Fertility Preservation Options Research Articles

Standardization of Fertility Preservation Discussion Among Pediatric Oncology and Bone Marrow Transplant Patients: A Single Institution Experience.

Purpose: Infertility is an impactful late effect of cancer therapy. Options for fertility preservation exist, however, barriers remain. Within our division, we lacked a standard approach to discussing fertility preservation. Methods: During the time period of 2014-2020, a fertility preservation program was developed with program improvements implemented over time and provider comfort with fertility identified and addressed through educational intervention. To evaluate how our improvements affected frequency of documented reproductive health discussions, 474 pubertal pediatric patients with new oncological diagnoses were reviewed. Descriptive analysis of sociodemographic determinants was performed. Results: One hundred seventy-five patients met inclusion criteria. Racial/ethnic composition was similar in those receiving and not receiving a fertility consult. Although 19.3% of Caucasians pursued fertility preservation, none of the eight African Americans or five Hispanic females did. Division feedback identified a lack of knowledge regarding available fertility preservation options and diagnoses that should prompt this conversation as barriers to the consulting fertility preservation team. Pre- and posteducation assessments demonstrated increased comfort in discussing fertility preservation and knowledge regarding diagnoses at higher risk of infertility. Integration of a standardized fertility preservation process and addressing barriers identified led to a 33.6% increase in fertility discussions. Conclusion: The establishment of a fertility preservation process and team and division-wide education has led to improvement in rates of fertility discussion in pediatric and adolescent and young adult cancer patients. Similar to young adult data, our data suggest that some racial health disparities may exist in the utilization of fertility preservation in the pediatric oncology population.

A review of fertility preservation in patients with breast cancer.

Breast cancer remains the most common cancer diagnosed in women and causes more lost disability-adjusted life years (DALYs) than any other cancer worldwide; however, improvements in therapies have led to increased survival and therefore a new focus on quality of life following treatment. Fertility is an important concern among cancer survivors of reproductive age. The purpose of this article is to contextualize the importance of oncofertility services for women with breast cancer and review options for fertility preservation, including oocyte/embryo cryopreservation, GnRH agonist therapy, and ovarian tissue cryopreservation. We also discuss special considerations for preimplantation genetic testing for women with germline pathogenic mutations associated with breast cancer, as well as issues related to endocrine therapy. Finally, we review barriers to accessing fertility preservation services, including cost of treatment and lack of referral to reproductive care providers or fertility preservation programs.

How long can oocytes be frozen with vitrification and still produce competent embryos? A series of six cases.

Cryopreservation of oocytes is a relatively new and valuable option for fertility preservation. The duration since vitrification of embryos may be associated with a lower likelihood of success. We do not know how long the oocytes can be vitrified to produce viable pregnancies. We present six cases in which oocytes were vitrified for >10 years for social freezing or cancer. Two patients returned after 11 years, one after 12 years, and one returned after 13 years to use their vitrified oocytes for pregnancy. Four singleton live births were recorded. The two remaining patients returned after 13 years and again after 14 and 15 years, respectively, and failed to conceive. This has raised the burden of the literature on oocyte vitrification for more than 10 years. Oocyte vitrification is an effective option for long-term fertility preservation in women.

Fertility Preservation for Adolescent and Young Adult Transmen: A Case Series and Insights on Oocyte Cryopreservation.

