Fertility preservation and fertility treatment use in young breast cancer survivors reporting a live birth.

Purpose: Several international organizations and guidelines have recommended implementation of structured fertility preservation (FP) discussions with patients and their families before initiation of chemotherapy and radiation treatments in children. This study aimed to identify current trends and rates in FP counseling and treatments at a Canadian pediatric tertiary care center. Objectives were to measure guideline adherence for FP counseling at our institution by determining (1) the frequency of FP counseling in pediatric female oncological patients at our institution, (2) the frequency of FP treatment in this study population, and (3) the factors associated with FP pre-treatment counseling. Methods: A retrospective chart review was performed, including all pediatric and adolescent female patients (age <18) seen in consultation by the oncology team. Demographic data, as well as documentation of FP counseling and referral to a reproductive endocrinology and infertility (REI) specialist and subsequent FP treatment were collected. Results: A total of 89 female pediatric patients were included in our study. Forty-two patients received fertility counseling (47.2%; 95% confidence interval [CI] 37.2-57.5). Only 29/42 (69.0%; 95% CI: 54-80.9) received counseling before onset of treatment. A 12/42 (41.4%; 95% CI: 25-59.3) of the patients who received FP counseling were referred to an REI specialist and 11/12 proceeded with FP treatment (37.9%, 95% CI: 22.7-56). Conclusion: This study presents contemporary data on the rates of FP counseling in Canadian pediatric female oncological patients and demonstrates low rates of FP counseling in our patient population.

STUDY QUESTIONIn a transgender population referred for fertility consultation, which factors influence the decision to cryopreserve oocytes and sperm?SUMMARY ANSWERPrevious hormonal treatment, gender affirmation surgery and sexual orientation were associated with the decision to undergo fertility preservation and transgender women underwent fertility preservation more frequently than transgender men.WHAT IS KNOWN ALREADYIt is well-known internationally that fertility preservation and fertility treatment are increasingly requested by transgender men and women. Factors affecting their decisions as well as treatment differences between transgender women and transgender men have been reported, but many studies have had low participation rates and small sample sizes.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study, conducted during 2013–2018, included 78 transgender women (assigned male at birth and referred for sperm cryopreservation) and 164 transgender men (assigned female at birth referred for oocyte cryopreservation).PARTICIPANTS/MATERIALS, SETTING, METHODSIn 2013, the previous requirement for sterilization before completion of a legal gender change was removed in Sweden. All fertile-aged transgender men and transgender women referred to a tertiary care centre for consultation concerning fertility preservation, fertility treatment or hysterectomy were identified from administrative systems. Demographic, medical and treatment data were extracted from electronic medical records and from an ART database. Logistic regression was applied to analyse factors affecting the decision to cryopreserve gametes among transgender men and transgender women.MAIN RESULTS AND THE ROLE OF CHANCEA majority of transgender men (69.5%) and transgender women (82%), wanted to become parents. Fertility preservation was less frequent in transgender men than in transgender women (26.2% versus 75.6%, respectively). No individuals among those primarily referred for hysterectomy opted for cryopreservation of oocytes. Among transgender men, young age, no previous hormonal treatment and stating homosexual orientation were independent factors associated with the decision to cryopreserve oocytes. Among transgender women, the decision to undergo gender affirmation surgery and stating heterosexual orientation were independent factors associated with a decision to refrain from fertility preservation. Fertility treatments, using IUI or IVF with donor sperm, were mainly performed in partners of transgender men. Ten live births were reported in the group of transgender men and two for transgender women.LIMITATIONS, REASONS FOR CAUTIONThe main limitation is the retrospective nature of the study, with missing data for many variables. The short study period and the study population being too young to permit observation of long-term outcomes of fertility preservation and fertility treatments are reasons for caution.WIDER IMPLICATIONS OF THE FINDINGSOur results confirm that fertility preservation has been requested by transgender people since the change in Swedish legislation in 2013. Information about aspects of fertility early in the transition process is important, since hormonal and surgical treatments may have a large impact on the decision to undergo fertility preservation. It is important to train fertility clinic staff to identify and handle the specific obstacles, as well as address the need for information and support that transgender people may have when planning for fertility preservation, fertility treatment and pregnancy.STUDY FUNDING/COMPETING INTEREST(S)This research was supported by a grant from the Swedish state, under the ALF agreement between the Swedish government and the county councils (ALFGBG-720291), and by Hjalmar Svensson’s Research Foundation. None of the authors has any conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.

