern engineered reproductive tissues and culture systems are making it possible to create increasingly physiological in-vitro models of folliculogenesis. These innovative methods are enabling researchers and clinicians to better replicate the dynamic and supportive environment of the ovary, thereby improving the outcomes of IVM offering new hope for fertility preservation and treatment. This paper focuses on the routine 3D culture, and innovative 3D culture of ovary and follicles, including a tissue engineering scaffolds, microfluidic (dynamic) culture system, organ-on-chip models, EVATAR system, from a clinical perspective to determine the most effective approach for achieving in-vitro maturation of follicles. These techniques provide critical support for ovarian function in various ovarian-associated disorders, including primary ovarian insufficiency (POI), premature ovarian failure (POF), ovarian cancer, and age-related infertility.

Ovarian tissue cryopreservation after graft failure of allogeneic hematopoietic stem cell transplantation: first report and literature review.

Background: Hematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT. Case presentation: A 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted. Conclusion: OTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol.

BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Fertility outcomes in stage I ovarian immature teratomas.

OBJECTIVE: To evaluate the impact of adjuvant chemotherapy, type of ovarian surgery, and the surgical approach on fertility in patients with stage I immature teratoma of the ovary. METHODS: Clinicopathologic data were retrospectively collected and analyzed from a cohort of 47 patients with childbearing desire treated for a stage I immature teratoma of the ovary at IRCCS San Gerardo dei Tintori Hospital, Monza, Italy. Multivariate logistic regression was used to address the influence of chemotherapy and type of surgery on the outcome. RESULTS: Among the patients included, 78.7% (37/47) were able to get pregnant, with a live birth rate of 80.9% (51/63 pregnancies). These rates were not different between adjuvant chemotherapy versus surveillance group (62.5% (5/8) and 82.0% (32/39), respectively; p=0.22) nor between the type of ovarian surgery (cystectomy vs unilateral salpingo-oophorectomy; p=0.57) and surgical approach (laparotomy or laparoscopy; p=0.18). A statistically significant difference was found for stage of disease (a decrease in pregnancy rate from 86.5% (32/37) for stage IA to 50.0% for stage IC (5/10); p=0.02), but it was not confirmed in the multivariate analysis. After relapse diagnosis and management, a total of 62.5% (5/8) of patients conceived and had at least one live birth baby. CONCLUSIONS: The fertility-sparing approach is feasible in this population, and fertility does not depend on surgical approach or post-operative treatment. However, adjuvant chemotherapy should be carefully evaluated in this setting.

Liposome-based Freezing Medium Improves the Outcome of Mouse Prepubertal Testicular Tissue Cryopreservation.

Cryopreservation of testicular tissue holds an important role in the field of fertility preservation, particularly for prepubertal boys diagnosed with cancer. However, prepubertal testicular tissue cryopreservation is still considered to be in the experimental stage necessitating the refinement of cryopreservation protocol. Considering the fact that loss of membrane lipids is the primary cause of freeze-thaw-induced loss of testicular cell functions, in this study, we explored the beneficial properties of exogenous supplementation of membrane lipids in the form of liposomes in enhancing the cryosurvival of prepubertal testicular tissue. The freezing medium supplemented with liposomes (prepared from soy lecithin, phosphatidylethanolamine, phosphatidylserine, and cholesterol) was used for the experiments. Prepubertal testicular tissues from Swiss albino mice were cryopreserved in a liposome-containing freezing medium (LFM) composed of 0.25 mg/mL liposomes, 5% DMSO, and 30% FCS in the DMEM/F12 medium using a slow freezing protocol. The tissues were thawed and assessed for various testicular cell functions. Freezing in LFM mitigated the loss of viability, decreased malondialdehyde level (p < 0.05), and reduced apoptosis (p < 0.05) in the testicular cells compared to the testicular tissue cryopreserved in the control freezing medium (CFM). Further, DMSO (5%) appears to be the ideal penetrating cryoprotectant for prepubertal testicular tissue cryopreservation with liposome-based freezing medium. Similar enhancement in cryosurvival of cells was observed in adult human testicular tissue frozen with LFM. These findings highlight the translational value of liposome-based freezing medium in the cryopreservation of testicular tissue of prepubertal boys undergoing chemotherapy.