BackgroundThe opportunity for fertility preservation in adolescent and young adult (AYA) transmen is growing. Many AYA transmen desire future biologic children and are interested in ways to preserve fertility through oocyte cryopreservation prior to full gender affirmation, yet utilization of oocyte cryopreservation remains low. Additionally, standard practice guidelines currently do not exist for the provision of oocyte cryopreservation to AYA transmen. Our objective was to review our experience with oocyte cryopreservation in adolescent and young adult transmen in order to synthesize lessons regarding referral patterns, utilization, and oocyte cryopreservation outcomes as well as best practices to establish treatment guidance.MethodsThis is a case series of all AYA transmen (aged 10 to 25 years) who contacted, consulted or underwent oocyte cryopreservation at a single high volume New York City based academic fertility center between 2009 and 2021.ResultsForty-four adolescent and young adult transmen made contact to the fertility center over the study period. Eighty percent (35/44) had a consultation with a Reproductive and Endocrinology specialist, with a median age of 16 years (range 10 to 24 years) at consultation. The majority were testosterone-naive (71%, 25/35), and had not pursued gender affirming surgery (86%, 30/35). Expedited initiation of testosterone remained the most commonly cited goal (86%, 30/35). Fifty-seven percent (20/35) pursued oocyte cryopreservation. Ninety-five percent (19/20) underwent successful transvaginal oocyte aspiration, with a median of 22 oocytes retrieved and 15 mature oocytes cryopreserved. There were no significant adverse events. At time of review, no patient has returned to utilize their cryopreserved oocytes.ConclusionsOocyte cryopreservation is a safe fertility preservation option in AYA transmen and is an important aspect of providing comprehensive transgender care. Insights from referral patterns, utilization, and oocyte cryopreservation outcomes from a single center’s experience with adolescent and young adult transmen can be integrated to identify lessons learned with the goal of providing transparency surrounding the oocyte cryopreservation process, improving the education and comfort of patients and providers with fertility preservation, and easing the decision to pursue an oocyte cryopreservation cycle in parallel to gender-affirmatory care.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Mapping Accessibility to Fertility Preservation for Trans Masculine Individuals in The Netherlands.

Purpose: Since 2014 in The Netherlands, sterilization is no longer required for legal gender affirmation. Access to fertility preservation (FP) options is indispensable to grant equal reproductive rights to this population. This study aims to map existing literature on barriers and enabling factors for trans masculine individuals to access FP in The Netherlands after 2014. Methods: A scoping review method was conducted, including a database and a hand search complemented with informal consultations. Literature between 2014 and 2021 was searched. Results: A total of 38 peer-reviewed articles and 22 complementary gray literature sources were retrieved. Thematic analysis identified seven common themes: biological, psychological, training, language, law and legislation, economic, and sociocultural. The themes were clustered as patient-, health care provider (HCP)- and environment-related. Conclusion: The Netherlands offers progressive legislation and accommodating insurance agreements that favor FP for trans masculine individuals. However, the current readiness of HCPs to provide adapted and tailored care is arguable, and the capacity to access appropriate health services for trans masculine individuals is largely nonexistent outside of highly specialized health institutions. The implementation of both formal and informal education training programs for HCPs on transgender and gender diverse health needs-as well as inclusive language use-could benefit this community at large.

Development of a questionnaire to evaluate female fertility care in pediatric oncology, a TREL initiative

BackgroundCurrently the five-year survival of childhood cancer is up to 80% due to improved treatment modalities. However, the majority of childhood cancer survivors develop late effects including infertility. Survivors describe infertility as an important and life-altering late effect. Fertility preservation options are becoming available to pre- and postpubertal patients diagnosed with childhood cancer and fertility care is now an important aspect in cancer treatment. The use of fertility preservation options depends on the quality of counseling on this important and delicate issue. The aim of this manuscript is to present a questionnaire to determine the impact of fertility counseling in patients suffering from childhood cancer, to improve fertility care and evaluate what patients and their parents or guardians consider good fertility care.MethodsWithin the framework of the EU-Horizon 2020 TREL project, a fertility care evaluation questionnaire used in the Netherlands was made applicable for international multi-center use. The questionnaire to be used at least also in Lithuania, incorporates patients’ views on fertility care to further improve the quality of fertility care and counseling. Results evaluate fertility care and will be used to improve current fertility care in a national specialized pediatric oncology center in the Netherlands and a pediatric oncology center in Lithuania.ConclusionAn oncofertility-care-evaluation questionnaire has been developed for pediatric oncology patients and their families specifically. Results of this questionnaire may contribute to enhancement of fertility care in pediatric oncology in wider settings and thus improve quality of life of childhood cancer patients and survivors.

How Accurate Is Oncologist Knowledge of Fertility Preservation Options, Cost, and Time in Female Adolescents and Young Adults?

