OBJECTIVE: Do platelet-rich plasma (PRP) products, specifically human platelet lysate (hPL) and umbilical cord plasma, enhance vascularization and follicular survival in human ovarian tissue transplanted to immunodeficient mice?
METHODS: Human ovarian tissue was transplanted to subcutaneous pockets in nude mice, followed by daily injections for 6 days of PRP or saline at the transplantation sites. After a grafting period of 3 and 6 days, vascularization was assessed using CD-31 quantification, and gene expression of angiogenic markers (VEGF/Vegf) together with apoptosis-related genes (BAX/BCL-2), oxidative stress markers (HMOX-1/Hmox-1) and pro-inflammatory markers (Il-1β/Il-6/Tnf-α) was quantitively analysed. Follicle density was analysed in the grafts after 4 weeks. Additionally, a pilot study was conducted exploring the suitability of ultrasound scanning for assessing survival and vascularization in ovarian tissue xenografted to mice.
RESULTS: Although there was a significant increase in the CD-31 area from day 3 to day 6 post-grafting, there were no significant differences between the hPL and control groups. Gene expression analysis revealed significant down-regulation of VEGF from day 3 to day 6 for both the hPL and control groups, and significant up-regulation of BAX/BCL-2 in the hPL group compared with the controls. The follicle density showed no significant differences in the hPL group and UCP groups compared with the controls. Furthermore, ultrasound biomicroscopy provided valuable insights into graft morphology, necrotic areas and blood flow, suggesting its potential as a monitoring tool.
CONCLUSIONS: Despite the angiogenic properties of PRP, this study was unable to demonstrate a significant impact of hPL on vascularization or of hPL and UCP on follicular survival in xenotransplanted human ovarian tissue.

Objective: This paper serves as an up-to-date narrative review of the most effective methods and outcomes of ovarian tissue cryopreservation (OTC) with new data comparing this method to oocyte and embryo cryopreservation as well as its utility in restoration of endocrine function. Background: Data on OTC are becoming more available as more patients are achieving cancer remission and choosing to use their cryopreserved tissue to conceive or restore endocrine function. With OTC only recently becoming a non-experimental method of fertility preservation, it is important to evaluate, compare, and optimize current practices to improve live birth outcomes. Methods: A literature search of meta-analyses, systematic reviews, case series, retrospective studies, and randomized control trials was performed using the PubMed database with multiple search terms. Discussion: Current practices and outcomes of OTC remain heterogeneous, though they are becoming more streamlined with the emerging data on successful live births. Multiple aspects of OTC have been studied to optimize protocols, particularly methods of cryopreserving, in vitro maturation, and transplantation. In vitro follicle maturation is a novel application with emerging data on methods and outcomes. OTC is a versatile method not only for fertility preservation but also for hormone restoration as well. With wider usage of OTC, ethical dilemmas will need to be addressed. Conclusions: OTC can be used as fertility preservation for a variety of patients. Recent studies suggest it may be comparable to embryo cryopreservation, but with growing data on live births, comparative studies should continue to be performed. In vitro follicle maturation (IVFM) is a promising application of ovarian tissue harvesting. Data are lacking on cost-effectiveness, patient satisfaction, and morbidity associated with OTC.

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.
METHODS: IV.

BACKGROUND: Treatment for certain childhood cancers and nonmalignant conditions can lead to future infertility and gonadal failure. The risk of treatment delay must be considered when offering fertility preservation (FP) options. We examined the timeline from FP referral to return to treatment (RTT) in pediatric patients who underwent FP due to iatrogenic risk for infertility.
METHODS: A retrospective review was performed of patients with FP consultation due to an increased risk of iatrogenic infertility at Ann & Robert H. Lurie Children\'s Hospital of Chicago from 2018 to 2022. Data on diagnosis, age, treatment characteristics, and procedure were collected.
RESULTS: A total of 337 patients (n = 149 with ovaries, n = 188 with testes) had an FP consultation. Of patients with ovaries, 106 (71.1%) underwent ovarian tissue cryopreservation (OTC), 10 (6.7%) completed ovarian stimulation/egg retrieval (OSER), and 33 (22.1%) declined FP. Of the patients with testes, 98 (52.1%) underwent testicular tissue cryopreservation (TTC), 48 (25.5%) completed sperm banking (SB), and 42 (22.3%) declined FP. Median time from referral to FP consultation was short (ovaries: 2 days, range: 0-6; testes: 1 day, range: 0-5). OSER had a significantly longer RTT versus OTC and no FP (52.5 vs.19.5 vs. 12 days, p = .01). SB had a significantly quicker RTT compared to TTC or no FP (9.0 vs. 21.0 vs. 13.5 days; p = .008). For patients who underwent OTC/TTC and those who declined FP, there was no significant difference in time from consultation to treatment.
CONCLUSIONS: It is feasible to promptly offer and complete FP with minimal delay to disease-directed treatment.

