Fertility-preserving Treatment Research Articles

Oncological safety of fertility preservation treatment in ovarian cancer: A Spanish multicenter study.

To assess the safety of fertility-sparing treatments for early-stage ovarian cancer in women younger than 40 years old. We performed a retrospective multicenter study including women aged 18-40 years diagnosed with early-stage (FIGO I-II) ovarian cancer in 55 Spanish hospitals, from January 2010 to December 2019. Benign and borderline tumors were excluded, as well as advanced stages (FIGO III-IV). All perioperative characteristics and follow-up data were collected and analyzed. Standard staging surgery (SSS) was compared with fertility-sparing surgery (FSS) in terms of oncological outcomes. In all, 366 women were included; 327 (89.3%) were stage I. Among all patients, 216 (59%) underwent SSS and 150 (41%) FSS. Up to 208 (56.8%) patients did not have children, but only 12 (3.2%) had oocyte preservation before treatment. Patients in the FSS group compared with the SSS group showed a non-significant difference in recurrences (8% vs. 9.3%, respectively; P < 0.711) and deaths (1.3% vs. 4.8%, respectively; P = 0.211) during the follow-up. No significant differences were found between epithelial and non-epithelial ovarian cancer both in recurrences (7.1% vs. 8.8%, respectively; P = 0.771) and in deaths (1.4% vs. 1.3%, respectively; P = 1) among patients who underwent FSS. FSS seems a safe option for treatment of early-stage ovarian cancer in patients who want to preserve fertility, either for epithelial and non-epithelial histology.

Planned Immediate Chemotherapy and Cryopreservation of Oocytes or Embryos for Fertility Preservation in Women with Malignancies.

Purpose: Oocyte and embryo cryopreservation before gonadotoxic treatment are established methods to increase the likelihood of live births. Although several sociodemographic factors were found to be associated with undergoing fertility preservation (FP) treatment, clinical characteristics such as planned immediate chemotherapy were not fully investigated. We aimed to investigate whether the planned immediate chemotherapy is related to the decision to undergo oocyte/embryo cryopreservation for FP with adjustment for other clinical characteristics. Methods: This institutional cohort study included 491 premenopausal women aged 19 years or older who visited the FP clinic at a tertiary medical center between 2006 and 2019. The primary outcome was whether the participants underwent oocyte/embryo cryopreservation. We evaluated the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of undergoing oocyte/embryo cryopreservation according to whether immediate chemotherapy was planned using univariable and multivariable logistic regression. Results: Women scheduled for immediate chemotherapy were much less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.46, 95% CI 0.27-0.76) in univariable logistic regression analysis. After adjustment for covariates such as marital status, type of malignancies, and calendar year period, women scheduled for immediate chemotherapy were still less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.31, 95% CI: 0.17-0.56). The association was not different according to the type of malignancies (p for interaction = 0.13). Regarding breast cancer, the OR for undergoing oocyte/embryo cryopreservation in women scheduled for immediate chemotherapy was robust compared with those not planned for immediate chemotherapy (OR = 0.25, 95% CI: 0.12-0.53). Conclusion: The present study demonstrated that planned immediate chemotherapy was negatively associated with undergoing oocyte/embryo cryopreservation. This information can be helpful for FP counseling.

Fertility Treatment and Preservation Options for Transgender and Gender Diverse People.

Years of growing research demonstrate that transgender and gender diverse (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 non-treatment 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 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.

REPRODUCTIVE HEALTH IN TRANS AND GENDER-DIVERSE PATIENTS: Psychosocial counseling of transgender and gender-diverse individuals in fertility and reproductive medicine: a narrative review.