Purpose: Often cited barriers to fertility preservation (FP) among female adolescent and young adult (AYA) cancer patients include cost and time. We hypothesized that oncologists overestimate the time and costs required for female FP. Methods: We distributed an electronic survey to physicians in oncology-related departments. The survey assessed the knowledge and utilization of gonadotoxic therapies, FP options and requirements, and FP referral patterns. Student's t, Fisher's exact, ANOVA, and Wilcoxon signed-rank tests were used for continuous variables as appropriate; the chi-squared test was used for categorical variables. Results: Among respondents who reported prescribing gonadotoxic agents to AYAs (n = 38), 79% reported often/always discussing FP options, while only half referred to a reproductive specialist often/always. A smaller proportion of pediatric oncologists discussed FP often/always (p = 0.04) and most referred <25% of patients to a reproductive specialist; however, the majority of other specialists referred ≥75% of patients to a reproductive specialist (p = 0.001). While most respondents accurately estimated the time required to complete FP, the majority overestimated the cost of an FP procedure. Knowledge of FP options was inconsistent, with 63.2% reporting that suppression of the hypothalamic-pituitary-ovarian-axis is an option for FP, with 82.6% of these classifying it as standard of care. Conclusions: With variation across specialties, most oncology specialists prescribing gonadotoxic therapies for AYA females discuss FP, while a smaller proportion refer patients for FP. Despite relative accuracy in estimating the time required for FP, they overestimate costs of FP. Educational curricula related to FP are necessary across oncology specialties, especially pediatric oncology.

The Experience of Fertility Preservation in a Single Tertiary Center in Korea.

ObjectiveOocyte (OC), embryo (EC), and ovarian tissue cryopreservation (OTC) are options for fertility preservation (FP) before going through gonadotoxic cancer treatment, or anticipated fertility decline in benign ovarian diseases, or for planned OC. The aim of this study is to report outcomes of FP in a single tertiary hospital in Korea.MethodsThis is a retrospective study of OC, EC, and OTC cycles. All patients who visited or were referred to the infertility clinic at the Department of Obstetrics and Gynecology for the purpose of FP between 2010 and October 2021 were included.ResultsA total of 564 controlled ovarian stimulation cycles were conducted in 416 women. Three hundred fifty-seven women underwent 494 OC cycles. Most patients were diagnosed with breast cancer (22.4%), followed by endometriomas (21.9%), and then by planned OC (20.7%). Cases of OC have increased over the years, peaking at 109 cycles in 2019 compared to one in 2010. Fifty-nine women underwent 70 EC cycles, and breast cancer (50.8%) was the most common indication. Repetitive OC and EC cycles were undergone in 92 and 9 women, respectively (mean number of repetition, 1.37 and 1.19 times in OC and EC, respectively), yielding a maximum number of 33 oocytes or 23 embryos being cryopreserved per patient. The utilization rate was 3.1% (11/357) in OC and 16.9% (10/59) in EC. Twenty-six women underwent OTC, and gynecologic cancer was the most common indication (9/26, 34.6%). One woman had the cryopreserved ovarian tissue retransplanted and successfully generated embryos.ConclusionOC, EC, and OTC are possible options for preserving fertility, and these opportunities should be provided for women at risk of fertility decline or those who are eager to protect their future fertility. This is the first report on long-term FP outcomes in a single tertiary center in Korea. We expect that there will be more cases over the years and more women returning to use their gametes or embryos for pregnancy.

Reproductive Considerations for Patients with Early-Onset Breast Cancer.

Early-onset breast cancer presents various challenges in regard to reproductive health. This review examines the current data pertaining to issues such as fertility preservation, preimplantation genetics, the impact of chemotherapy and endocrine therapy, contraception, and pregnancy in the young breast cancer population. Many breast cancer treatments such as chemotherapy and endocrine therapy can be gonadotoxic or teratogenic. Multiple fertility preservation options are now available to young breast cancer patients, including embryo and oocyte preservation, ovarian tissue preservation, and ovarian suppression with GnRH agonists. In patients with known cancer germline mutations, preimplantation genetic testing is an option. Fertility preservation and other reproductive services are expanding and offer great promise to the early-onset breast cancer community. Providers must be knowledgeable about the various options in order to better empower patients.

Male fertility preservation and restoration strategies for patients undergoing gonadotoxic therapies†.

Medical treatments for cancers or other conditions can lead to permanent infertility. Infertility is an insidious disease that impacts not only the ability to have a biological child but also the emotional well-being of the infertile individuals, relationships, finances, and overall health. Therefore, all patients should be educated about the effects of their medical treatments on future fertility and about fertility preservation options. The standard fertility preservation option for adolescent and adult men is sperm cryopreservation. Sperms can be frozen and stored for a long period, thawed at a later date, and used to achieve pregnancy with existing assisted reproductive technologies. However, sperm cryopreservation is not applicable for prepubertal patients who do not yet produce sperm. The only fertility preservation option available to prepubertal boys is testicular tissue cryopreservation. Next-generation technologies are being developed to mature those testicular cells or tissues to produce fertilization-competent sperms. When sperm and testicular tissues are not available for fertility preservation, inducing pluripotent stem cells derived from somatic cells, such as blood or skin, may provide an alternative path to produce sperms through a process call in vitro gametogenesis. This review describes standard and experimental options to preserve male fertility as well as the experimental options to produce functional spermatids or sperms from immature cryopreserved testicular tissues or somatic cells.

