Multidisciplinary consensus on the criteria for fertility preservation in cancer patients.

Infertility is one of the main sequelae of cancer and its treatment in both children and adults of reproductive age. It is, therefore, essential that oncologists and haematologists provide adequate information about the risk of infertility and the possibilities for its preservation before starting treatment. Although many international clinical guidelines address this issue, this document is the first Spanish multidisciplinary guideline in paediatric and adult oncological patients. Experts from the Spanish Society of Medical Oncology, the Spanish Fertility Society, the Spanish Society of Haematology and Haemotherapy, the Spanish Society of Paediatric Haematology and Oncology and the Spanish Society of Radiation Oncology have collaborated to develop a multidisciplinary consensus.

How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience.

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

INTRODUCTION: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation. METHODS: Retrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1-2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition). RESULTS: High-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35). CONCLUSIONS: Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation.

Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes.

Frozen-thawed human ovarian tissue endures large-scale follicle loss in the early post-grafting period, characterized by hypoxia lasting around 7 days. Tissue revascularization occurs progressively through new vessel invasion from the host and neoangiogenesis from the graft. Such reoxygenation kinetics lead to further potential damage caused by oxidative stress. The aim of the present manuscript is to provide a systematic review of proangiogenic growth factors, hormones and various antioxidants administered in the event of ovarian tissue transplantation to protect the follicle pool from depletion by boosting revascularization or decreasing oxidative stress. Although almost all investigated studies revealed an advantage in terms of revascularization and reduction in oxidative stress, far fewer demonstrated a positive impact on follicle survival. As the cascade of events driven by ischaemia after transplantation is a complex process involving numerous players, it appears that acting on specific molecular mechanisms, such as concentrations of proangiogenic growth factors, is not enough to significantly mitigate tissue damage. Strategies exploiting the activated tissue response to ischaemia for tissue healing and remodelling purposes, such as the use of antiapoptotic drugs and adult stem cells, are also discussed in the present review, since they yielded promising results in terms of follicle pool protection.

Challenging cases in oncofertility: insights from a national specialized e-meeting for fertility preservation specialists.

PURPOSE: To determine the use of a new specialized E-Meeting for Complex Cases in Oncofertility by fertility preservation specialists (FPSs) MATERIAL AND METHODS: We present 3 years of activity of the E-Meeting for Complex Cases in Oncofertility, a new tool created in September 2016 which allows national oncofertility experts to share viewpoints about challenging cases for which they do not have experience or sufficient data in order to provide them an emergency advice within 48 h. Second, a survey was conducted to evaluate the use of this e-meeting for participating FPSs. RESULTS: One hundred and four experts have joined the e-meeting since its set-up, and 109 challenging cases have been submitted. The mean age of the patients was 22.4 ± 8.9 years, and 87.0% were female. Each submitted case received on average of 1.8 ± 1.1 different strategies for FP and the opinions of 7.1 ± 3.4 experts. Among the FPSs who submitted cases, seeking opinions from other FPSs allowed them to confirm their care plan (N = 49, 84.4%), to offer different options to their patients (N = 34, 58.6%), and to compare their practices with those of other specialists (N = 23, 39.6%). All respondents reported a self-perceived improvement in their practice of oncologic FP (n = 80, 100.0%). CONCLUSION: Specific attention should be paid to challenging cases for which the experiences of only a few individuals exist. Enhancing communication between FPSs through oncofertility networks, pooling experiences, and collecting the most complex cases is required to improve the management of these patients.

Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial.

PURPOSE: To determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield. METHODS: Open-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18-44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER-) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes. RESULTS: Forty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =-2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups. CONCLUSIONS: Tamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group. TRIAL REGISTRATION: NCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled).

Fertility preservation in patients with BRCA mutations or Lynch syndrome.

Guidelines and expert consensus are lacking on fertility preservation in BRCA mutation carriers and in patients with Lynch syndrome. The safety of fertility preservation in this setting is still a topic of debate and multiple factors need to be carefully considered. The aim of this review was to analyze the reproductive potential of women harboring a genetic mutation affecting the DNA repair system and explore the efficacy and safety of existing fertility preservation strategies in these patients.

Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

Fertility Preservation: The Challenge of Freezing and Transplanting Ovarian Tissue.

Cancer treatments are increasingly effective, but can result in iatrogenic premature ovarian insufficiency. Ovarian tissue cryopreservation is the only option available to preserve fertility in prepubertal girls and young women who require immediate chemotherapy. Ovarian tissue transplantation has been shown to restore hormonal cycles and fertility, but a large proportion of the follicle reserve is lost as a consequence of exposure to hypoxia. Another crucial concern is the risk of reimplanting malignant cells together with the grafted tissue. In this review, the authors advance some challenging propositions, from prevention of chemotherapy-related gonadotoxicity to ovarian tissue cryopreservation and transplantation, including the artificial ovary approach.

Imaging modalities in fertility preservation in patients with gynecologic cancers.

Fertility preservation is an integral component of clinical decision-making and treatment design. However, the selection criteria on imaging for patients eligible for fertility preservation is still unclear. The present review aimed to summarize the main findings reported in both the literature and international guidelines on the role of imaging in the selection of patients for fertility preservation. A search strategy was developed and applied to PubMed, Scopus, Web of Science, and EMBASE to identify previous citations reporting imaging and fertility preservation in patients with gynecological cancer. We also retrieved the published guidelines on the eligibility criteria for fertility-sparing treatment of gynecological neoplasms. A description of the internal multidisciplinary guidelines, clinically in use in our institution, is provided with representative clinical cases. The literature review revealed 1291 articles and 18 of these were selected for the analysis. Both ultrasound and MRI represented the primary imaging methods for selecting patients for fertility preservation in cervical and endometrial cancers. Eligibility criteria of fertility-sparing management in patients with cervical cancer were: tumor size <2 cm, tumor distance from the internal os >1 cm, and no parametrium invasion. For patients with endometrial cancer, these included no myometrial and cervical stroma invasion. Both ultrasound and MRI play a key role in characterizing adnexal masses. These modalities provide a useful tool in identifying small ovarian lesions, thus key in the surveillance of patients after fertility sparing surgery. However, efficacy in excluding disease beyond the ovary remains limited. This review provides an update of the literature and schematic outline for the counseling and management of patients with the desire for fertility preservation.

Current Fertility Preservation Options for Female Patients With Hodgkin Lymphoma.

IMPORTANCE: Many adolescents and young adults diagnosed with Hodgkin lymphoma (HL) experience disease progression requiring high-dose alkylating salvage therapy, which often results in permanent infertility. OBJECTIVE: The aim of this report is to discuss fertility preservation options in female patients with consideration of chemotherapeutic agents in HL. EVIDENCE ACQUISITION: An electronic literature review was performed utilizing a combination of the terms "Hodgkin lymphoma," "fertility preservation," "ovarian tissue cryopreservation," "oocyte cryopreservation," "embryo cryopreservation," and "gonadotropin-releasing hormone agonist." References and data from identified sources were searched and compiled to complete this review. RESULTS: Initial treatment of HL is often nonsterilizing; however, salvage therapy and conditioning for stem cell transplantation confer significant gonadotoxicity. Established fertility preservation options for pubertal females include embryo cryopreservation and oocyte cryopreservation. These options are contraindicated within 6 months of receipt of chemotherapy. Ovarian tissue cryopreservation is an option for patients who require salvage therapy within 6 months of first-line therapy. CONCLUSIONS: Timing and choice of fertility preservation techniques depends on planned first-line chemotherapy and response to treatment. In patients initially treated with low-risk chemotherapy, it is reasonable to defer invasive fertility techniques until treatment failure; however, upfront fertility preservation should be considered in patients planning to undergo primary treatment with high-risk therapy.

Evaluation of Reported Fertility Preservation Counseling Before Chemotherapy Using the Quality Oncology Practice Initiative Survey.

