For Fertility Preservation Research Articles

P-365 Fertility preservation in patients with borderline ovarian tumors: safety and reproductive outcomes

Abstract Study question Do borderline ovarian tumors (BOT) patients, undergoing controlled ovarian stimulation (COS) face higher recurrence risks, and what are the associated reproductive outcomes? Summary answer Even in advanced-stage or bilateral BOT, COS does not significantly impact recurrence rates. Additionally, COS for fertility preservation(FP)provides a viable option for future reproductive potential. What is known already The primary approach for treating BOTs involves surgical intervention, emphasizing complete tumor removal. Conservative surgery is an option for young women seeking to preserve reproductive potential. However, the recurrence risk following conservative surgery is significant, reaching up to 25%, necessitating repeat surgeries that impact ovarian reserve. Existing evidence on the safety of COS in terms of BOT recurrence remains inconclusive. Concerns about a potential association between COS and tumor progression persist, particularly in advanced-stage and bilateral disease cases. This study address these gaps in knowledge and provide more clarity on the safety of COS in BOT patients. Study design, size, duration A retrospective cohort study was conducted across two tertiary, university-affiliated medical centres: IRCCS San Raffaele Hospital, Milan, Italy, and SHEBA Medical Hospital, Tel-Aviv University, Israel. The study included 165 patients diagnosed with borderline ovarian tumors who underwent conservative surgery between 2012 and 2023. Participants/materials, setting, methods Participants aged 18-42 years with BOT (stages I-III) and undergoing conservative treatment were stratified into two groups: those opting COS for FP(41 patients)and a control group without such intervention (124 patients). COS involved GnRH antagonist random-start protocols utilizing menotropins and/or recombinant FSH. GnRH-agonist or hCG were used for triggering. Oocyte vitrification or fertilization and embryo freezing was performed. Statistical analyses, including Pearson’s chi-square, Fisher’s exact test, T test, and logistic regression, were employed for evaluation. Main results and the role of chance In the course of COS cycles and oocyte retrieval, no complications were observed. Among 165 participants, 33% experienced BOT recurrence over a median of 28.5 months (range: 12.7 to 42.7). Patients with recurrence were younger (29 vs. 32 years, P = 0.04), had advanced-stage (26 vs. 18, p < 0.0001), and bilateral disease (38% vs. 19%, p = 0.01). Of the 41 undergoing COS, 19 experienced recurrence, comparable to the control group (36 patients, p = 0.055). Notably, all COS-related recurrences were BOT histotype, not invasive carcinoma, managed through a second surgery. No significant differences in ovarian stimulation cycles (2.4 vs 1.7, p = 0.7) or retrieved oocytes (11.8 vs 10.6, p = 0.6) were detected between women with and without recurrence. In multivariate analysis, advanced disease significantly increased recurrence odds (aOR=3.7, 95% CI: 1.7-7.9, P < 0.001), while COS did not (aOR=1.7, 95% CI: 0.7-3.9, P = 0.16). This suggests that while age and disease stage play roles, COS alone may not significantly influence recurrence rates. Importantly, among women undergoing COS for FP, 17 achieved at least one pregnancy, totaling 24 pregnancies, with 18 live births. Six were spontaneous, and three used frozen embryos from FP cycles. This underscores the reproductive success of FP through COS, providing hope for fulfilling childbearing desires post-BOT diagnosis. Limitations, reasons for caution Limitations include the retrospective nature, a selection bias in the COS group, and the rarity of the disease leading to a small sample size. Despite these, the recurrence rate in the COS group was comparable to a systematic review, and caution is advised in interpreting these results. Wider implications of the findings Our study suggests that COS does not significantly contribute to recurrence risk in BOT patients, even in advanced stages. FP through COS enhances the likelihood of live births in these patients. While cautious interpretation is warranted, these findings offer hope and call for larger prospective studies to confirm these results. Trial registration number not applicable

Clinical Practice Guideline-Inconsistent Management of Fertility Preservation in Pediatric Cancer Patients in Community Settings: A Children's Oncology Group Study.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Overactivation or Apoptosis: Which Mechanisms Affect Chemotherapy-Induced Ovarian Reserve Depletion?