Why are women considering ovarian tissue cryopreservation to preserve reproductive and hormonal ovarian function? A qualitative study protocol

IntroductionCurrent fertility preservation options available to women are oocyte cryopreservation (egg freezing) or embryo cryopreservation. A newer procedure, ovarian tissue cryopreservation (OTC), has become available in some centres, which offers...

133 Investigating the Utilization Rate of Fertility Preservation Services Amongst Transgender and Gender Diverse Patients

OBJECTIVES/GOALS: Fertility preservation (FP) allows transgender and gender diverse (TGD) patients undergoing gender-affirming therapy to pursue genetic parenthood. Barriers to care exist leading to its underutilization; while these barriers to care have been investigated, the true utilization rates of FP services by TGD patients are unknown. METHODS/STUDY POPULATION: This study includes a retrospective chart review of adult and pediatric patients from Mayo Clinics Transgender and Intersex Specialty Care Clinic who have provided research authorization. We will assess if FP was discussed and review if the patients proceeded to make appointments with either the Department of Reproductive Endocrinology &amp; Infertility or the Department of Urology. FP terms include semen cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. Patient demographic data will be collected to determine associations between utilization rate and age, sex recorded at birth, gender identity, race, ethnicity, and variables related to socioeconomic determinants of health. RESULTS/ANTICIPATED RESULTS: We hypothesize that the rate of FP utilization will be higher for patients who begin to affirm their gender at the age of 25 or older, and for those seeking feminization treatment in comparison to pre-pubescent adolescents, young adults, and transgender men. Of FP options, semen cryopreservation will be most utilized, followed by oocyte cryopreservation; both will be more utilized than embryo cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, and ovarian tissue cryopreservation. Employment, and insurance status and coverage, will play a role in FP service utilization after initial consult. This study was approved by Mayo Clinics Institutional Review Board. Data on N=611 patients is expected to be abstracted and analyzed prior to Translation 2022. DISCUSSION/SIGNIFICANCE: This study will be one of the first to examine the rate of FP utilization by TGD patients with respect to the age and timing of gender-affirming therapy initiation. Understanding the rate of utilization of FP services will allow for the creation of age-appropriate education materials for TGD patients pursuing gender affirmation and FP at Mayo Clinic.

Changing the Narrative, Starting With Us

Infertility can affect anyone, including Black women who, contrary to popular belief, are most likely to suffer from infertility, less likely to seek fertility care, and more likely to delay or completely forgo fertility treatment (Chin et al Paediatr Perinat Epidemiol 29(5):416-25, 5). These trends are likely fueled by deep-rooted stigma generated from a multitude of origins. Some black women may feel uncomfortable discussing their experience with infertility due to the pervasive stereotype that Black women are hyper-fertile (Ceballo et al Psychol Women Q 39(4):497-511, 20). This stereotype also has important implications within the medical field, in which provider implicit bias may affect referrals and treatment plans, further contributing to stratified reproduction (Chapman et al J Gen Intern Med 28(11):1504-10, 15, FitzGerald and Hurst BMC Med Ethics 18(1):19, 16). It is time for the medical community to shift our focus to what we can change, starting with how we perceive the narrative. In order to effect change, providers should first become and remain aware of racial/ethnic disparities within reproduction. We can make a concerted effort to effectively counsel Black women about their fertility and future childbearing goals, as well as strive to debunk false racial/ethnic fertility stereotypes with medical evidence. We should actively work to understand our biases, where they stem from, and how to resolve them. We must aim to always provide respectful, equitable, and consistent care, especially when deciding how to counsel someone regarding fertility preservation and infertility treatment options. In sum, we can approach solving this complicated racial-ethnic gap in health equity by taking small intentional and parallel steps, starting now.

Navigating Human Immunodeficiency Virus and Primary Care Concerns Specific to the Transgender and Gender-Nonbinary Population.