Purpose: In vitro maturation (IVM) of oocytes obtained from ovarian tissue during ovarian tissue cryopreservation (OTC) is a technique for fertility preservation in patients with cancer obviating the need to postpone chemotherapy initiation. Little is known about IVM outcomes in hematological malignancies, especially post-chemotherapy. The purpose of this study was to evaluate the effect of cytotoxic treatment on the potential to retrieve immature oocytes and mature them in vitro and examine the association between serum inflammatory markers and these results. Methods: In this retrospective study, we evaluated inflammation markers, including B symptoms and IVM outcomes of 78 chemotherapy-naive and exposed patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). Results: The mean number of oocytes found was 7.2 ± 7.2. The average number of oocytes matured by IVM was 2.8 ± 3.5, and a mean IVM rate was 32.1 ± 27.7%. All patients in the ALL and AML groups had previous exposure to chemotherapy before OTC, compared with 50.0% (7/14) and 31.9% (15/47) in the NHL and HL groups, respectively. Among patients with lymphoma, chemotherapy exposure was associated with the reduced number of retrieved oocytes (9.8 ± 7.7 vs. 5.3 ± 5.7 oocytes, p = 0.049) in the HL group but not with the number of mature oocytes or IVM rate. B symptoms were not associated with IVM outcomes. Lymphocyte count (ß = 1.584; p = 0.038) and lactate dehydrogenase (ß = 0.009; p = 0.043) were the only significant parameters associated with the number of matured oocytes in a linear regression model. Conclusion: IVM is a promising assisted reproductive technology, which holds great potential for patients in need of urgent fertility preservation or those who cannot receive hormonal stimulation. Our results demonstrate the feasibility of the technique even in the presence of B symptoms and elevated inflammation markers and in patients with previous exposure to chemotherapy.

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal.

Individuals with a disease or treatment that will increase their risk of premature gonadal insufficiency may opt to undergo fertility preservation. Those who are post-pubertal can often cryopreserve gametes, sperm or eggs, to expand their biological family using assisted reproductive technologies. Ovarian tissue cryopreservation (OTC) and testicular tissue cryopreservation may be an option for individuals who are unable to utilize standard fertility preservation techniques. The development of OTC was critical for many patients, including prepubertal children with ovaries that do not yet produce eggs, adolescents who make few good quality eggs and adult women with ovaries who cannot undergo ovarian stimulation. The only option to restore fertility and hormone production following OTC is through ovarian tissue transplantation (OTT). OTC and OTT have been successful for some patients. While OTC is no longer considered experimental by the American Society of Reproductive Medicine, the process is far from standardized. Significant research needs to be done, especially at the point of OTT, to improve the success and longevity of the ovarian tissue function. This article lists the main steps from surgical procurement of the ovarian tissue to transplantation and restoration of function. Our pediatric hospital program has had to decide which options in procurement, processing, cryopreservation and warming will be used in our clinical lab. The options and limitations within the research and analyses are briefly discussed. Literature focusing on techniques to improve OTT effectiveness and longevity was reviewed. OTT studies that performed xenograft experiments after pretreatment of the tissue graft by a ligand or drug, treatment of host, or encapsulation of the ovarian tissue were identified. The intended effects of the treatments include increasing vascularization, reducing apoptosis and directing activation or suppression of primordial follicles. Robust research in this area must continue with rigorous analyses to make strides for improving fertility preservation and restoration options for patients.