Dormant primordial follicles (PMF), which constitute the ovarian reserve, are recruited continuously into the cohort of growing follicles in the ovary throughout female reproductive life. Gonadotoxic chemotherapy was shown to diminish the ovarian reserve pool, to destroy growing follicle population, and to cause premature ovarian insufficiency (POI). Three primary mechanisms have been proposed to account for this chemotherapy-induced PMF depletion: either indirectly via over-recruitment of PMF, by stromal damage, or through direct toxicity effects on PMF. Preventative pharmacological agents intervening in these ovotoxic mechanisms may be ideal candidates for fertility preservation (FP). This manuscript reviews the mechanisms that disrupt follicle dormancy causing depletion of the ovarian reserve. It describes the most widely studied experimental inhibitors that have been deployed in attempts to counteract these affects and prevent follicle depletion.

Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

BackgroundThe indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation.MethodsWe conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome.ResultsForty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births.ConclusionsOocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

Body image disturbances in adolescent and young adult cancer patients confronting infertility risk and fertility preservation decisions

Purpose Body image is a major psychosocial concern for all cancer patients but can affect the adolescent and young adult (AYA) population in distinct ways. Similarly, the prospect of infertility and the fertility preservation process can create additional stress during cancer treatment. Discussions regarding infertility inherently implicate the body and its reproductive function, but downstream effects on self-perception have not been previously described. The aim of this study was to explore the experiences of AYAs as they considered their risk of infertility and options for fertility preservation (FP), specifically the ways in which this impacted body image and FP decision-making. Methods AYA cancer patients (n = 27) aged 12–25 years whose cancer and treatment conferred risk of infertility were recruited through electronic health record query at an NCI-Designated Comprehensive Cancer Center. Participants completed semi-structured interviews, which were recorded, transcribed, and deductively coded for themes related to information needs, knowledge of treatment effects on fertility, and reproductive concerns after cancer. Emergent, inductive themes related to body image were identified. Results Body image concerns, related to both physical appearance and body functioning emerged. Common concerns included anticipating change as it pertains to the body and its functions, physical discomfort, fear of judgment, and meeting expectations of the body. While these themes are broad in nature, they have been previously explored in relation to body image in general and their emergence in the oncofertility space provides guidance for further optimization of infertility and fertility preservation discussions. Conclusions AYA cancer patients experience a multitude of body image related disturbances when faced with the possibility of infertility and fertility preservation. In identifying and exploring these themes, future opportunities for improving oncofertility practice and discussions among AYAs with a focus on body image positivity are called upon.

Effects of meiotic stage-specific oocyte vitrification on mouse oocyte quality and developmental competence.

Acquisition of germinal vesicle (GV) stage oocytes for fertility preservation (FP) offers several benefits over in vivo matured oocyte cryopreservation following ovarian stimulation, particularly for cancer patients necessitating immediate treatment. Two FP approaches for GV oocytes are available: vitrification before in vitro maturation (IVM) at the GV stage (GV-VI) or post-IVM at the metaphase II (MII) stage (MII-VI). The optimal method remains to be determined. In this study, mouse oocytes were collected without hormonal stimulation and vitrified either at the GV stage or the MII stage following IVM; non-vitrified in vitro matured MII oocytes served as the control (CON). The oocyte quality and developmental competence were assessed to obtain a better method for immediate FP. No significant differences in IVM and survival rates were observed among the three groups. Nevertheless, GV-VI oocytes exhibited inferior quality, including abnormal spindle arrangement, mitochondrial dysfunction, and early apoptosis, compared to MII-VI and CON oocytes. Oocyte vitrification at the GV stage impacted maternal mRNA degradation during IVM. In addition, the GV-VI group demonstrated significantly lower embryonic developmental competence relative to the MII-VI group. RNA sequencing of 2-cell stage embryos revealed abnormal minor zygotic genome activation in the GV-VI group. Vitrification at the GV stage compromised oocyte quality and reduced developmental competence. Consequently, compared to the GV stage, oocyte vitrification at the MII stage after IVM is more suitable for patients who require immediate FP.

P-411 Cumulative live-birth rate after oocyte vitrification for fertility preservation (FP) in oncologic or benign conditions: a retrospective comparative monocentric study