Fertility is a top concern for many survivors of cancer diagnosed as children, adolescents and young adults (CAYA). Fertility preservation (FP) treatments are effective, evidence-based interventions to support their family building goals. Fertility discussions are a part of quality oncology care throughout the cancer care continuum. For nearly 2 decades, clinical guidelines recommend counseling patients about the possibility of infertility promptly at diagnosis and offering FP options and referrals as indicated. Multiple guidelines now recommend post-treatment counseling. Infertility risks differ by cancer treatments and age, rendering risk stratification a central part of FP care. To support FP decision-making, online tools for female risk estimation are available. At diagnosis, females can engage in mature oocyte/embryo cryopreservation, ovarian tissue cryopreservation, ovarian suppression with GnRH agonists, in vitro oocyte maturation, and/or conservative management for gynecologic cancers. Post-treatment, several populations may consider undergoing oocyte/embryo cryopreservation. Male survivors' standard of care FP treatments center on sperm cryopreservation before cancer treatment and do not have the same post-treatment indication for additional gamete cryopreservation. In practice, FP care requires systemized processes to routinely screen for FP needs, bridge oncology referrals to fertility, offer timely fertility consultations and access to FP treatments, and support financial navigation. Sixteen US states passed laws requiring health insurers to provide insurance benefits for FP treatments, but variation among the laws and downstream implementation are barriers to accessing FP treatments. To preserve the reproductive futures of CAYA survivors, research is needed to improve risk stratification, FP options, and delivery of FP care.

Background: More than 12,000 new diagnoses of breast cancer occur annually in women &amp;lt;40 years old and most will become survivors. It is recommended that young women with breast cancer be counseled about fertility preservation (FP) options prior to initiation of systemic therapy if they are interested in having biologic children in the future. Decisions to pursue FP are multifactorial and current data suggest only a small proportion of women pursue FP before breast cancer treatment. This study examines the decisions and outcomes of women who pursue FP before treatment and family building after therapy. Methods: An IRB approved web-based cross-sectional survey examining decisions about FP, factors influencing decisions, and post-decision regret was administered to young (age 18-45) breast cancer survivors with stage I-III breast cancer who were either English or Spanish speaking. All women received counseling by a MSK Fertility Nurse Specialist prior to initiating cancer treatment at MSKCC in 2009-2017. Clinical data was also extracted from the medical record .Results: Our sample consisted of 211 women with a mean and median age of 34 (age range was 20-45) and 82% had ER+ disease, 19% had HER-2+ disease and 12% had triple negative breast cancer. At the time of diagnosis, 46 women (22%) had children and 173 women (61%) were married or living with a partner. 151 (72%) of study participants wanted to have (more) children, 48 (23%) were unsure and 12 (6%) did not want additional children. Prior to treatment, 172 (82%) women met with a reproductive endocrinologist (RE), and 122 (58%) underwent FP: 73 froze eggs and 49 froze embryos. After treatment, 28 (13%) women met with a RE, and 13 underwent FP: 9 froze eggs and 4 froze embryos. 26 (12%) patients opted to just use a GnRH agonist during chemotherapy. For women who froze eggs, the average number obtained was 14 pre-treatment and 18 post-treatment. Of those who froze embryos, the average number obtained was 7 both pre- and post-treatment. Concern with financial burden was noted in 58% of women. Insurance did not cover any FP treatment for 56/122 (46%) of women. 32% (39/122) of women paid $10,000 or more for their FP. Women reported that the most important factor that contributed to their FP decision was the ability to feel hopeful about their future followed by concern that they would have regrets if they did not undergo FP. Additional factors that contributed to the FP decision were the desire to have biologic children, feeling overwhelmed by the cancer diagnosis, the cost of freezing eggs or embryos and concern about taking hormone medication. Reflecting back 176 women (83%) believe they made the right decision regarding FP. After completing primary breast cancer treatment, 61 women (29%) opted to try to build their family and 42 had children: 35 gave birth and 7 used a surrogate. Currently 3 women are pregnant, and 10 are pursuing pregnancy. 19 (31%) women conceived without fertility treatment and 22 (36%) women used or are currently pursuing assisted reproduction. 1 woman used a donor egg and 15 successfully used frozen eggs/embryos harvested prior to treatment. Delay of endocrine therapy to pursue pregnancy was uncommon, reported by only 6 women. However, 23 women interrupted endocrine therapy to conceive. Conclusions: The majority of women who attempted family building after treatment were able to have children. Many of these women used eggs/embryos frozen before breast cancer treatment either by getting pregnant themselves or via surrogacy. These data stress the importance of early discussion with a fertility nurse specialist regarding risks and preservation options followed by prompt referral to a reproductive endocrinologist. In addition, FP helped women to feel hopeful about their future and the majority of women believe they made the right decision. Citation Format: Shari B Goldfarb, Bridgette Thom, Cassandra Chang, Nadia Abdo, Andrea Carpio, Rosemary Semler, Catherine Benedict, Patricia Hershberger, Joanne F Kelvin, Mary L Gemignani. Decisions and outcomes of young women with breast cancer regarding fertility preservation before cancer treatment and family building after treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-03.