Importance: The opportunity to discuss fertility preservation is essential for patients of reproductive age with newly diagnosed cancer before the initiation of treatment. Objective: To identify factors associated with fertility preservation counseling among patients of reproductive age before initiating chemotherapy. Design, Setting, and Participants: This cross-sectional study used data obtained from the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative, an oncologist-led quality assessment program that surveys approximately 400 oncology practices biannually, from January, 2015, to June, 2019. Main Outcomes and Measures: The primary outcome was whether reproductive risks were discussed before initiation of chemotherapy. Multivariate logistic regression was performed to identify factors associated with fertility preservation counseling, controlling for age, sex, race/ethnicity, cancer type, year of study, region, clinic type (academic vs private), annual clinic volume, and rates of insurance coverage. Results: Among the 6976 patients of reproductive age (3571 men [51%]; mean (SD) age, 42.5 [7.1] years), with reproductive age ranging from 18 to 40 years for 3405 women and from 18 to 50 years for 3571 men, clinics reported that 3036 of 6976 patients (44%) received counseling regarding the risk of infertility associated with chemotherapy. Women were more likely to be informed (1912 of 3405 [56%]) compared with men (1126 of 3571 [32%]) (P < .001). Factors associated with reduced likelihood of fertility risk discussion included male sex (odds ratio [OR], 0.73; 95% CI, 0.60-0.90), increasing age (OR, 0.93; 95% CI, 0.92-0.94), private practice setting (OR, 0.70; 95% CI, 0.53-0.93), and lack of multidisciplinary team planning (OR, 0.54; 95% CI, 0.41-0.70). Factors associated with increased likelihood of fertility risk discussion included having breast cancer (OR, 1.39; 95% CI, 1.12-1.73) and lymphatic or hematopoietic cancers (OR, 1.79; 95% CI, 1.33-2.40), participating in each subsequent study year (OR, 1.16; 95% CI, 1.08-1.24), receiving care in an academic clinic (OR, 1.45; 95% CI, 1.05-2.01), and being a practice offering clinical trial enrollment (OR, 1.60; 95% CI, 1.13-2.29). States with legislatively mandated coverage of fertility preservation had significantly higher rates of fertility risk discussion compared with states without legislation (48.6% vs 39.6%, P < .001). Conclusions and Relevance: The findings suggest that clinicians are more likely to counsel younger patients and female patients about reproductive risks before initiation of chemotherapy. State laws mandating fertility preservation coverage may be associated with improved frequency of fertility counseling before chemotherapy. Further awareness and implementation of ASCO guidelines appear to be needed to improve rates of fertility risk discussion and referrals to fertility specialists before chemotherapy.

Simple vaginal trachelectomy in women with early-stage low-risk cervical cancer who wish to preserve fertility: the new standard of care?

OBJECTIVE: There is a trend toward less radical surgery in women with small-volume disease who wish to preserve fertility. The objective of our study was to evaluate the oncologic and obstetrical outcome of simple vaginal trachelectomy and lymph node assessment in patients with low-risk early-stage cervical cancer (<2 cm). METHODS: From May 2007 to January 2020, 50 patients underwent a simple vaginal trachelectomy/conization with laparoscopic sentinel lymph node mapping±complete pelvic node dissection. Patients underwent loop electrocautery excision (LEEP), cone/cervical biopsies, or simple trachelectomy. A preoperative pelvic MRI with gadolinium contrast was systematically performed in all cases. The size of the lesion was established by review of the LEEP, cone or trachelectomy specimen, MRI, and clinical examination. Data was collected prospectively in a computerized database. Descriptive statistics and the Kaplan-Meier estimate were used for analysis. RESULTS: The median age was 29 years (range: 21-44) and 35 (70%) patients were nulliparous. As per FIGO 2009 classification, 11 patients had stage IA1 with lymphovascular space invasion (LVSI), 13 patients had stage IA2, and 26 patients had stage IB1. Twenty-six patients had squamous histology, 20 patients adenocarcinoma, and four patients other histologies. On final pathology, lymph nodes were negative in 46 patients (92%), three patients had isolated tumor cells, and one patient had micrometastasis. Thirty patients (60%) had either no residual disease in the trachelectomy specimen (22) or residual dysplasia only (eight). With a median follow-up of 76 months (range: 1-140), only one local recurrence occurred which was treated initially with chemoradiation. She recurred again locally and underwent a pelvic exenteration: the patient progressed again and died of disease. The 5-year progression-free survival and overall survival was 97.9% and 97.6%, respectively. There were 40 pregnancies: five (12.5%) ended in the first trimester, one (2.5%) in the second trimester, and three (7.5%) were late preterm: all the others (30 or 75%) delivered >36 weeks and one pregnancy is ongoing. CONCLUSION: Simple trachelectomy/conization and lymph node assessment is an oncologically safe fertility-preserving surgery in well-selected patients with low-risk early-stage cervical cancer (<2 cm). Obstetrical outcomes are comparable to the general population.