Abstract Study question Does cumulative livebirth-rate (CLBR) after reutilization of vitrified oocytes differ between patients having undergone fertility preservation (FP) for oncologic (onco-FP) reason or benign conditions (benign-FP)? Summary answer Although CLBR per woman was lower in the onco-FP group, there was no statistically significant association in multivariate analysis between onco-FP and CLBR. What is known already Recent ESHRE guidelines reported oocyte vitrification after controlled ovarian hyperstimulation (COH) as an established option for FP. Although age at the time of oocyte vitrification remains the main predictive factor of success, several lines of evidence suggest that the use of COH or in vitro maturation (IVM), as well as the indication of FP, in particular the type of disease, may influence outcomes after devitrification. The present investigation aimed at clarifying this issue. Study design, size, duration Observational comparative, monocentric retrospective study including all patients having reused, between January 2014 and December 2021, their oocytes vitrified for oncologic or benign conditions between 2013 and 2021. Women having undergone FP for non-medical indication were excluded. Participants/materials, setting, methods Among the 2201 patients having vitrified their oocytes, 94 (4.7%) returned for reutilization. The primary objective was the comparison of CLBR between onco-FP (n = 48) and benign-FP (n = 46) groups. A logistic model was performed. Factors associated with the CLBR in univariate analysis were included in a multivariate model. A secondary analysis was performed, comparing the benign-FP group and 2 groups of onco-FP according to the use of COH (Onco-COH, n = 25) or in-vitro maturation (Onco-IVM, n = 23). Main results and the role of chance Overall, in comparison with benign FP, women with malignant diseases were younger (median [IQR]: 34.0 y [31.0;37.0] vs. 36.5 y [33.2;38.0], p = 0.04) and had fewer oocytes vitrified (median [IQR]: 6.0 [3.0;9.2] vs.15.5 [6.2;18.0]), p &amp;lt; 0.001). The CLBR in onco-FP and benign-FP groups were 14.6% (7/48), and 32.6% (15/46), respectively. In univariate analysis, the CLBR was significantly lower in the onco-FP group when compared with the benign-FP group: (OR [95%CI]: 0.35 [0.12;0.94], p = 0.04). However, this difference in the CLBR did not reach significance after multivariate analysis (OR [95%CI]: 0.38 [0.09;1.51], p = 0.18). As expected, age at the time of oocyte vitrification was negatively associated with CLBR (OR [95%CI]: 0.80 [0.67;0.92], p = 0.005), while the number of oocytes inseminated was positively related to CLBR (OR [95%CI]: 1.22 [1.08;1.40], p = 0.002). Unlike onco-COH, onco-IVM was associated with a significant decrease in CLBR when compared to benign-FP (only COH), in univariate analysis: 8.7% (OR [95%CI]: 0.20 [0.03;0.80], p = 0.04), without significance after multivariate analysis (OR [95%CI]: 0.37 [0.04;2.16], p = 0.29).The livebirth rate (LBR) per oocyte was 2.1% in the onco-IVM subgroup (3 babies for 141 oocytes thawed), 2.7% in the onco-COH subgroup (7 babies for 260 oocytes thawed) and 3.7% (18 babies for 479 oocytes thawed) in the benign-FP group. Limitations, reasons for caution The small size of our population was probably responsible for a lack of statistical power. The retrospective and monocentric nature of our study may also be a weakness. Furthermore, LBR per oocyte was analyzed without age-adjustment. Wider implications of the findings This study provides actual data on chances of achieving a livebirth after oocyte vitrification, according to the use of a COH or IVM and the context of FP, oncologic or benign conditions. Trial registration number not applicable

O-278 Medical and ethical perspectives of performing ovarian stimulation and oocyte cryopreservation for fertility preservation (FP) in adolescents: 5 years’ experience from a tertiary centre