Insurance companies generally cover treatment for iatrogenic conditions that result from cancer treatment, including treatment for conditions that may be considered elective when “naturally” occurring (note that in this article, I am using the word “iatrogenic” to refer only to nonnegligent treatment-induced conditions). One notable exception is fertility preservation for iatrogenic infertility. In this brief article, I argue that for insurance companies to maintain consistency, they should cover fertility preservation treatment for female patients with cancer because it does not differ significantly from other treatments for iatrogenic conditions they currently cover for women, such as breast reconstruction after mastectomy and wigs for alopecia. (Although my focus in this article in on female fertility preservation, one could presumably make a similar argument that male fertility preservation should be covered by insurance.) One reason many insurance companies refuse to cover fertility preservation treatments, and infertility treatments more generally, is that they are often viewed as elective procedures, not medically necessary ones. When it comes to iatrogenic infertility, however, the controversy over whether fertility preservation is a medically necessary treatment should be moot because other so-called elective procedures are covered when they are iatrogenic, even if they are not covered when naturally occurring. Because my focus is on iatrogenic conditions—many of which, as I will discuss in this article, are generally not considered medical conditions when they are not iatrogenic—I put aside the debate about whether infertility should be classified as a “real” disease. One example of an iatrogenic condition typically covered by insurance is breast reconstruction after lumpectomy or mastectomy. Although having only one breast is rarely, and perhaps never, a naturally occurring condition, naturally occurring breast asymmetry is quite common. Most would not classify breast asymmetry as a medical problem that insurance should cover. However, when breast asymmetry results from a lumpectomy, surgery to achieve symmetry is usually covered regardless of whether the patient had symmetric breasts beforehand. This discrepancy in coverage between iatrogenic and naturally occurring breast asymmetry can be explained, at least in part, by looking at the harm principle through the lens of responsibility: because members of the medical profession caused the harm—something they are not supposed to do—the medical profession as a whole must take responsibility for mitigating the harm. (Another factor is the static understanding of the body that dominates medicine and science. Briefly, this is the idea that the body stays the same over time and disease is aberration that must be eradicated to restore the body to its natural and “normal” state. See Eckenwiler for a discussion of how this static understanding of the body has lead to women’s exclusion from clinical research trials.) Certain acts and laws were passed to institutionalize the medical realm’s responsibility for iatrogenic harms. For instance, the Women’s Health and Cancer Rights Act, which was passed in 1998, mandates that if health insurance companies cover the costs of mastectomy for cancer patients, then they must also cover the costs of breast reconstruction for mastectomy patients. Health care providers and insurance companies sometimes assume responsibility for iatrogenic harms by the way they code for billing. For example, breast reconstruction surgery after a mastectomy is coded as cancer treatment rather than under elective treatment. By allowing treatments for iatrogenic conditions to be subsumed into the larger category of disease treatment, insurance companies are tacitly accepting financial responsibility to cover these treatments. In addition to breast reconstruction surgery, there are other treatments that may not be covered by insurance when the disease is naturally occurring (in part because treatment is not seen as medically necessary), but are covered when iatrogenic; for example, wigs after cancer treatment are usually covered, whereas wigs for thinning hair or cosmetic reasons often are not. The same pattern of insurance coverage exists in the fertility/ infertility realm. Many insurance companies do not cover infertility or fertility preservation treatments for some of the following reasons: in/fertility treatments are experimental, they do not treat an underlying disease but rather produce a desired outcome (ie, a child), and they are an elective procedure, not a medical one. An exception to the lack of coverage is iatrogenic infertility. Although no formal studies have been done, there is anecdotal evidence that insurance companies will sometimes take financial responsibility for iatrogenic infertility. At the Northwestern University branch of the Oncofertility Consortium (www.oncofertility.northwestern.edu), a national, interdisciplinary initiative designed to explore the reproductive options for patients diagnosed with cancer or other serious diseases, female patients with cancer have the option to chose a fertility preservation method— embryo, egg, or ovarian tissue cryopreservation—before beginning cancer treatment. These fertility preservation treatments have been billed under a primary diagnosis of cancer and a secondary diagnosis JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 28 NUMBER 8 MARCH 1