Utility and Outcomes of Ovarian Tissue Cryopreservation and Transplantation for Gynecologic Cancers: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the utility, success, and safety of ovarian tissue cryopreservation and autologous cryopreserved ovarian tissue transplantation for fertility preservation in patients with gynecologic cancers. DATA SOURCES: A comprehensive search was performed of the MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane Library databases to identify relevant studies on the utility and outcomes of ovarian tissue cryopreservation and autologous cryopreserved ovarian tissue transplantation for gynecologic cancers from inception until January 23, 2024. METHODS OF STUDY SELECTION: Two reviewers independently performed the study selection, data extraction, and risk-of-bias assessment, and the results were then reviewed together. Twenty-three studies were included in the current systematic review. TABULATION, INTEGRATION, AND RESULTS: The resultant data were meta-analyzed to produce a pooled-effect estimate of the utility of ovarian tissue cryopreservation and autologous transplantation in gynecologic cancers as a proportion of all indications. We found that 7.5% and 9.6% of women undergoing ovarian tissue cryopreservation and autologous transplantation, respectively, had gynecologic cancers. In comparison, hematologic malignancies and breast cancer accounted for approximately 66.0% of all indications for these procedures. The return rate for autologous cryopreserved ovarian tissue transplantation in gynecologic cancers (6.0%) was not statistically different from those for other indications. Among women with gynecologic cancer who underwent ovarian stimulation, 27.3% had at least one child, and the ovarian endocrine function was restored in 78.1% of the women after autologous transplantation. The median graft longevity was 32 months, and no graft-site recurrence was reported after autologous transplantation in women with gynecologic cancer. CONCLUSION: Our results suggest that ovarian tissue cryopreservation and autologous transplantation are feasible options for preserving ovarian function in women with gynecologic cancers, although ovarian tissue cryopreservation is underutilized, and further studies are needed to determine the longer-term outcomes of autologous transplantation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42024498522.

Effect of breast cancer prognostic factors on ovarian reserve and response in fertility preservation.

RESEARCH QUESTION: Do breast cancer prognostic factors influence ovarian reserve and response to ovarian stimulation in the context of fertility preservation? DESIGN: Observational, bicentric retrospective study of 352 women with breast cancer who underwent ovarian stimulation using a random start gonadotrophin releasing hormone antagonist protocol and vitrified oocytes between November 2015 and August 2022. Serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were measured. The number of oocytes recovered, maturation rate and follicular output rate (FORT) were analysed according to patients' characteristics and breast cancer prognostic factors. RESULTS: Median age was 34 years (31.1-37.1). Median AFC and serum AMH level were 17 (12-26) follicles and 2 (1.2-3.4) ng/ml, respectively. After ovarian stimulation, 10.5 (6.0-16.0) oocytes were recovered, with eight (4-13) being mature. Mean oocyte maturation rate was 79% (62-92). Antral follicle count (>12) significantly affected the risk of recovering fewer than eight mature oocytes (P < 0.0001, multivariate analysis). Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) and number of oocytes recovered, were 31% (21-50) and 10.5% (6.0-16.0), respectively. FORT index and ovarian stimulation outcomes were not influenced by breast cancer prognostic factors. CONCLUSION: Breast cancer prognostic factors do not influence ovarian reserve markers or response to ovarian stimulation in fertility preservation. Therefore, tumour grade, triple-negative status, HER2 overexpression and high Ki67 should not alter the fertility-preservation strategy when considering ovarian stimulation for oocyte vitrification.

Is Routine Pathology Evaluation of Tissue Removed for Fertility Preservation Necessary?

BACKGROUND: For all fertility preservation (FP) cases at our institution, a biopsy is performed for routine pathology from all gonadal tissue removed. This is not standard at all centers. We reviewed our experience with biopsy for pathological evaluation of ovarian and testicular specimens in FP cases to determine clinical utility. METHODS: The medical records of individuals who underwent ovarian tissue cryopreservation (OTC) or testicular tissue cryopreservation (TTC) between 2011 and 2023 were retrospectively reviewed under an IRB-approved study at a free-standing tertiary care children's hospital. Patient demographics, diagnosis, operative characteristics, and pathology results were collected. RESULTS: One-hundred and eighty-three patients underwent OTC, and 134 patients underwent TTC. All patients had their gonadal tissue biopsied for routine pathology. Malignancy was identified in the biopsies of 4 OTC patients (2.2%) and 2 TTC patients (1.5%). Two OTC patients (1.1%) and 2 TTC patients (1.5%) did not have germ cells identified in their biopsy. All OTC and TTC patients and families elected to continue storing tissue for FP after discussion of pathology findings. CONCLUSIONS: Pathology results provide another data point to help inform patients and their families when making decisions on ovarian or testicular tissue storage and on how tissue may be utilized in the future to restore fertility and/or hormones. There is a low rate of identifying malignancy in gonadal tissue biopsies taken from FP specimens even in patients with known malignancy. However, when malignancy was identified, it could be unexpected and alter the diagnosis and treatment plan significantly for patients. LEVEL OF EVIDENCE: IV.

Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer.

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.