Abstract Study question What are the medical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and what are the barriers to provision? Summary answer Oocyte cryopreservation for benign and malignant indications in adolescents is associated with unique medical and ethical challenges. What is known already An improvement in childhood cancer survival, increased transgender care and benign conditions such as haemoglobinopathies requiring stem cell transplant have led to higher representation of adolescent birth-registered females in FP clinics. FP in adolescents has increased complexities, both physical (pubertal stage, diagnosis) and psychological (accepting diagnosis, processing information, decision-making). Concerns relate to reliability of AMH in adolescents, anticipated response to ovarian stimulation and oocyte quality. Counselling and consenting young people and their families about fertility decisions, often alongside receiving a life-changing diagnosis, is an ethically complex area. Assessing capacity to consent is not straightforward. We report our clinical experience. Study design, size, duration This was a retrospective, observational cohort study of 26 adolescent birth-registered females aged 13 to 18 years who underwent ovarian stimulation and oocyte cryopreservation in a specialist unit for fertility preservation between 2018 and 2022. The primary outcome was oocyte yield, secondary outcomes included complications and drop-out rate. Participants/materials, setting, methods We included post-pubertal adolescent birth-registered females aged 13 to 18 years who were referred for fertility preservation for high risk of gonadotoxicity from treatment and who commenced ovarian stimulation for oocyte cryopreservation. Data was retrieved from a prospectively managed database. We noted demographic data, ovarian reserve, method of monitoring, response to ovarian stimulation and oocyte cryopreservation and route of egg collection. Documentation on counselling conversations and psychological maturity was retrieved from clinical records. Main results and the role of chance There were a total of 29 ovarian stimulation cycles performed in 26 adolescent birth-registered females aged between 13 and 18 years. Indications for fertility preservation included malignancy 62% (16/26), immunological disorders 19% (5/26), gender reassignment treatment 8% (2/26), recurrent ovarian cyst surgery 8% (2/26) and benign haematological disease 4% (1/26). The youngest was aged 13 years and 10 months at the time of egg collection. Minimum time from menarche to ovarian stimulation was 11 months. 23% (6/26) adolescents had previously received chemotherapy. AMH was 2.8-37 pmol/L and AFC 2-36. AFC correlated well with AMH in the majority. Random-start was performed in 54% (14/26) and dual stimulation in 12% (3/26). Number of cryopreserved oocytes was 3-45 and number of MII oocytes cryopreserved 3-35. Ultrasound monitoring was performed transabdominally in 88% (23/26) and transvaginally in 12% (3/26). Egg collection was performed transvaginally in all cases in this cohort, comprising adolescents from varying ethnicities. All cycles proceeded to completion. There were no complications in any cycle, including the 42% (11/26) performed for haematological malignancy. All adolescents were counselled in association with a family member to obtain informed consent. All were assessed as able to comprehend discussions. Limitations, reasons for caution There is limited data on performing oocyte cryopreservation in adolescents. Further studies expanding on our findings are needed to support clinicians to perform oocyte cryopreservation in this population. Concerns remain regarding increased aneuploidy rates in this age group compared to women in their 20s. Livebirth outcome data is needed. Wider implications of the findings This is the largest case series to date. Post-pubertal adolescents as young as age 13 can undergo ovarian stimulation and oocyte cryopreservation. Transvaginal egg collection is an accepted procedure when counselled appropriately. Clinician experience, correct setting and funding enable a permissive environment for oocyte cryopreservation in this population. Trial registration number N/A

Trends and outcomes of fertility preservation for girls, adolescents and young adults with Turner syndrome: A prospective cohort study.

In Scandinavian countries, programs for fertility preservation (FP) are offered free of charge at tertiary-care university hospitals to all patients facing infertility risks due to malignant diagnoses or benign conditions. In this prospective study we aimed to investigate trends and outcomes of FP indicated by a diagnosis of Turner syndrome. Prospective cohort study of patients with Turner karyotype receiving fertility preservation counselling at the Karolinska University Hospital between 1 January 1999 and 31 December 2021. The cohort included 100 women and girls that received counselling, whereof 27% were prepubertal girls, 59% were adolescents and 14% of adult age. Before 2006 all patients were referred for fertility counselling at the time of Turner diagnosis. Based on updated guidelines, mainly patients who showed signs of puberty were referred after 2006. As a result, spontaneous menarche was more common in the later period. In total, 39% of the cohort had monosomal karyotype (45X), 20% had 45X/46XX or 45X/47XXX mosaicisms and 36% had an X-chromosomal structural anomaly. Ovarian tissue cryopreservation was planned for 73% of all patients, and oocyte cryopreservation following gonadotropin stimulation was planned for 10% of the patients. Follicles were present in 25% of all biopsies analyzed. Adolescents were more likely to have follicles present (30%) than prepubertal girls (16%) or adult women (17%). The ten patients that underwent gonadotropin stimulation for oocyte cryopreservation underwent a total of 15 cycles and eight patients successfully preserved oocytes. In total, 26% of the cohort has undergone fertility treatment or expressed further interest in fertility preservation. Six women have given birth using donated oocytes and three following spontaneous conception. Two women have undergone re-transplantation of cryopreserved ovarian tissue, without regaining ovarian function, and none of the women that have cryopreserved oocytes has returned to use them. Fertility counselling for girls with Turner syndrome should ideally be offered at onset of spontaneous puberty to improve the chances of fertility preservation. Since the girls and women in this cohort are still young, the return rate and utilization of the preserved tissue and oocytes is expected to increase with time. ClinicalTrials.gov, identifier NTC04602962.