9109 Background: Young women with cancer are referred to discuss fertility preservation (FP), but due to time pressure and complexity of FP treatments, their comprehension of FP may be poor. We conducted a multi-center study to evaluate factors associated with knowledge about fertility preservation (FP) treatment following FP consultation. Methods: A survey instrument was developed to assess a patient's understanding of FP options after FP consultation. Information was collected about demographics, support systems, decisional conflict and perceived risks. A pilot group evaluated the survey and results were used to refine the content. The revised instrument was completed by consecutive new patients (ages 18-41) between 2008 and 2010, 3-12 months after initial FP consultation. Each correct answer was given one point to yield a knowledge score (KS) (maximum = 22). Results: Among 94 eligible subjects, 72 were successfully contacted and 51 completed the survey (71%). Median KS was 12 (range 4-19). Higher KS was noted in women who were college educated (12.4 vs. 9.2; p<0.01), Caucasian (12.3 vs. 10, p=0.03), had someone present at FP consultation (12.4 vs. 10.6, p=0.05), discussed FP options with someone (12.4 vs. 9.5, p<0.01), and used specific websites (eg FertileHope; 12.6 vs. 10.7, p=0.02). KS trended higher in subjects who discussed their FP options with their oncologist (p=0.06) and those who had contact with the FP provider following consultation (p=0.09). KS was not correlated with age, income, receiving FP treatment or decisional conflict. Conclusions: Post-consultation knowledge about FP options was poor, possibly due to stress and information complexity. Our data suggest that patients may have improved comprehension if they bring someone with them to the consultation, discuss options with someone after the visit, and reference specific FP websites. These actions may improve a patient's overall understanding about FP options.

Ovarian stimulation and fertility preservation with the use of aromatase inhibitors in women with breast cancer

Current studies show that about half of transgender and gender-diverse (TGD) people wish to have children in the future. TGD patients who pursue gender-affirmation interventions must be aware of the impact that various treatments can have on fertility, as gender-affirming care through medical or surgical treatment can limit or alter reproductive potential. Many medical professional societies encourage providers to educate and counsel patients about the consequences of treatment and viable options for fertility preservation (FP) as early as possible, though patients may not be aware of all the family formation methods available. There is a significant need for a tool that thoroughly details not only the various opportunities for parenthood but the perceived cost, rates of success, and risks associated with each option. A fertility decision-aid would allow for a more robust informed consent process and shared decision-making for all individuals pursuing gender-affirming care.