Transgender and gender-diverse (TGD) people have similar desires for parenting as cisgender individuals but are likely to face greater barriers in accessing fertility treatment than their cisgender peers. Mental health professionals are well-positioned to advocate for and support TGD individuals seeking fertility care through pre-fertility treatment implications counseling regarding the psychosocial aspects of fertility treatment and family building. Transgender and gender-diverse (TGD) individuals experience significantly greater all-cause mortality and mental health disparities compared to their cisgender peers. Gender-affirming hormone therapy (GAHT) is a safe and effective treatment option for gender dysphoria that dramatically improves psychosocial health outcomes but may adversely impact fertility. Medical society guidelines recommend medical fertility preservation (FP) counseling and pre-fertility treatment psychoeducational implications consultation from qualified, reproductive mental health professionals (MHPs) for TGD individuals pursuing FP or third-party reproductive treatment. However, sparse literature exists specific to the structure of mental health psychoeducational consultation for TGD individuals pursuing FP. This narrative review highlights important areas for discussion in pre-fertility treatment mental health consultations. Results indicate that implications counseling should be conducted by an MHP with specialized training in reproductive mental health with TGD populations to reduce the risk of harm and promote successful emotional navigation of fertility treatment. Such counseling should be psychoeducational and not gatekeeping in nature and may include consideration of the psychosocial (e.g. emotional, relational, ethical, spiritual, social) risks and benefits of various family-building options. During these consultations, TGD individuals can explore their hopes and fears related to fertility and future family-building plans and discuss realistic treatment expectations, individual strengths, coping and communication strategies, and identify key support network members who may aid in navigating the fertility treatment process. MHPs can provide referrals to appropriate resources if necessary to help TGD individuals navigate treatment while coping with psychological symptoms and promoting behavior change.

Critical postpartum bleeding caused by an acquired uterine arteriovenous malformation: A Case Report

Introduction Postpartum uterine bleeding is a common occurrence in the field of Obstetrics and varies in severity from harmless to life- threatening. The majority of the cases are due to atony, retained tissue or lesions in the birth canal, making up more than 99% of the cases. However, rare causes, such as structural abnormalities and coagulopathies, are important to keep in mind during diagnostics, when the common causes of postpartum bleeding are ruled out, particularly when the symptoms present in an unconventional manner. Methods A case report of a healthy woman presenting with acute life-threatening postpartum bleeding due to an acquired arteriovenous malformation of the uterus. Results A 43-year-old healthy woman presented with acute life-threatening gynecological bleeding 16 days after acute caesarean section. Ultrasound raised the suspicion of arteriovenous malformation. However, due to uncertainty of the diagnosis no initial treatment was preformed until the patient presented with heavy bleeding once more, resulting in a life-saving hysterectomy. Conclusion Arteriovenous malformation is an important diagnosis to consider, as early and effective diagnostics brings the opportunity for a safe and fertility-preserving treatment in the form of radiological coiling embolization. Advances in ultrasound skills of clinicians has made fast and bedside diagnostics possible, therefore the number of hysterectomies should decrease in favor of fertility-preserving treatment.

Fertility preservation in pediatric central nervous system tumors: A report from the Children's Oncology Group.

The Oncofertility Consortium Pediatric Initiative Network has published recommendations about the risks of infertility due to gonadotoxic therapy. We abstracted gonadotoxic therapies from central nervous system (CNS) Children's Oncology Group (COG) protocols between 2000 and 2022. We assigned them as unknown, minimal, significant, or high levels of increased risk for gonadal dysfunction/infertility. Seven of 11 CNS protocols placed patients at a high level of risk in at least one treatment arm. Males (7/11) were most commonly at a high level of risk, followed by pubertal females (6/11) and prepubertal females (5/11), highlighting the importance of pre-treatment counseling regarding fertility preservation interventions in this population.

Reproductive Health in Trans and Gender Diverse Patients: Effects of transmasculine gender-affirming hormone therapy on future reproductive capacity: clinical data, animal models, and gaps in knowledge.

Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study. Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.

O-121 Assisted Reproductive Technology (ART) in Europe 2021 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium

Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2021 as compared to previous years and what are the main trends over the years? Summary answer The 25th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, outcomes for IUI cycles are similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analyzed by the European IVF-monitoring Consortium (EIM) and reported in 23 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31, 2021, in 34 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials, setting, methods In all 1155 clinics offering ART services in 34 countries reported a total of 910 470 treatment cycles, involving 115 567 with IVF, 346 183 with ICSI, 311 487 with frozen embryo replacement (FET), 62 694 with preimplantation genetic testing (PGT), 69 883 with egg donation (ED), 246 with IVM of oocytes and 4410 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1242 institutions offering IUI in 29 and 21 countries, respectively. A total of 139 350 treatments with IUI-H and 45 532 treatments with IUI-D were included. A total of 28 692 fertility preservation (FP) interventions from 15 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and post-pubertal patients were reported. Main results and the role of chance In total, 1155 IVF clinics participated (81.4% of registered clinics in the participating countries). Next to these also 1242 IUI units reported their data. In the 34 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2021 were similar to those observed in 2020 (26.2% and 43.3% versus 25.4% and 40.9%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2020 (23.9% en 45.7% versus 25.2% and 45.3%). Also after FET with own embryos, the PR per thawing is stabilizing, 35.0% in 2020 and 36.2% in 2021. After ED the PR per fresh embryo transfer was slightly increased to 53.1% (51.3% in 2020) and per FOR 45.5% (43.9% in 2020). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 60.2%, 34.8%, 1.8% and 0.2% of all treatments, respectively (corresponding to 57.9%, 37.5%, 2.1% and 0.2% in 2020). This resulted in a proportion of singleton, twin and triplet DRs of 90.4%, 9.5% and 0.1%, respectively (compared to 88.9%, 10.9% and 0.2%, respectively in 2020). Treatments with FER in 2021 resulted in twin and triplet DR of 7.0% and 0.1%, respectively (versus 7.9% and 0.1% in 2020). After IUI, the DRs remained similar at 9.2% after IUI-H (8.8% in 2020) and at 14.0% after IUI-D (12.5% in 2020). Twin and triplet DRs after IUI-H were 7.4% and 0.2%, respectively (in 2020: 7.9% and 0.4%) and 5.9% and 0.2% after IUI-D (in 2020: 5.7% and 0.1%). The majority of FP interventions included the cryopreservation of oocytes (n= 11 966 from 15 countries) and of ejaculated sperm (n=14 688 from 15 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract, some countries were not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 25th ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived live births in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine.

O-245 Is AMH testing relevant for fertility preservation in young oncology patients?

Abstract As the prevalence of cancer in young people rises, and with improved survival rates such that over 80% of young cancer patients can expect to recover, future fertility and having their own family has become an important consideration which needs to be addressed. Best-practice oncofertility management includes initial discussion, assessment of fertility risk and medical risk, and consideration of preservation strategies prior to commencement of potentially gonadotoxic therapy, where possible, as well as post cancer-treatment fertility care. The window of opportunity for oocyte cryopreservation and/or ovarian tissue cryopreservation may be very limited. Therefore it is of paramount importance that a patient’s medical condition, gonadotoxicity risk, and current reproductive health and potential are considered when planning fertility preservation. Antimullerian hormone (AMH) is one of a group of tests performed which can assist with planning treatment and with counselling regarding the likely yield of a cycle. Knowledge regarding pre-treatment AMH, along with a patient’s age and the type of cancer treatment, may also assist with counselling regarding the likelihood of recovery of fertility after completion of this treatment. However, there are many factors which affect AMH levels, and it is well-known that the results of stimulation can be very variable, as can be the long-term impact of the potentially gonadotoxic treatment. Hence an AMH test, while useful, needs to be contextualized as being only one of many factors to be considered when planning optimal (in terms of yield and safety) fertility preservation treatment and advising re future fertility.