Human immunodeficiency virus (HIV) prevention and treatment remain critically important to outpatient care among transgender and gender-nonbinary individuals. Epidemiologically, trans men and trans women are significantly more likely to have HIV compared with all adults of reproductive age. Here, we provide an overview of unique primary care considerations affecting transgender and gender-nonbinary individuals, including screening and treatment of HIV and other sexually transmitted infections as well as cancer screening and fertility preservation options. We also seek to review current literature and clinical practice guidelines related to drug–drug interactions between antiretroviral therapy (ART) and gender-affirming hormonal therapy (GAHT). In short, integrase strand transfer inhibitor–based therapy is not expected to have significant drug interactions with most GAHT and is preferred in most transgender individuals, including those on GAHT. Clinicians should also remain aware of current GAHT regimens and consider tailoring ART and GAHT to reduce cardiovascular and other risk factors.

Short-Term Hypothermic Holding of Mouse Immature Testicular Tissue Does Not Alter the Expression of DNA Methyltransferases and Global DNA Methylation Level, Post-Organotypic Culture.

IntroductionCryopreservation of immature-testicular-tissue (ITT) prior to gonadotoxic treatment, while experimental, is the only recommended option for fertility preservation in prepubertal boys. The handling and manipulation of ITT prior to banking could influence the functionality, genetic and epigenetic integrity of cells.ObjectivesTo investigate the impact of length of hypothermic holding of mouse ITT on the relative mRNA expression of the DNA methyltransferases (DNMTs) and global DNA methylation, post 14-days of organotypic culture.MethodsITT from 6-day old mice were handled at hypothermic temperature (4 °C) for 6 and 24 h prior to 14-days organotypic culture. Relative mRNA expression of Dnmt1, Dnmt3a, and Dnmt3b along with global DNA methylation was measured from the cultured ITT.ResultsNo significant variation in the expression of Dnmt1, Dnmt3a, and Dnmt3b was observed in relation to varying holding time periods used. Further, global DNA methylation was comparable between 0, 6 and 24 h holding groups.ConclusionsShort-term holding of ITT at 4 °C does not affect the DNA methylation process post organotypic culture. While fully acknowledging the limitations of this approach in the mouse model, the results we presented in this report will be of significant interest to the field.

Fertility Desire and Motivation Among Individuals with Gender Dysphoria: A Comparative Study

Despite receiving Gender-Affirming Hormone Therapy or Gender-Affirming Surgery, which may adversely impact their fertility, people with Gender Dysphoria (GD) may desire to form families. In this study, we aimed to quantitatively display fertility desire from the perspective of these individuals, despite all the legal challenges they face. The single center, cross-sectional comparative study included individuals with GD and cisgender volunteers. A Sociodemographic Data Form, the Fertility Desire Data Form, the Childbearing Motivations Scale and the Fertility Desire Scale were used. Of the 414 participants, 171 were individuals with GD (110 FtM; 61 MtF) and 243 were cisgender volunteers (142 cis-males; 101 cis-females). While 22% of the people with GD stated that they had regrets about not undergoing fertility preservation, 16% stated that they would like this process if it were legal. People with GD, particularly MtF, want to have children more than cisgenders. Moreover, people with MtF exhibited less negative motivations toward becoming parents, despite having reservations regarding the socioeconomic aspect of parenthood. Our findings indicate that fertility desire in people with GD is not less in comparison to cisgender people. Healthcare professionals should not forget to offer fertility preservation options as part of clinical practice before Gender-Affirming Therapy.

51. Feasibility, Acceptability, and Preliminary Efficacy of AFFRMED (Aid For Fertility-Related Medical Decisions), a Web-Based Fertility Decision Aid for Transgender and Non-binary Youth and their Parents

Fertility preservation (FP) offers transgender and non-binary (TNB) youth the option to freeze gametes for future use. Decisions about FP are complex because: (1) there is limited and conflicting research on the effects of gender-affirming medical interventions on fertility, (2) pediatric FP options and assisted reproductive technologies are rapidly evolving, (3) TNB youth must consider parenting desires during a developmental stage at which they may not be ready to engage in family building discussions, and (4) impaired fertility affects future quality of life rather than current functioning.

How fertility preservation guidelines have progressed worldwide: Potential implications and inspiration

Abstract To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women's and Children's Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.

Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series. The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft. The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model. The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes. Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation.