Fertility Preservation Counseling Research Articles

Pregnancy and pregnancy outcomes after hematopoietic stem cell transplantation in childhood: a cross-sectional survey of the EBMT Pediatric Diseases Working Party.

What are the characteristics of patients with conceptions transplanted in childhood and adolescence? Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients <18 years old before their first transplantation who received HCT between 1995 and 2016 and were in the European Society for Blood and Marrow Transplantation (EBMT) registry. Adoptions were excluded from the analysis. Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7-18) years, and the median age at declared conception was 25.0 (range: 16.3-38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8-27) years, with a median time after transplant of 10.7 (IQR: 6.6-15.4) years. Compared with the mean age of healthy women at their first child's birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. In the EBMT pediatric dataset, the age at last follow-up or death was <17 years for 75% of the patients, therefore a longer follow-up for all patients would be necessary to calculate the cumulative incidence of conception for patients transplanted during childhood and allow all patients to realize their reproductive willingness/potential. Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support. Funding was provided by the 'Stiftung für krebskranke Kinder Regio Basiliensis', Basel, Switzerland. All authors have no conflicts of interest to declare. N/A.

ONCOFERTILITY RESEARCH PITFALL? RECALL BIAS AMONG YOUNG ADULT CANCER SURVIVORS

Oncofertility literature cites recall bias as a pitfall of retrospective surveys(1,2), but limited data exist to quantify this bias(3). Our objective was to assess recall bias by evaluating how well female cancer survivors remember details regarding their cancer diagnoses, oncology treatments, infertility risk factors, and fertility preservation (FP) counseling.

FERTILITY PRESERVATION IN TRANSGENDER MEN AND THE NEED FOR UNIFORM TEMPLATES FOR COMPREHENSIVE COUNSELING: A REVIEW

Data suggest that transgender individuals have similar family building desires as cisgender ones [1]. The ASRM Ethics Committee recommends that all transgender persons have access to fertility services and preservation counseling before gender transition [1]. Although the importance of this is well recognized, there are no standardized templates to guide this counselling. Our objective was to review the literature to assess best practices for the counseling of transgender men who desire gender- affirming surgery.

MP34-05 ESTABLISHING AN ONCOLOGY FERTILITY PRESERVATION PROGRAM – AREAS OF IMPACT

You have accessJournal of UrologyHealth Services Research: Quality Improvement & Patient Safety II (MP34)1 Sep 2021MP34-05 ESTABLISHING AN ONCOLOGY FERTILITY PRESERVATION PROGRAM – AREAS OF IMPACT Jason Huang, Yael Simons, David Dulce, Amaara Babwah, Candice Schwartz, Neeta Venepalli, Rozina Chowdery, Gail S Prins, and Samuel Ohlander Jason HuangJason Huang More articles by this author , Yael SimonsYael Simons More articles by this author , David DulceDavid Dulce More articles by this author , Amaara BabwahAmaara Babwah More articles by this author , Candice SchwartzCandice Schwartz More articles by this author , Neeta VenepalliNeeta Venepalli More articles by this author , Rozina ChowderyRozina Chowdery More articles by this author , Gail S PrinsGail S Prins More articles by this author , and Samuel OhlanderSamuel Ohlander More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002043.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Fertility preservation (FP) services are often underutilized in oncologic care despite the availability of services and expanding advocacy. Ten states, including Illinois, have laws requiring insurance coverage of FP costs for cancer patients. We conducted a quality improvement (QI) initiative to both establish our male FP program among cancer patients and assess the provider-level barriers to doing so, as a collaborative effort to improve patient care. METHODS: Barriers to discussion and utilization of FP services were assessed by surveying oncology providers and holding discussions with social workers and patient care coordinators; the results guided our QI interventions. We identified males diagnosed and treated for cancer at our institution, an urban academic tertiary referral center, between January 2019 and December of 2019 and after a series of QI interventions from September 14, 2020 through February 12, 2021. State mandated FP coverage went into effect January 1, 2020. We retrospectively reviewed patient charts to determine rates of discussion and utilization of FP services. RESULTS: Fourteen of 14 providers surveyed responded. The most common barriers to discussion of FP were knowledge deficits among providers (25% of respondents) and difficulty with documentation (25%); other reasons were assumptions about the patient (22%), perceptions regarding FP (14%), and comfort discussing FP (14%). Our interventions thus included 2 lectures to oncologists and oncology fellows, with an emphasis on guidelines and awareness of our institution’s FP services, and provision of quick reference guides. During our intervention period, our institution transitioned to a new electronic medical record system (EMR) that included a FP referral communication for all new chemotherapy orders. Prior to QI interventions, a total of 205 patients with newly diagnosed and treated cancer were reviewed. 29 (14.1%) of these patients had documented FP counseling and 11 proceeded with cryopreservation. After initiation of our QI interventions, we identified 35 patients meeting inclusion criteria over a 21-week period, and 14 (22.9%) were offered FP services. CONCLUSIONS: Despite recognition of the importance of FP and increasing availability of FP services, significant barriers to access remain, including at the provider level. However, by supplying providers with educational material, patient care can be meaningfully improved. Educating providers outside of fertility specialists is crucial to establishing a FP program for cancer patients. Additional and continued efforts must be applied to assure further improvement in counseling rates and utilization of FP services. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e618-e618 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Huang More articles by this author Yael Simons More articles by this author David Dulce More articles by this author Amaara Babwah More articles by this author Candice Schwartz More articles by this author Neeta Venepalli More articles by this author Rozina Chowdery More articles by this author Gail S Prins More articles by this author Samuel Ohlander More articles by this author Expand All Advertisement Loading ...