Purpose: Fertility preservation procedures aim at offering young cancer patients an opportunity to build their future families and have biologically-related children. Optimization of fertility preservation options is needed to maximize the chances to success, as the procedures are usually performed as an emergency and they cannot be repeated in most of the patients. We aimed at investigate the predictive value of serum concentrations of Anti-Mullerian Hormone (AMH) in the outcome of emergency controlled hormonal stimulation (COS) treatments aimed at fertility preservation in women with breast cancer. Patients and methods: Prospective cohort study. Patients with breast cancer of reproductive age were included in the study at time of counseling for emergency fertility preservation indicated by planned chemotherapy between January 2012 and May 2016. All fertility preservation treatments were performed at the Reproductive Medicine Clinic of Karolinska University Hospital. The study cohort included 124 women with breast cancer that underwent COS cycles using an antagonist protocol either with or without letrozole supplementation, depending on their tumor estrogen receptor status. Blood draws for estimation of serum AMH concentrations were sampled previously to breast cancer treatment initiation and immediately before performance of fertility preservation. Main Outcome measures: The main outcome was the association of baseline serum AMH concentration, crude and age-adjusted, with the number of obtained and cryopreserved oocytes or embryos during the subsequent fertility preservation treatment. Results Our preliminary analyses indicate that AMH levels estimated previously to a fertility preservation treatment in women with breast cancer might be a reliable predictor of the outcome of fertility preservation in some age subgroups. The association of AMH levels with fertility preservation outcomes did lack significance in the women that were youngest at time of breast cancer diagnosis, indicating that novel biomarkers are needed in this particular patient group to optimize their fertility preservation treatments. Additionally, women that were on oral contraceptives previously to their breast cancer diagnosis presented with unusually low AMH levels for their age, which also did not correspond to their response to fertility preservation. A logistic regression analysis of the outcome including the chosen variables will follow. Conclusion The predictive value of AMH concentration before COS in emergency fertility preservation for women with breast cancer is still debatable. Measurements of AMH concentrations to evaluate ovarian reserve previously to fertility preservation might not correlate with the outcome in all patients with breast cancer and novel biomarkers should be investigated. Citation Format: Rodriguez-Wallberg KA, Wikander I. Predictive value of serum anti-Mullerian hormone (AMH) in the outcome of emergency fertility preservation treatments indicated by breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-12-05.

COMPARISON OF DISPOSITION DECISIONS OF ELECTIVE FERTILITY PRESERVATION VERSUS FERTILITY TREATMENT PATIENT POPULATIONS UTILIZING ASSISTED REPRODUCTIVE TECHNOLOGIES

Study question What is the gonadotoxic potential of the EURONET-PHL-C2 treatment protocol for female childhood Hodgkin lymphoma patients, and how frequently are co-treatments to preserve fertility applied? Summary answer Treatment-induced amenorrhea (72%) persisted in &amp;gt; 10% of cases. Results on AMH are available by April 2023. Fertility preserving (co-)treatments were applied in 27% of patients. What is known already Current treatment for childhood Hodgkin lymphoma (HL) is highly effective with survival rates exceeding 90%. However, HL treatment affects gonadal function and HL survivors were proven to be at risk of premature ovarian insufficiency. In effort to reduce late effects, treatment protocols were adapted and toxic procarbazine was successfully omitted. The current EuroNET-PHL-C2 protocol aims to reduce use of radiotherapy by intensifying chemotherapy. The cumulative dose of cyclophosphamide is increased by 25% in the intensified treatment-arm, the impact of this change in therapeutic protocol on gonadal function is currently unknown. Therefore, a fertility study was incorporated in the EuroNET-PHL-C2 study. Study design, size, duration This international, prospective, multicenter cohort study is embedded in the EuroNET-PHL-C2 study, an European phase-3 treatment study evaluating the effectivity of HL treatment with OEPA-COPDAC (OEPA: vincristine sulfate (oncovin), etoposide, prednisolone and doxorubicin (adriamycin); COPDAC: cyclophosphamide, vincristine sulfate (oncovin), prednisone and dacarbazine) versus OEPA-DECOPDAC (DECOPDAC: COPDAC with additional doxorubicin and etoposide) in a randomized setting. In the present fertility add-on study, 205 (104 girls, 101 boys) patients were included between January 2017 and September 2021. Participants/materials, setting, methods Female patients, aged &amp;lt;18 years, treated according to the EuroNet-PHL-C2 protocol for classical HL, were recruited across 18 sites (the Netherlands, Belgium, Germany, Austria, Czech Republic). All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle were evaluated over time (at diagnosis, during- and directly after treatment, 2 years post-diagnosis) and compared between OEPA-COPDAC and OEPA-DECOPDAC treatment groups. Moreover, use of available fertility preservation treatments was evaluated. Main results and the role of chance In the present analysis, 100 girls were included of whom 88 completed 2 years of follow up. Median age at diagnosis was 15 years (7-18), 8 girls were prepubertal and 92 post pubertal (87% postmenarchal). 17 girls were diagnosed at an early stage of HL (TL1) and 83 in more advanced stages (TL2/TL3, 66% received COPDAC and 33% DECOPDAC). 5 patients (5%) were irradiated in the pelvic area. Of the 46 postmenarchal girls who did not receive hormonal contraceptives during treatment, 33 (72%) experienced treatment-induced amenorrhea, at least 4 (12%) had persisting amenorrhea at 2 years post-diagnosis. 4 girls (22%) who stopped taking hormonal contraceptives after treatment had no (return of) spontaneous cycle. 2 girls (2%) underwent ovariopexy. 4 girls cryopreserved oocytes before treatment and 12 cryopreserved ovarian tissue (OTC). 15 (15%) received GnRH analogues as a co-treatment. Data on AMH-levels up to 2 years post-diagnosis will be available by April 2023. Change in AMH will be evaluated, comparing number of received chemotherapy-cycles (3/4/6), DECOPDAC versus COPDAC and pubertal stage at time of diagnosis. Additional analyses will be performed to assess the impact of applied fertility preservation methods on gonadal function (i.e. AMH levels after OTC or receiving GnRH agonist). Limitations, reasons for caution The current analysis included data up to 2 years post-diagnosis. Potential recovery or late emerging effects of treatment remain unknown. The studied population comprises young girls with diagnosis of HL often concurring with pubertal transition, during which AMH levels naturally rise. SD z-scored will be used to analyze AMH results. Wider implications of the findings The fertility add-on study is the first study to prospectively evaluate reproductive markers in children treated for HL. Study results are highly valuable to determine effect of the proposed new treatment regimen for childhood HL on fertility . Trial registration number Clinicaltrials NCT02684708; EudraCT number 2012-004053-88