UNASSIGNED: To review the program and patient metrics for ovarian tissue cryopreservation (OTC) within a comprehensive pediatric fertility preservation program in its first 12 years of development.
UNASSIGNED: Retrospective review.
UNASSIGNED: A tertiary children\'s hospital in a large urban center between March 2011 and February 2023.
UNASSIGNED: Pediatric patients who underwent OTC.
UNASSIGNED: Unilateral oophorectomy for OTC.
UNASSIGNED: Patient demographics and clinical course information were collected for analysis.
UNASSIGNED: A total of 184 patients underwent OTC in the first 12 years. One hundred fifteen patients were prepubertal at the time of OTC, and 69 were postpubertal. In total, 128 patients (69.6%) received part of their planned therapy before OTC. Starting in 2018, 104 participants (92.0%) donated tissue to research, 99 participants (87.6%) donated blood, and 102 (90.2%) donated media to research. There was a decrease in the median age of patients who underwent OTC from 16.4-6.6 years and an overall increase in the proportion of patients per year that were prepubertal. Forty-eight (26.0%) patients who underwent OTC were outside referrals and traveled from as far as Seattle, Washington.
UNASSIGNED: During the first 12 years of this program, oncofertility research increased, annual tissue cryopreservation cases increased, and the median age of those who underwent OTC decreased. The program was adapted to build a stand-alone gonadal tissue processing suite and specialized in prepubertal ovarian tissue processing. The program will continue to adapt to patient needs in the upcoming decades because restoration technologies advance through research supported by this and collaborating programs.

UNASSIGNED: Anticancer treatments have significantly contributed to increasing cure rates of breast cancer in the last years; however, they can also lead to short- and long-term side effects, including gonadotoxicity, and compromised fertility in young women. Oncofertility is a crucial issue for young patients who have not yet completed their family planning at the time of cancer diagnosis.
UNASSIGNED: This review aims to cover all the latest available evidence in the field of oncofertility, including the gonadotoxicity of currently adopted anticancer therapies in the curative breast cancer setting, the available strategies for fertility preservation and the feasibility of achieving a pregnancy following anticancer treatment completion.
UNASSIGNED: Over the past years, a significant progress has been made in oncofertility care for young women with breast cancer. In the context of the currently available evidence, every young woman with newly diagnosed breast cancer should receive a proper and complete oncofertility counseling before starting any anticancer treatment to increase her chances of future pregnancies.

UNASSIGNED: Infertility is an important late effect of childhood cancer treatment. Ovarian tissue cryopreservation (OTC) is established as a safe procedure to preserve gonadal tissue in (pre)pubertal girls with cancer at high risk for infertility. However, it is unclear whether elective laparoscopic OTC can also be performed safely in infants <1 year with cancer. This systematic review aims to evaluate the reported risks in infants undergoing elective laparoscopy regarding mortality, and/or critical events (including resuscitation, circulatory, respiratory, neurotoxic, other) during and shortly after surgery.
UNASSIGNED: This systematic review followed the Preferred reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guideline. A systematic literature search in the databases Pubmed and EMbase was performed and updated on February 15th, 2023. Search terms included \'infants\', \'intubation\', \'laparoscopy\', \'mortality\', \'critical events\', \'comorbidities\' and their synonyms. Papers published in English since 2000 and describing at least 50 patients under the age of 1 year undergoing laparoscopic surgery were included. Articles were excluded when the majority of patients had congenital abnormalities. Quality of the studies was assessed using the QUIPS risk of bias tool.
UNASSIGNED: The Pubmed and Embase databases yielded a total of 12,401 unique articles, which after screening on title and abstract resulted in 471 articles to be selected for full text screening. Ten articles met the inclusion criteria for this systematic review, which included 1778 infants <1 years undergoing elective laparoscopic surgery. Mortality occurred once (death not surgery-related), resuscitation in none and critical events in 53/1778 of the procedures.
UNASSIGNED: The results from this review illustrate that morbidity and mortality in infants without extensive comorbidities during and just after elective laparoscopic procedures seem limited, indicating that the advantages of performing elective laparoscopic OTC for infants with cancer at high risk of gonadal damage may outweigh the anesthetic and surgical risks of laparoscopic surgery in this age group.