Establishing an Institutional Gonadal Tissue Cryopreservation Protocol for Patients with Differences of Sex Development.

PURPOSE: Many individuals with differences of sex development experience subfertility. We describe a novel gonadal tissue cryopreservation protocol for those individuals. MATERIALS AND METHODS: Before 2018 patients with differences of sex development electing gonadal tissue cryopreservation were enrolled in a cancer focused protocol. Thereafter, our hospital developed a protocol specifically for these patients undergoing gonadectomy due to neoplasia risk. Protocol development steps and procedures are reported. A retrospective chart review was conducted for patient characteristics and cryopreservation choices. RESULTS: During the institutional review board approval process there were multidisciplinary meetings with stakeholders. The main concerns discussed included preoperative counseling, pathological evaluation and final tissue disposition. Detailed multidisciplinary preoperative counseling is provided regarding potential gonadal tissue cryopreservation for patients undergoing gonadectomy. For enrolled patients the gonad is bisected after removal, with half being sent to pathology and half being processed for cryopreservation. If neoplasia is noted, cryopreserved tissue is recalled for further pathological analysis. Postoperative counseling is performed after pathology results are available, and the final gonadal tissue cryopreservation decision is made. During the study period 7 patients with 5 diagnoses and a median age of 10.99 years (IQR 1.29 to 14.84) elected to attempt gonadal tissue cryopreservation. Of the patients 4 (57%) had germ cells and elected to store tissue. CONCLUSIONS: Gonadal tissue cryopreservation at the time of gonadectomy is feasible for patients with differences of sex development at risk for gonadal neoplasia. The protocol described represents a template for institutions wishing to offer gonadal tissue cryopreservation to patients electing gonadectomy. More than half of patients thus far have cryopreserved gonadal tissue.

The pediatric patient and future fertility: optimizing long-term male reproductive health outcomes.

Globally, male factor infertility accounts for 20%-70% of couples struggling to conceive. Certain male pediatric developmental conditions, such as cryptorchidism, hypospadias, testicular and other childhood cancers, infections, and pediatric varicocele have been associated with future infertility. Early fertility preservation, especially in those with pending chemotherapy or genetic conditions such as Klinefelter syndrome, should be strongly considered in patients expected to experience testicular loss. Although optimal treatment timing may be unknown owing to a paucity of long-term prospective studies, early diagnosis and targeted treatment may optimize fertility potential in adulthood.

Association between hospital surgical volume and perioperative outcomes of fertility-sparing trachelectomy for cervical cancer: A national study in the United States.