106 Background: Fertility is important to many young breast cancer survivors (YBCS), who face difficult decisions on whether to undergo fertility preservation prior to treatment. Because few longitudinal data assessing decisional regret are available, the objectives of this study were to assess longitudinal changes in decisional regret on fertility preservation following breast cancer diagnosis; determine if fertility preservation treatment decisions are related to decreased decisional regret. Methods: From 3 academic breast cancer programs, 169 YBCS younger than age 45 were recruited at diagnosis between 2009 and 2012 and followed prospectively for ovarian function. Participants completed questionnaires on fertility preservation choices and the Decisional Regret Scale (DRS) during study visits every 6 months for up to 5 years. DRS is scored 0 (no regret) to 100 (highest regret). DRS was dichotomized as none versus any decisional regret. Generalized linear models estimated the change in DRS over time and the association between patient characteristics and DRS. Results: Mean age at diagnosis was 38.7 (SD 4.8). Median total follow-up was 176 days (IQR 84 to 1415 days). Enrollment DRS was available for 89 women; 48% reported decisional regret about fertility preservation (median DRS=20). Participants worried about future fertility were more likely to report decisional regret (p=0.009). 31% underwent fertility preservation, but this was not associated with decisional regret (p=0.65). In repeated measures analysis for the entire cohort, no significant change in DRS occurred over this time period (OR 0.8, 95% CI 0.4-1.7). Worry about future fertility remained significantly associated with DRS over time (OR 55.1, 95% CI 7.7-395.1). Conclusions: In a cohort of YBCS, experiencing decisional regret about fertility preservation persists for years after diagnosis. Those worried about future fertility are more likely to experience decisional regret regarding fertility preservation.

Many transgender and gender diverse (TGD) people want to have biologically related children. This review summarizes and discusses the options for fertility treatment and preservation in TGD adults and adolescents, with an emphasis on gender-affirming hormone therapy in the context of fertility treatment, clinical management strategies to minimize gender dysphoria during treatment and major factors in future use of cryopreserved gametes. Years of growing research demonstrate that TGD people desire fertility counseling and family building; however, social and medical factors can impact future fertility options. Fortunately, TGD individuals have many viable options for family building using their own gametes and/or reproductive organs. However, the nuanced ways in which different gender-affirming treatments affect reproduction, the interplay with nontreatment-related infertility factors and mitigation of likely dysphoria triggers are all critical to actual utilization. This review focuses on fertility treatment and preservation options for TGD patients and highlights these influential social and medical factors. Fertility treatments may be associated with worsening gender dysphoria in TGD people, and an affirming clinical environment and conscientious provider approach is paramount to treatment success. However, reducing gender dysphoria can also require specific changes to medically assisted reproduction and sperm collection protocols, some of which carry the potential for diminished outcomes or unknown effects. Adolescents undergoing fertility preservation treatments may need more support or additional protocol modifications, and outcomes may be poorer in this age group compared with adults. Testicular and ovarian tissue cryopreservation may present a fertility preservation option for prepubertal TGD children; however, in vitro gamete maturation remains experimental in this situation.