BARRIERS TO FERTILITY PRESERVATION IN REPRODUCTIVE AGE BREAST CANCER PATIENTS

To identify barriers to fertility preservation (FP) in newly diagnosed breast cancer patients who answered yes to the screening question “Have you ever had a desire to become a parent” and to compare demographic characteristics between patients who received and did not receive FP counseling.

Longitudinal study of AMH variations in 122 Adolescents and Young Adults (AYA) and non-AYA lymphoma patients to evaluate the chemo-induced ovarian toxicity to further personalise fertility preservation counselling.

What is the influence of age and chemotherapy regimen on the longitudinal blood anti-Müllerian hormone (AMH) variations in a large series of adolescents and young adult (AYA) (15-24 years old) and non-AYA (25-35 years old) lymphoma patients? In case of alkylating regimen treatment, there was a deep and sustained follicular depletion in AYA as well as non-AYA patients; however in both groups, the ovarian toxicity was extremely low in cases of non-alkylating treatments. AMH is now well-recognised to be a real-time indicator of ovarian follicular depletion and recovery in women treated by chemotherapy. Its longitudinal variations may discriminate between highly and minimally toxic protocols regarding ovarian function. It has been shown, in different cancer types, that age, type of chemotherapy regimen and pre-treatment AMH levels are the main predictors of ovarian recovery. Large studies on longitudinal AMH variations under chemotherapy in lymphoma patients are few but can provide the opportunity to assess the degree of follicle loss at a young age. This prospective cohort study was conducted in the Fertility Observatory of the Lille University Hospital. Data were collected between 2007 and 2016. Non-Hodgkin or Hodgkin lymphoma patients (n = 122) between 15 and 35 years old were prospectively recruited before commencing chemotherapy. Patients were treated either by a non-alkylating protocol (ABVD group; n = 67) or by an alkylating regimen (alkylating group; n = 55). Serial AMH measurements were performed at baseline (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 9, 12, 18 and 24 months from the end of chemotherapy. The whole study population was divided into two groups according to age: AYA (15-24; n = 65) and non-AYA (25-35; n = 57). All patients received a once monthly GnRH agonist injection during the whole treatment period. A linear mixed model was used to account for the repeated measures of single patients. At baseline, non-AYA patients had higher BMI and lower AMH levels than AYA patients. All AYA and non-AYA patients having received ABVD protocols had regular cycles at 12 months of follow-up. In case of alkylating regimens, amenorrhoea was more frequent in non-AYA patients than in AYA patients at 12 months (37% vs 4%, P = 0.011) and at 24 months (24% vs 4%, P = 0.045). We distinguished a similar depletion phase from AMH0 to AMH2 between ABVD and alkylating groups but significantly different recovery phases from AMH2 to AMH + 24 months. AMH recovery was fast and complete in case of ABVD protocols whatever the age: AMH reached pre-treatment values as soon as the 6th month of follow-up in the AYA group (mean (95% CI) in log AMH M0 vs M6: 3.07 (2.86 to 3.27) vs 3.05 (2.78 to 3.31), P = 1.00) and in the non-AYA group (mean (95% CI) in log AMH M0 vs M6: 2.73 (2.40 to 3.05) vs 2.47 (2.21 to 2.74), P = 1.00). In contrast, no patients from the alkylating group returned to pre-treatment AMH values whatever the age of patients (AYA or non-AYA). Moreover, none of the AMH values post-chemotherapy in the non-AYA group were significantly different from AMH2. Conversely in the AYA group, AMH levels from 6 months (mean (95% CI) in log AMH: 1.79 (1.47 to 2.11), P < 0.001) to 24 months (mean (95% CI) in log AMH: 2.16 (1.80 to 2.52), P ≤ 0.001) were significantly higher than AMH2 (mean (95% CI) in log AMH: 1.13 (0.89 to 1.38)). Considering the whole study population (AYA and non-AYA), pre-treatment AMH levels influenced the pattern of the AMH variation both in alkylating and ABVD protocols (interaction P-value = 0.005 and 0.043, respectively). Likewise, age was significantly associated with the pattern of the recovery phase but only in the alkylating group (interaction P-value =0.001). BMI had no influence on the AMH recovery phase whatever the protocol (interaction P-value = 0.98 in alkylating group, 0.72 in ABVD group). There was a large disparity in subtypes of protocols in the alkylating group. The average duration of chemotherapy for patients treated with alkylating protocols was longer than that for patients treated with ABVD. These results make it possible to develop strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients. In addition, it was confirmed that young age does not protect against ovarian damage caused by alkylating agents. This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (n° DOS/SDES/AR/FIR/2019/282). There are no competing interests. DC-2008-642 and CNIL DEC2015-112.

The fertility preservation decision-making and testicular sperm retrieval outcome in older adolescents with nonmosaic Klinefelter syndrome and azoospermia.

This study aims to analyze the fertility preservation decision-making and the sperm retrieval rate (SRR) in older adolescents (age 15-19 years) with nonmosaic Klinefelter syndrome (KS) and azoospermia in a male reproductive clinic, and to determine the accumulated SRR in older adolescents by literature review. Older adolescents with nonmosaic KS and azoospermia referred for hypogonadism and fertility concerns were enrolled. Reproductive counseling and fertility preservation options were offered to patients/parents. The acceptability and the reasons affecting the reproductive decision-making were analyzed. Patients/parents who agreed on fertility preservation received microdissection testicular sperm extraction (mTESE) and cryopreservation. A comprehensive literature review regarding the SRRs in older adolescents with KS was conducted. A total of eight older adolescents were enrolled. After fertility preservation counseling, three patients/parents (37.5%) agreed to receive mTESE, and spermatozoa were successfully retrieved in two. "Lack of interest" and "inconsistent sperm retrieval result" were the main reasons for refusal. A total of 89 older adolescents from nine articles, and ours were collected for SRR analysis. Most of the reports had a limited number of cases, and none of them described the acceptance rate of sperm retrieval in adolescents. Forty-three out of 89 older adolescents (48.3%) had successful sperm retrieval, and there was no significant difference in the SRR between the mTESE and conventional TESE. Successful testicular sperm retrieval in older adolescents with KS is not superior to those reported in adults. Adolescents and their parents should undergo a detailed reproductive consultation process and shared decision-making discussion before considering testicular sperm retrieval.

P–432 Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

Abstract Study question Do stage and grade of breast cancer impact the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation? Summary answer Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. Higher grade breast cancer requires higher gonadotropin doses during stimulation. What is known already Cancer can impair ovarian response by unknown mechanisms. Some authors suggest that it could be detrimental on fertility because it elicits a catabolic state, increasing stress hormone levels. Some studies have also shown that ovarian response to controlled ovarian stimulation (COS) is, in some way, compromised in oncological patients. Little is known about the impact of different types of cancer on ovarian reserve, and specifically whether higher stage and grade could compromise egg retrieval during fertility preservation (FP) techniques. Study design, size, duration: Retrospective cohort study evaluating data of FP treatment cycles among women with breast cancer at the Oncofertility Unit of San Raffaele Hospital, Milan in the period from 2011 to 2019. Participants/materials, setting, methods Inclusion criteria were: breast cancer diagnosis; age 22–41; oocyte cryopreservation after stimulation with a random start GnRH-antagonist protocol. Patients receiving chemotherapy before FP were excluded. We compared outcomes between low-stage (stage I) and high-stage (stage II-III) patients and low-grade (G1-G2) and high-grade (G3) patients. Main study outcome was the total number of retrieved mature oocytes. Univariate analysis was performed by Mann-Whitney test, Kruskal-Wallis test and Fisher’s exact test. Multivariate analysis was performed by logistic regression. Main results and the role of chance 101 stimulation cycles were included. High-stage disease patients were significantly younger than low-stage. Median antral follicle count (AFC) was 12 in low-stage and 10 in high-stage (age-adjusted p = 0.92) and median anti-mullerian hormone (AMH) levels were 1.9 ug/L in low-stage and 1.8 ug/L in high-stage (age-adjusted p = 0.22). No significant difference in stimulation protocols and follicle-stimulating hormone (FSH) start and total dose could be detected between the 2 groups. Median number of vitrified oocytes was 7 in both groups (p = 0.75). No significant difference could be observed in median AFC (13 vs 10, p = 0.14) and AMH levels (2.1 vs 1.5, p = 0.88) between low-grade and high-grade disease patients. When adjusting for age, AFC was found to be significantly lower in high-grade disease patients (p = 0.03). Patients with high-grade tumors were stimulated with higher doses of FSH (age-adjusted p-value=0.03). Median number of vitrified oocytes was 6 in low-grade patients and 7 in high-grade (p = 0.35). In a multivariate model including age, cancer stage, cancer grade and molecular classification, the only significant factor found to be inversely associated with AFC was cancer grade (OR 3.6; 95% CI 0.7 – 6.5, p = 0.01), while only age was significantly associated with oocyte retrieval (OR 0.4; 95% CI 0.01 – 0.9, p = 0.04). Limitations, reasons for caution The main limitations of our study are its retrospective design and the small sample size. Wider implications of the findings: Fertility preservation counselling and ovarian stimulation protocols of breast cancer patients could be implemented with cancer grade. Trial registration number Not applicable

P–462 First live birth after fertility preservation using vitrified oocytes in a woman with mosaic Turner syndrome

Abstract Study question Is oocyte vitrification an option for preserving the fertility of women diagnosed with Turner syndrome (TS)? Summary answer We report the first live birth achieved using cryopreserved oocytes in a woman diagnosed with mosaic Turner syndrome. What is known already Women with TS are at extremely high risk for premature ovarian insufficiency (POI) and infertility. Although the desire of becoming parents may be fulfilled through egg donation or adoption, fertility preservation using ovarian tissue cryopreservation or oocyte vitrification has been offered to adolescents with TS before complete exhaustion of their follicular stockpile. However, women with TS exhibit higher rates of pregnancy loss and obstetric complications, and the feasibility of fertility preservation in TS is hampered by the reduced follicular pool and by concerns about the X chromosomal content of oocytes and follicular cells. Study design, size, duration Case report in a university hospital. Participants/materials, setting, methods A 25-year-old woman with Turner syndrome mosaicism (45,X0[14]/46,XX[86]) was referred for fertility preservation (FP) counseling. Serum antimüllerian hormone (AMH) level was normal (6.4 µg/L). In view of parenthood postponement and because of the unpredictable rate of follicle loss, the woman underwent two cycles of ovarian stimulation using recombinant follicle stimulating hormone (rFSH), 200–250 IU/day for 8 resp. 12 days, in a GnRH antagonist protocol. Main results and the role of chance In total, 29 metaphase II oocytes (MII) were vitrified. Five years later, the patient returned to the clinic with a desire for pregnancy. Because of evidence of considerable AMH decline (–56% in an interval of four years), the patient was advised to utilize her cryopreserved oocytes for in-vitro fertilization with preimplantation genetic testing for aneuploidy screening (PGT-A). All 29 MII oocytes were thawed; 26 oocytes survived (89.7%) and were inseminated using intracytoplasmic sperm injection (ICSI). Thirteen oocytes were fertilized normally. Three good quality blastocysts ensued and were vitrified after trophectoderm biopsy for PGT-A using array-CGH. Two blastocysts were found euploid. One was thawed and transferred into the uterus using a HRT priming protocol. An uneventful pregnancy occurred. The patient delivered a healthy baby girl weighing 3490 g at 40 weeks of gestation. Limitations, reasons for caution Cryopreservation of oocytes and/or ovarian tissue in selected postmenarchal girls or young women with Turner syndrome is an investigational FP approach that may result in genetic parenthood. The feasibility of FP in TS individuals is limited to those with evidence of ovarian function, before POI occurs. Wider implications of the findings: Cryopreservation of mature oocytes after ovarian stimulation is a realistic option for FP in selected postmenarchal individuals with mosaic TS. Whether PGT-A may reduce the risk of pregnancy loss in TS has to be confirmed by further studies. Trial registration number Not applicable

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH &amp;gt; 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

Perceptions of Oncology Nurses Regarding Fertility Preservation and Providing Oncofertility Services for Men of Childbearing Age with Cancer.

This study investigated the knowledge, thoughts, and attitudes of oncology nurses in China regarding fertility preservation for male cancer patients of childbearing age, and for offering counseling or oncofertility services for the men in their care. Data was collected from 18 oncology nurses in Southwest China through voluntary self-report and in-depth interviews. The qualitative interview data were analyzed using a descriptive phenomenology method based on the lived experience of the nurses. The interviewees commonly reported 6 main concerns regarding fertility preservation (FP): their insufficient knowledge and inadequate nursing education; the importance of offering such services to cancer patients; legal vulnerability if FP information is withheld from patients; the role of the nurse in counseling; and barriers to discussing FP in practice. Nurses had a positive attitude toward FP, but most had no practical role in routinely informing male patients of their options, and the nurses believed that discussion of FP was outside their scope of practice. This study offers insight into the perceptions of oncology nurses in a developing country regarding the provision of FP services for adult male cancer patients. These results lead us to recommend that local fertility nurses should be given new training regarding FP. Furthermore, nurse-led clinics are desirable. Future research should focus on the effectiveness of nurse participation in FP counseling and referral, and how to improve the professional confidence of oncology nurses for addressing FP issues.

Reproductive potential and fertility preservation in transgender and nonbinary individuals.

To synthesize recent literature to better understand parenting desires and challenges of transgender individuals as well as the impact of gender-affirming care on reproductive potential. Survey studies of transgender and nonbinary individuals demonstrate significant parenting interest, yet uptake in fertility preservation services remains low with potential for decisional regret. Masculinizing hormones have demonstrated variable effects on folliculogenesis and follicle distribution in the human ovary. In the mouse model, testosterone administration has demonstrated an increase in atretic late antral follicles without a reduction in primordial or total antral follicle counts and a preserved ability to respond to gonadotropin stimulation. Case series of transgender individuals undergoing oocyte or embryo cryopreservation are promising with outcomes similar to cisgender controls. Feminizing hormones have shown detrimental effects on sperm parameters at time of cryopreservation and spermatogenesis in orchiectomy samples with uncertainty regarding the reversibility of these changes. Current evidence demonstrates variable effects of gender-affirming hormones on ovarian and testicular function with potential for detrimental impact on an individual's reproductive potential. As many individuals initiate gender-affirming care prior to or during their reproductive years it is imperative that they receive thorough fertility preservation counseling and improved access to reproductive care services.

A survey study of knowledge, attitude, and practice regarding oncofertility among health professionals in Uruguay.

e24041 Background: Oncofertility is a field dedicated to preserve fertility of children, adolescents, and young cancer patients'. For young cancer patients, fertility preservation (FP) has become an important concern that needs to be addressed before cancer treatment. This study aimed to evaluate the general knowledge, attitudes, and practice towards FP and pregnancy-related issues of health care professionals in Uruguay. Methods: We conducted an online survey distributed to physicians from multidisciplinary areas (Oncology, Radiotherapy, Hematology, Pediatric hematology-oncology, Gynecology, Urology) involved in daily medical care to young cancer patients. Results: 208 physicians from 16 geographical regions completed the survey. 53 % of the subjects were less than 40 years old, and 77.7% identified themselves as women. Most of the responders (99 %) agreed that FP counseling should be part of cancer treatment; however, only 49 % discusses FP and refers their patients in their daily clinical practice. Regarding referral of patients to an Oncofertility specialist, 36% do it occasionally, and 15% have never referred. Half of the responders (50%) stated that they know the available FP options for young cancer patients, 49% have an idea, and 1% are not aware. 37 % of participants consider that FP treatments would delay cancer treatment initiation, impacting their attitude towards FP recommendation and referral. Regarding FP coverage, 51.7 % were not aware of financial coverage for fertility preservation treatments availableness. 57% of physicians directly involved in breast cancer (BC) care agreed with the statement that oocyte cryopreservation is safe in BC patients with positive hormonal receptors, 35% are not sure, and 8% believe it is not safe, 46% believe pregnancy is safe after BC, 34% is not sure, while 20% consider it is unsafe. Conclusions: This study demonstrates the need to increase FP awareness in Uruguayan health care professionals. Moreover, several misconceptions on FP and pregnancy-related issues in BC patients have been identified. Focused research and education to improve physicians' knowledge and adherence to available international guidelines are urgently required to improve the care of young cancer patients who desire future fertility. Key Words: Oncofertility, fertility preservation, oocyte cryopreservation, breast cancer, pregnancy.

Chemotherapy-based gonadotoxicity risk evaluation as a predictor of reproductive outcomes in post-pubertal patients following ovarian tissue cryopreservation

BackgroundThe sterilizing effect of cancer treatment depends mostly on the chemotherapy regimen and extent of radiotherapy. Prediction of long-term reproductive outcomes among cancer survivors according to chemo-radiotherapy regimen may improve pre-treatment fertility preservation counseling and future reproductive outcomes.MethodsThe aim of this study was to evaluate long term reproductive outcomes in cancer survivors according to gonadotoxicity risk estimation of the chemo-radiotherapy regimens utilized. This retrospective cohort study was comprised of post-pubertal female patients referred for fertility preservation during 1997 and 2017 was performed. Eligible adult patients were addressed and asked to complete a clinical survey regarding their ovarian function, menstruation, reproductive experience and ovarian tissue auto-transplantation procedures. Results were stratified according to the gonadotoxic potential of chemotherapy and radiotherapy they received—low, moderate and high-risk, defined by the regimen used, the cumulative dose of chemotherapy administered and radiation therapy extent.ResultsA total of 120 patients were eligible for the survey. Of those, 92 patients agreed to answer the questionnaire. Data regarding chemotherapy regimen were available for 77 of the 92 patients who answered the questionnaire. Menopause symptoms were much more prevalent in patients undergoing high vs moderate and low-risk chemotherapy protocol. (51.4% vs. 27.3% and 16.7%, respectively; p < 0.05). Spontaneous pregnancy rates were also significantly lower in the high-risk compared with the low-risk gonadotoxicity regimen group (32.0% vs. 58.3% and 87.5%, respectively; p < 0.05).ConclusionPatients scheduled for aggressive cancer treatment have significantly higher rates of menopause symptoms and more than double the risk of struggling to conceive spontaneously. Improving prediction of future reproductive outcomes according to treatment protocol and counseling in early stages of cancer diagnosis and treatment may contribute to a tailored fertility related consultation among cancer survivors.