OBJECTIVE: To examine the association between hospital surgical volume and perioperative outcomes for fertility-sparing trachelectomy performed for cervical cancer. METHODS: This is a population-based retrospective observational study utilizing the Nationwide Inpatient Sample from 2001 to 2011. Women aged ≤45 years with cervical cancer who underwent trachelectomy were included. Annualized hospital surgical volume was defined as the average number of trachelectomies a hospital performed per year in which at least one case was performed. Perioperative outcomes were assessed based on hospital surgical volume in a weighted model, specifically comparing the top-decile centers to the lower volume centers. RESULTS: There were a total of 815 trachelectomies performed at 89 centers, and 76.4% of the trachelectomy-performing centers had a minimum surgical volume of one trachelectomy per year. The top-decile group had a higher rate of lymphadenectomy performance compared to the lower volume group (96.4% versus 82.4%, odds ratio [OR] 5.65, 95% confidence interval [CI] 2.81-11.4, P < 0.001). There was a significant inverse linear association between annualized surgical volume and the number of perioperative complications (P = 0.020). The top-decile group also had a lower rate of perioperative complications (9.7% versus 21.0%, P < 0.001) and prolonged hospital stay ≥7 days (2.0% versus 6.5%, P = 0.006) compared to the lower volume group. In a multivariable analysis, the top-decile group had a 65% relative decrease in perioperative complication risk compared to the lower volume group (adjusted-OR 0.35, 95%CI 0.20-0.59, P < 0.001). CONCLUSION: Fertility-sparing trachelectomy for young women with cervical cancer is a rare surgical procedure; <90 centers performed this procedure from 2001 to 2011 and most hospitals perform a small number of cases annually. Higher hospital surgical volume for trachelectomy may be associated with reduced perioperative morbidity.

Expanding Urgent Oncofertility Services for Reproductive Age Women Remote from a Tertiary Level Fertility Centre by Use of Telemedicine and an On-site Nurse Navigator.

The objective of this study was to examine a 1-year pilot program aimed at increasing access to fertility preservation (FP) information and services for reproductive-age women newly diagnosed with cancer at a centre geographically remote from a tertiary fertility clinic. An oncofertility nurse navigator (ONN) position was created within the regional cancer centre with the goals of (1) improving local physician knowledge of FP and FP services and (2) improving patient access to FP counselling and services. The ONN identified all women diagnosed with cancer requiring treatment that could impact their fertility and discussed FP options with them and their physicians. As part of a comprehensive program aimed at facilitating access to FP services, the ONN arranged consultations with fertility specialists via telemedicine and coordinated satellite cycle monitoring with a local gynaecologist in order to minimize travel. Patients were surveyed about their reproductive plans, decision-making around FP and experiences with the program. Physicians were surveyed about their engagement with FP services, barriers to FP access and satisfaction with the program. Twenty-two women were eligible for FP during the year-long pilot program. All participated in the study. The most common diagnoses were breast and cervical cancer. At the time of diagnosis, 36.4% of women had no biological children and 68.2% did not desire (more) children. Four women had an FP consultation, and two proceeded with oocyte or embryo cryopreservation. At the end of the pilot program, more physician respondents often or always discussed FP with their patients, stated they frequently refer for FP consultations and stated their patients could obtain FP services in a timely fashion. An ONN within a cancer centre remote from tertiary fertility care can enable access to FP services with minimal need for travel by using local gynaecologic expertise and telemedicine.

Preserving fertility in female patients with hematological malignancies: a multidisciplinary oncofertility approach.

Oncofertility is a new interdisciplinary field at the intersection of oncology and reproductive medicine that expands fertility options for young cancer patients. The most common forms of hematological malignancies that occur in girls and young women and therefore necessitate oncofertility care are acute lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, and Hodgkin's lymphoma. Aggressive gonadotoxic anticancer regimens including alkylating chemotherapy and total body irradiation are used often in treating girls and young women with hematological malignancies. The risks of gonadotoxicity and subsequent iatrogenic premature ovarian insufficiency and fertility loss depend mainly on the type and stage of the disease, dose of anticancer therapy as well as the age of the patient at the beginning of treatment. To avoid or at least mitigate the devastating complications of anticancer therapy-induced gonadotoxicity, effective and comprehensive strategies that integrate different options for preserving and restoring fertility ranging from established to experimental strategies should be offered before, during, and after chemotherapy or radiotherapy. A multidisciplinary approach that involves strong coordination and collaboration between hemato-oncologists, gynecologists, reproductive biologists, research scientists, and patient navigators is essential to guarantee high standard of care.