Introduction In recent decades, the living conditions of breast cancer (BC) survivors have received particular attention, especially among the youngest who face problems related to fertility and sexuality. The main objective of this population-based study was to identify clinical, social and economic determinants of sexuality, fertility and Health Related Quality of Life (HRQoL), and describe other living conditions of young BC survivors in France. Methods Non-metastatic invasive BC women diagnosed from 2009 to 2016, aged ≤ 40 years at diagnosis were identified through the FRANCIM Network. Participants completed self-reported questionnaires including standardized measures (sexuality, HRQoL, anxiety, depression, social deprivation and social support), and fertility issues from June 2021 to December 2022. Sexuality profiles were identified by ascending hierarchical classification and fertility profiles were identified by latent class models. The main determinants of HRQoL were identified using mixed regression model. Results In total, 563 BC survivors from 14 French cancers Registries participated in the survey (response rate of 31%). The mean age at diagnosis was 35.9 (SD=3.8). Main tumors characteristics were AJCC stage 2-3 (61%), Hormone Receptor positive (76%), HER2 positive (24%), and Tumor grade ≥2 (91%). Patients underwent lumpectomy (72%), chemotherapy (85%), radiotherapy (85%), endocrine therapy (71%) and targeted therapies (23%). More than 5 years after diagnosis, 48% reported sexual dysfunction. About 47% of women received information about the impact of BC treatment on fertility, and 34% about fertility preservation. Among 18% of women who had a pregnancy project at diagnosis, 35% became pregnant after treatment. The number of spontaneous pregnancies decreases from 97% before diagnosis to 36% after treatment whereas the number of pregnancies with Medically Assisted procreation increases respectively from 8% to 10%. The average score of general health scale was 60.9. The highest average score of HRQoL was in the physical functioning scale (82.2) and the lowest was in vitality (48.2). Ascending hierarchical clustering allowed to identify 3 distinct sexuality profiles from worse sexual function to better respectively: profile 1 (20%), profile 2 (30%) and profile 3 (50%) of the studied population. Social deprivation and treatment with endocrine therapy (especially tamoxifen) were associated with an increased risk of sexual dysfunction. We identified 3 classes using a latent class model. In class 1, women had a pregnancy project at diagnosis but few of them had children and were referred to a reproduction specialist. At the end of treatments, the pregnancy rate was high in this group. Class 2 includes women who have a pregnancy project at diagnosis and who have given up at the end of treatment. At diagnosis, women in class 3 had children and had no specific pregnancy plans and they were menopausal at time of study with therefore a low rate of pregnancy after treatments. Classes differed in age at diagnosis (p=0.0000), fertility preservation (p=0.0000), information received about treatment impact on fertility (p=0.0002) and fertility preservation (p=0.0000), comorbidities (p=0.0040) and income (p=0.0000). The main determinants of general health were anxiety (p=0.0006), depression (p&amp;lt; 0.0001) and comorbidities (p= 0.0065). Conclusions This study showed that more than five years after the diagnosis of BC, almost one in two young BC survivors, diagnosed before 40 years old, experienced difficulties related to sexuality. Specific interventions in the field of supportive care (recourse to specialists, psychological support and improvement of communication within the couple) for this population should focus in managing sexual dysfunction and improving HRQoL. It would also be suitable for women to receive the necessary information on fertility at diagnosis at diagnosis in order to prepare them for after cancer. Citation Format: Emerline Assogba, Caroline Mollévi, Anne-Sophie Woronoff, Agnès Dumas, Ariane Mamguem, Charles Coutant, Isabelle Desmoulins, Sylvain Ladoire, Sandrine Dabakuyo. Sexuality and fertility profiles, Health-Related Quality of Life and other living conditions of young breast cancer survivors in France: a national cross-sectional study by the French Network of Cancer Registries (FRANCIM) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-04.

Long term pregnancy outcomes of women with cancer following fertility preservation: A systematic review and meta-analysis