Pediatric and Adolescent Oncofertility in Male Patients-From Alpha to Omega.

This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and adolescents aged 0–19 years will be diagnosed with cancer each year. Fertility is compromised in one-third of adult male survivors of childhood cancer. We present the latest approaches and techniques for fertility preservation, starting with fertility preservation counselling, a clinical practice guideline used around the world and finishing with recent advances in basic science and translational research. Improving strategies for the maturation of germ cells in vitro combined with new molecular techniques for gene editing could be the next scientific keystone to eradicate genetic diseases such as cancer related mutations in the offspring of cancer survivors.

89. Bridging the Gap - Creating A National Fertility Preservation and Reproductive Late Effects Database to Improve Outcomes

<h3>Background</h3> Cancer five-year survival rates have improved to 85% for pediatric, adolescent and young adults, creating opportunities to optimize long-term health and quality of life (QoL) in survivorship1. Infertility and adverse reproductive health outcomes significantly alter QoL and affect 12-88% of at-risk survivors2-6. National guidelines recommend fertility preservation (FP) counseling prior to cancer therapies in reproductive age survivors. However, implementation of guidelines remains a challenge and reproductive late effects (LE) beyond infertility remain under addressed. To bridge this gap, we describe the early stages of development of a national database designed to create a framework for data sharing to facilitate research and improve fertility and reproductive health outcomes. <h3>Methods</h3> A multidisciplinary team of FP experts, biostatisticians, and informaticists examined three existing databases to define a standard set of variables to incorporate into a pilot database. The pilot sites include Children's Hospital Colorado and University of Colorado Hospital and will expand to additional sites within the Oncofertility Consortium. The population includes males and females ages 1 month to 39 years with medical conditions and/or treatments associated with fertility impairment. In addition, we assessed a subset of variables (age, diagnosis and attempted FP) to determine feasibility. <h3>Results</h3> We created a well-defined data dictionary after evaluating existing and potential new variables. We included common variables such as cancer treatments and fertility assessments and expanded to include reproductive LE. The latter includes radiation-induced uterine/vaginal injury, genital graft-versus-host disease, hypogonadism, and sexual dysfunction. To illustrate feasibility, we identified 126 patients at the pilot sites from January 2020 to September 2020. Of those, 48% were females ages 6-38 (median 21) and 52% were males ages 1-39 (median 19) years. Leukemia (18%), sarcoma (14%), lymphoma (11%), and breast (11%) were the most common diagnoses. Fourteen patients received gonadotoxic therapies for non-malignant conditions. FP was pursued in 32% of females and 84% of males. Results for reproductive LE variables are being quantified. <h3>Conclusions</h3> A standardized clinical outcomes database that is utilized by a growing network of FP and reproductive health programs will help strengthen research through data sharing and expedite implementation of clinical guidelines. Future steps are to (1) scale to additional sites, (2) refine and prioritize variables to reflect practices across centers, (3) automate data import, and (4) refine the process of initiating hypothesis-driven research across centers.