P-367 Letrozole or Tamoxifen co-administration during fertility preservation of breast cancer patients: a retrospective cohort study

Abstract Study question How do fertility preservation (FP) outcomes differ between breast cancer patients stimulated with FSH and Tamoxifen versus FSH and Letrozole? Summary answer Letrozole and Tamoxifen co-administration yielded similar number of retrieved and cryopreserved oocytes/embryos, as well as similar oocyte maturation and fertilization and rates. What is known already Oocyte/embryo cryopreservation is recommended before initiation of chemotherapy in cancer patients. The co-administration of Tamoxifen, a selective estrogen receptor modulator, or Letrozole, an aromatase inhibitor, during ovarian stimulation with gonadotropins, are used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the optimal choice between the two is still unclear and with no sound evidence. Study design, size, duration Retrospective cohort study of all FP treatments of newly diagnosed breast cancer patients in two tertiary centers between 2000-2022. Collected data included 354 FP cycles of 290 patients and compared treatment parameters and outcomes of Tamoxifen or Letrozole co-administration. Participants/materials, setting, methods Breast cancer patients who underwent FP before chemotherapy were included. Patients with a history of radiation or gonadotoxic treatment, as well as those undergoing other fertility preservation treatments, such as ovarian tissue cryopreservation were excluded. Main results and the role of chance Overall, 215 Letrozole and 139 Tamoxifen treatment cycles were compared, with no significant demographic differences. Treatments with Letrozole had higher FSH dosages (3970IU vs. 2839IU, p &amp;lt; 0.001) but shorter duration (9.7 vs. 10.5 days, p &amp;lt; 0.001). The Letrozole group achieved lower peak E2 levels and endometrial thickness (1508pmol/L, 8.1mm vs. 8760pmol/L, 9.5mm, p &amp;lt; 0.001). The mean number of retrieved oocytes was comparable between the groups (13.6 with Letrozole vs 14.7 with Tamoxifen, p = 0.06). In 122 Letrozole and 46 Tamoxifen patients that underwent strictly oocytes cryopreservation the mean number of cryopreserved oocytes was comparable (11 vs. 12.1, p = 0.21). Moreover, in embryo cryopreservation cycles of 71 patients treated with Letrozole compared to 76 patients with Tamoxifen, no difference was observed in the number of cryopreserved embryos (6.2 vs. 7.0, p = 0.12). Oocyte maturation rate among strictly oocyte preservation cycles was comparable (86% with Letrozole vs. 83% with Tamoxifen, p = 0.80), as were fertilization rates in embryo cryopreservation cycles (62% vs. 63%, p = 0.8 and 71% vs. 76%, p = 0.3 in IVF and ICSI with Letrozole and Tamoxifen, respectively). Multivariate analysis, controlling for potential confounders showed no significant correlations between Tamoxifen or Letrozole co-administration and the number of retrieved oocytes or oocyte maturation rate. Limitations, reasons for caution The primary limitation of our study is its retrospective design and the variation in treatment duration and gonadotrophin dosages among groups. Wider implications of the findings This study provides reassurance that both Tamoxifen and Letrozole are equally effective options when co-administered in FP treatments of breast cancer patients. Trial registration number not applicable

P-361 Preserving fertility prior to hematopoietic stem cell transplant in post-pubertal women with sickle cell anaemia

Abstract Study question Can fertility preservation (FP) in women with sickle cell anemia (SCA) be linked to an increased risk of hematopoietic complications? Summary answer Only one participant on sixteen in our series had to discontinue the ovarian stimulation due to a complication related to a painful vaso-occlusive crisis (VOC). What is known already SCA is one of the most common severe monogenic diseases worldwide. It is a multisystemic disorder characterized by anaemia, increased haemolysis, and VOC. Despite advances in management, patients remain at a high risk of significant morbidity, especially increased thromboembolic events and early death. With the introduction of hematopoietic stem cell transplantation(HSCT) for non-malignant conditions, there is now a curative treatment for this debilitating condition. The myeloablative regimens for HSCT may impact ovarian reserve; therefore consideration of FP could be recommended. There is limited data on FP in this context and the risk of hematopoietic complications such as VOC is unclear. Study design, size, duration Cohort of women with SCA consulting at our center for FP before a HSCT project between 2016 and 2023. FP modalities were oocytes vitrification after ovarian stimulation and ovarian tissue cryopreservation (partial unilateral ovariectomy under laparoscopy). A protocol for the prevention of the risk of VOC, including hydration, oxygen therapy, and warming ± transfusion exchanges and for thromboembolic events was initiated before and during FP treatment, tailored on a case-by-case basis with the referring haematologist. Participants/materials, setting, methods The data related to hematopoietic complications (including VOC and thromboembolic event) [ps1] during FP were collected. Additionally, data on the follow-up of SCA, including received and planned treatments post-FP, were collected. This encompassed information on the completed FP treatments, preventive measures for SCA complications, and the outcomes of FP. Descriptive analysis was conducted. Main results and the role of chance During the study period, sixteen women affected with SCA aged 15–37 years have consulted for FP in our center. The mean age and BMI were 28.43±6.66 years and 21.97 ±3.46 respectively. The mean AMH level and antral follicle count were 1.77±1.70 and 15.83 ±7.12 respectively. Twelve patients underwent oocytes vitrification after mulfifollicular ovarian stimulation (OS), two had ovarian tissue cryopreservation, and 1 underwent both technics. One patient, initially planning for OS, cancelled after counselling. Among the 13 women that received an OS, 18 cycles were performed in total. The mean number of OS cycles per patient was 1.38±0.73. Protocols were antagonist (n = 16) or short agonist protocols (n = 2). The mean duration of gonadotropin treatment was 9.91±1.84 days, and the mean total gonadotropin dose was 3187.5±711.8 IU. Five OS were cancelled before oocyte retrieval because of an insufficient ovarian response. The mean number of oocytes retrieved was 8.83±5.61 per cycle. The mean number of cryopreserved oocytes was 12.00±5.66. One patient had to discontinue the OS due to a complication related to a painful VOC at 3 days of stimulation. As recommended, the hydroxycarbamide treatment was temporarily suspended to perform the FP. For patients who underwent unilateral partial ovariectomy, no complications were reported. Limitations, reasons for caution The main limitation is that this study is a small, retrospective case series; however, this represents the largest series to date. Wider implications of the findings Although limited, current data suggest that FP with specific conditioning does not pose a significant risk of complications in patients with SCA who are to undergo gonadotoxic treatment for HSCT. Trial registration number NA

P-366 Short- and long-term safety outcomes in patients undergoing fertility preservation (FP) with controlled ovarian stimulation prior to chemotherapy