Fertility Preservation Counseling for Women With Gynecological Cancer

Fertility Preservation Counseling for Women With Gynecological Cancer

The challenge of defining predictive parameters for fertility preservation counseling in young females with Turner syndrome

Sir, Recently, a review by Nawroth et al and an accompanying editorial on fertility preservation (FP) counseling in females with Turner syndrome (TS) by Rodriguez-Wallberg and Landin-Wilhelmsen were published.1, 2 We agree with the authors of both articles that FP counseling in TS patients is challenging because the decision to perform FP depends on multiple factors and not just on the ovarian reserve. Nawroth et al present in their review a flowchart to summarize their recommendations, which in our opinion is far too simplistic. This has been partially covered in the editorial.2 However, we would like to address several additional points that require further attention. First, the flowchart indicates that cardiologic screening should only be provided to monosomic TS patients. We agree with the opinion expressed in the editorial that cardiologic screening should be provided to all TS patients, in accordance with the Swedish guidelines for management of women and girls with TS.2 In line with the Cincinnati clinical practice guideline of TS patients, each girl in the Netherlands diagnosed with TS will have a diagnostic work-up phase, including cardiologic screening, which is similar to the Health Care Program in Sweden. Although it is reported that mosaic TS patients have a lower risk of cardiovascular and obstetric complications compared with other TS patients, cardiovascular complications can occur in all women with TS.3 Therefore, the karyotype of TS patients cannot be used as a predictive marker for cardiovascular risk evaluation. Secondly, the flowchart of Nawroth et al divides TS in two groups based on karyotypical aberrations. Peek et al have recently shown that the level of mosaicism in extra-ovarian cells was not predictive of the level of mosaicism in ovarian cells in the same patient.4 These findings have been substantiated by a case report of a girl who was initially diagnosed with 45,X, whereas a cryptic mosaicism was present in the ovary.5 Therefore, it is difficult to assign TS patients to a particular group, as cryptic cell lines may be present in the ovary that are likely to determine its reproductive potential. In our opinion, an international standard should be developed, describing which peripheral cells and number of cells should be karyotyped in order to assign a TS patient to a specific group. Thirdly, Nawroth et al gave anti-Müllerian hormone (AMH) a central position in their flowchart despite their statement that the prognostic value of AMH in determining the ovarian reserve in young TS patients is limited. Hagen et al reported that AMH levels correlated significantly with ovarian function in a relatively small group of TS patients aged 12-25 years and stated that this marker might be used for this group during FP counseling.6 However, the flowchart also presents AMH as a prognostic marker for prepubertal children, whereas it remains unclear what the prognostic value of AMH is in this group. Furthermore, AMH levels measured at different time points can vary considerably in the same patient, due to biological variability and inter-test variability of AMH assays. Therefore, adequate interpretation of AMH levels in this group is difficult. FP counseling in young TS patients is challenging and reliable predictive parameters are required to optimize this process. AMH should be interpreted with caution, due to its known limitations.

Theory-Guided Development of Fertility Care Implementation Strategies for Adolescent and Young Adult Cancer Survivors.

Purpose: Oncofertility care at cancer diagnosis remains underimplemented across oncology and fertility care settings, with limited tools to scale up effective implementation strategies. Using implementation science theory, we systematically assessed factors that influence oncofertility care implementation and mapped scalable strategies, particularly electronic health record (EHR)-enabled ones, that fit adult and pediatric oncology care contexts. Methods: Using purposeful sampling, we recruited health care providers and female, reproductive-aged survivors of adolescent and young adult (AYA) cancers (AYA survivors) from a comprehensive cancer center and a freestanding children's hospital to semistructured interviews and focus groups. Using thematic analysis combining inductive codes with deductive codes using the Consolidated Framework for Implementation Research (CFIR), we characterized barriers and facilitators to care and designed responsive strategies. Two coders independently coded each transcript. Results: We recruited 19 oncology and fertility providers and 9 cancer survivors. We identified barriers and facilitators to oncofertility care in the CFIR domains of individual, inner setting, outer setting, and process, allowing us to conceptualize oncofertility care to encompass three core components (screening, referral, and fertility preservation counseling) and map five strategies to these components that fit an adult and a children's context and bridge oncology and fertility practices. The strategies were screening using a best practice advisory, referral order, telehealth fertility counseling, provider audit and feedback, and provider education. All but provider education were EHR tools with embedded efficiencies. Conclusion: An implementation science approach systematically assessed oncofertility care and mapped strategies to provide a theory-based approach and scalable EHR tools to support wider dissemination.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.