Abstract Study question The Impact of pre-chemotherapy fertility preservation (FP) with controlled ovarian stimulation (COS) on mortality and complications in cancer patients Summary answer The 5-year survival was higher in women who proceeded with FP than those who did not. What is known already FP in the form of egg/embryo freezing is a well-established option to preserve fertility in patients requiring gonadotoxic treatment. This method introduces a slight delay in chemotherapy initiation, raising theoretical concerns about its impact on long-term patient outcomes. Additionally, safety concerns exist for estrogen-sensitive pathologies. However, data on safety outcomes, especially mortality and cancer recurrence in women undergoing fertility preservation, remain limited. Study design, size, duration This study utilized a prospectively collected database of 603 patients referred from the UK South and South East cancer network for fertility preservation to a tertiary Assisted Conception Unit between 2003 and 2019. Participants/materials, setting, methods All female patients attended the Fertility Preservation Service post-cancer diagnosis to discuss options. Patient demographics, stimulation details, and treatment outcomes were recorded. Living status was confirmed up to January 2024 through Health Record Registry. Data analysis included basic demographics, hazard ratios, and 5-year survival analysis, with a log-rank test comparing patients who received or did not receive fertility preservation treatment. Main results and the role of chance As many as 603 patients were counselled re: FP over the studied period. The biggest majority of patients n = 320 (53%) had a diagnosis of breast cancer, followed by 67 patients (11.1%) presenting with lymphomas. The majority of counselled patients (n = 340 (56.4%)) went ahead with fertility preservation. Mean age of participants was 32.7 with an average BMI of 24.6, average AMH of 19.2 pmol/L, and median AFC of 15. Short term complication was estimated at 2% of the sample. Successful stimulation was noted in almost all cases (cancellation rate 1.5%) requiring on average 14 days to complete the treatment. A short protocol was mainly used (98% of cases) with a median daily FSH injection at 300 IU/L and an average oocyte yield of 14. Mortality in patients who received fertility preservation was estimated and the respective hazard ratio was 0.74 (95% CI 0.47 to 1.15, p = 0.18). With regards to survival, the log-rank test yielded a chi-square value of 3.9 with 1 degree of freedom. The resulting p-value was 0.05, indicating a statistically significant difference in survival probabilities between patients who underwent fertility preservation compared to those who did not (p = 0.05). Limitations, reasons for caution Information on the cause of death was unavailable, limiting the ability to minimize bias and estimate disease recurrence. However, the young age of the patient population reduces the likelihood of death due to unrelated medical conditions. Wider implications of the findings The data suggests that fertility preservation with controlled ovarian stimulation is a safe option for cancer patients. This finding provides reassurance to patients considering this well-established fertility treatment, offering realistic chances of survival. Trial registration number not applicable

Suspected myometrial invasion on MRI is correlated with worse outcomes of fertility-preserving treatment in young women with endometrial cancer

PurposeMyometrial invasion of endometrial cancer (EC) impairs the effectiveness of progestin-based treatment and results in high risks of disease progression and relapse. However, it is difficult to decide whether myometrial invasion exists when suspected endometrial invasion is detected on magnetic resonance imaging (MRI). This study developed an MRI-guided hysteroscopic precise en bloc resection method to actually diagnose myometrial invasion in patients with EC and suspected myometrial invasion on MRI. The fertility-preserving outcomes of patients with EC and suspected myometrial invasion on MRI but negative pathological findings after en bloc resection was also evaluated.Materials and methodsEC patients with suspected myometrial invasion on MRI (n = 38) were prospectively enrolled and evaluated. Suspected myometrial invasion was identified on MR images and resected via an en bloc resection technique (resecting the endometrial lesion, basal layer, and underneath myometrium en bloc) under hysteroscopy for pathological examination. Patients with negative pathological findings received progestin-based conservative therapy. The clinical characteristics and fertility-preserving outcomes of these patients were compared with those of patients without any evidence of myometrial invasion on MRI (n = 98, reference group).ResultsAmong patients with suspected myometrial invasion on MRI, myometrial invasion was pathologically excluded in 29 patients (non-MI group). The cumulative complete response rate was lower in the non-MI group than in the reference group at the 8th month (43.4% vs. 64.9%, P = 0.040) and was not significant at the 18th month (87.5% vs. 96.8%, P = 0.11). The 24-month cumulative relapse rate was 31.2% in the non-MI group, versus 0% in the reference group (P < 0.0001).ConclusionMyometrial invasion was pathologically confirmed in approximately one-fourth of patients with suspected myometrial invasion on MRI. However, suspected myometrial invasion on MRI with negative pathological findings was correlated with worse fertility-preserving outcomes in young women with endometrial cancer.

Current research of Assisted Reproductive Technology for women with early endometrial cancer and atypical endometrial hyperplasia after conservative treatment.

As the incidence of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) has been increasing, and has shown young trend. It is crucial to study the fertility-preserving treatment of endometrial lesions and fertility-promoting protocols. Age, obesity, and irregular ovulation are not only high-risk factors for endometrial lesions but also key factors affecting female fertility. Assisted reproductive technology (ART) can significantly improve pregnancy outcomes in patients with AEH and EC after conservative treatment. Based on the existing studies, this article reviews the progress of research on pregnancy outcomes of ART and its influencing factors in such patients. It helps physicians in providing optimal fertility guidance.

Fertility-Preserving Treatments and Patient- and Parental Satisfaction on Fertility Counseling in a Cohort of Newly Diagnosed Boys and Girls with Childhood Hodgkin Lymphoma.

The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling. A total of 101 boys and 104 girls were included. Most post-pubertal boys opted for semen cryopreservation pre-treatment (85% of expected). Invasive FP treatments were occasionally chosen for patients at a relatively low risk of fertility based on scheduled alkylating agent exposure (4/5 testicular biopsy, 4/4 oocyte, and 11/11 ovarian tissue cryopreservation). A total of 17 post-menarchal girls (20%) received GnRH-analogue co-treatment. Furthermore, 33/84 parents and 26/63 patients responded to the questionnaire. Most reported receiving fertility counseling (97%/89%). Statements regarding the timing and content of counseling were generally positive. Parents and patients considered fertility counseling important (94%/87% (strongly agreed) and most expressed concerns about (their child's) fertility (at diagnosis 69%/46%, at present: 59%/42%). Systematic fertility counseling is crucial for all pediatric cHL patients and their families. FP treatment should be considered depending on the anticipated risk and patient factors. We encourage the development of a decision aid for FP in pediatric oncology.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

The Analysis of in vitro Fertilization Outcomes after Fertility-Preserving Therapy for Endometrial Hyperplasia or Carcinoma.

This study aimed to evaluate the clinical efficacy of fertility-preserving therapy through in vitro fertilization (IVF) procedures in women who were pathologically diagnosed with endometrial hyperplasia or carcinoma. A retrospective cohort study on fertility-preserving therapy was conducted. Participants/Materials, Setting: A total of 82 women were enrolled who had simple endometrial hyperplasia (SH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), and endometrioid endometrial carcinoma stage IA (EC IA) and underwent IVF at Gangnam CHA fertility center between January 2008 and December 2020. The primary endpoints were oncologic outcomes and subsequent reproductive outcomes of patients who underwent fertility-preserving treatments analyzed by χ2 test or Fisher's exact test. Of the 82 patients, 33 had a cumulative clinical pregnancy (40.2%), and 25 had a cumulative live birth (30.5%) through IVF procedures following pathologic confirmation of complete remission or non-progressive status. The cumulative clinical pregnancy rates and live birth rates for SH were 50.0% and 30.0%, for CH were 37.8% and 28.9%, for CAH were 25.0% and 25.0%, and for EC were 38.5% and 38.5%, respectively. There were no significant differences in cumulative clinical pregnancy rates or live birth rates when comparing the four groups. There was a difference in endometrial thickness between medroxyprogesterone acetate (MPA) treatment group and intrauterine device (IUD) group (p = 0.036); however, there were no significant differences in clinical pregnancy rates among MPA, IUD, and MPA+IUD groups. Because of the retrospective nature of the study, many factors relevant to the treatment decision were not strictly controlled. All endometrial hyperplasia and carcinoma groups had competent cumulative live birth rates by IVF procedures. There may be differences in endometrial thickness depending on the treatment methods, but this does not affect clinical pregnancy rates. Therefore, the fertility-preserving treatment for endometrial hyperplasia and carcinoma is a safe and feasible method that results in good IVF outcomes.

Co-design and usability of an interactive web-based fertility decision aid for transgender youth and young adults.

To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design. TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale). Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores. We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy.

The aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care. Patients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes. Of 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker. This is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Abstract PO2-11-06: Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN trials

Abstract Background: The ability to predict and identify ovarian function loss accurately after anticancer treatment is important for appropriate oncofertility counseling and to aid in therapy decision making for young women with early breast cancer (eBC). Anti-Müllerian hormone (AMH) has been proposed as both a pre- and post-treatment predictor of subsequent permanent loss of ovarian function. The present biomarker analysis conducted within two randomized controlled trials (RCTs) in a large and well-characterized patient population with HER2+ eBC receiving homogeneous treatment aimed to assess AMH use, alone and in combination with other hormonal biomarkers, for predicting loss of ovarian function at 36 months from randomization, i.e. approximately 2 years after end of therapy. Methods: BETH (NCT00625898) and KAITLIN (NCT01966471) were RCTs investigating adjuvant chemotherapy (CT) plus anti-HER2 therapy in high-risk HER2+ eBC patients. For the purpose of the present analysis, only samples of patients receiving currently adopted treatments were used, i.e. cohort 1A (6 cycles of docetaxel/carboplatin+trastuzumab (T)) and cohort 2A (3 cycles of docetaxel plus T followed by 3 cycles of anthracycline- and cyclophosphamide-based CT) of BETH trial, and arm 1 (3-4 cycles of anthracycline- and cyclophosphamide-based CT followed by 3-4 cycles of taxane plus T plus pertuzumab (P)) of KAITLIN trial. Women selected for this analysis were ≤45 years with known premenopausal status, available serum samples at baseline (pre-treatment) and/or end of therapy and 36 months (± 6 months) from randomization (i.e. min of 2 samples in all cases). Selected samples were centrally tested measuring AMH, follicle stimulating hormone (FSH) and estradiol (E2) using Roche Elecsys assays. Permanent ovarian loss was defined as FSH &amp;gt;25 IU/L and E2 &amp;lt; 110 pmol/L at 36 months. Results: Of 194 included patients, 62 were from BETH and 132 from KAITLIN. 139 (71.6%) received both taxane and anthracycline- and cyclophosphamide-based CT and 55 (28.4%) taxane only. Pertuzumab was used in addition to trastuzumab in 132 (68.0%) patients. AMH values declined from baseline median 8.44 pmol/L to undetectable levels in many women at end of therapy (median 0.08 pmol/L), with partial recovery at 36 months (median 0.14 pmol/L). Ovarian loss at 3 years was observed in 56 women with AMH available at baseline (29.5%) and in 52 women with AMH available at end of therapy (29.7%). For prediction of ovarian loss, in ROC analysis, AMH measured at baseline showed AUC 0.784 (internally validated using bootstrap: 0.783). While age influenced risk of ovarian loss, addition to AMH only slightly improved AUC to 0.800 (internal validation: 0.795) while addition of baseline FSH and E2 did not improve prediction. AMH measured at the end of therapy showed AUC 0.741 (internal validation: 0.742), which increased slightly to 0.785(internal validation: 0.781) with addition of age but without improved prediction with the addition of FSH and E2. The combination of AMH at baseline and end of therapy increased prediction slightly to 0.808 (internal validation 0.806) and with addition of age added to 0.820 (internal validation: 0.806). Conclusions: These results support the use of pretreatment measurement of AMH in predicting loss of ovarian function in women withHER2+ eBC aged ≤45 receiving CT and anti-HER2 therapy. Measurement of AMH at end of treatment was comparably valuable to pretreatment and added slightly to the value of pretreatment sampling. Inclusion of ovarian function assessment by measuring AMH before commencing treatment can inform subsequent risk of ovarian function loss with value for fertility preservation counselling and treatment decisions. Further validation is required in larger cohorts. Citation Format: Matteo Lambertini, Deirdre Allegranza, Ruediger Laubender, Nadia Harbeck, Sandra Swain, Charles Geyer, Dennis Slamon, Gabriella Bobba, Chiara Lambertini, Sanne Lysbet De Haas, Eleonora Restuccia, Ines Vaz Luis, David Cameron, Ian Krop, Eric Winer, Richard Anderson. Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN trials [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 PO2-11-06.