European Cancer Summit 2022 submission for Survivorship and Quality of Life NetworkFertility preservation and quality of life among adolescent and young adult cancer patients from across Europe

BACKGROUNDCompromised fertility in young people is one of the most life-altering late effect of cancer, affecting domains from sexuality and body image to self-esteem and quality of life (Logan and Anazodo 2019). While there exist evidence-based international guidelines for fertility preservation (FP) (Lambertini et al. 2020), there is no standardized way of implementing these guidelines within and between countries across Europe. We aimed to better understand young people’s awareness to FP and its relationship to QOL and mental health. METHODSIn this online cross-sectional study, adolescent and young adult (AYA) cancer patients and survivors from the wider European region responded to questions related to fertility preservation, awareness, access, and mental health and quality of life. Responses were summarized descriptively and organized by country clusters for meaningful between-cluster healthcare comparisons (Ferreira et al. 2018). Comparisons were done using χ2 or nested linear models Project and analyses were pre-registered at: https://osf.io/t9h82/. RESULTSParticipants were 629 cancer patients and survivors, aged 15 to 39 (M = 24.7 years) at diagnosis, recruited from 47 counties (26 EU) between February and August 2022. Overall, only 53% of respondents were made aware of the available medical options for fertility preservation. Country cluster comparisons revealed significant differences: compared to others, cluster Easter Countries A11Bulgaria, Hungary, Latvia, Lithuania, Romania, Slovakia showed that fewest people were informed about the possibility of infertility (χ2 (10, 629) = 17.21, p = 0.07). A multilevel linear model revealed that overall quality of life differed significantly between those who were aware of FP services within Southern and Eastern B country clusters22Southern countries are Cyprus, Greece, Italy, Malta, Portugal and Spain. Eastern B countries are Croatia, Czechia, Estonia, Poland, and Slovenia, see Ferreira et al. (2018). (t = 2.03, p = 0.425 and t = 2.30, p = 0.022; See Fig.1A). Specifically, 27% said fertility-related concerns greatly impacted their level of anxiety and depression, and 17% reported great impact on their quality of life (see Fig.1B). CONCLUSIONSSignificant cancer-related fertility inequalities exist among AYA cancer patients and survivors between countries and healthcare systems within Europe. Accessible FP programs should become an integral part of cancer rehabilitation for AYAs and should actively include them in the development of any novel guidelines. AYAs’ mental health and quality of life may be compromised by fertility-related distress and should be monitored throughout the cancer continuum.

Ethical Need for a Fertility Decision-Aid for Transgender Adults of Reproductive Age

Ethical Need for a Fertility Decision-Aid for Transgender Adults of Reproductive Age

Oocyte vitrification for fertility preservation following COS does not delay the initiation of neoadjuvant chemotherapy for breast cancer compared to IVM.

The objective of the present study was to evaluate whether oocyte vitrification following controlled ovarian stimulation (COS) for fertility preservation (FP) delays the initiation of neoadjuvant chemotherapy (NAC) for breast cancer (BC) as compared to in vitro maturation (IVM). We performed a retrospective cohort study including all BC patients eligible for oocyte vitrification following COS or in vitro maturation (IVM) before initiation of NAC between January 2016 and December 2020. The inclusion criteria were female patients aged between 18 and 40, with confirmed non metastatic BC, with indication of NAC, who have had oocyte retrieval for FP after COS, or IVM + / - cryopreservation of ovarian tissue (OTC). Various time points related to cancer diagnosis, FP, or chemotherapy were obtained from a medical record review. A total of 197 patients with confirmed BC who had oocyte retrieval following COS (n = 57) or IVM + / - OTC (n = 140) for FP prior to NAC were included. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COS or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36. 8 ± 13.5days; p = 0.89). The indication of NAC for BC should not be considered as an impediment to urgent COS for oocyte vitrification for FP.

Controlled Ovarian Stimulation Initiated at Different Phases of the Menstrual Cycle for Fertility Preservation in Oncological Patients: a Retrospective Study.

The purpose of this study is to compare conventional start in early follicular phase (EFP) with late follicular phase (LFP) and luteal phase (LP) in controlled ovarian stimulation (COS) for fertility preservation (FP) to assess differences in clinical outcomes. Retrospective study of the first cycles of COS for FP in oncological patients between 2012 and 2020 in a tertiary hospital. Two-hundred forty-eight cycles were classified into 3 groups: 176 cycles in EFP, 8 cycles in LFP, and 52 cycles in LP. Comparing LFP to EFP, there were no differences in number of oocytes (10.0 [6.3-16.0] vs 12.0 [8.0-18.0]; p = 0.253) or number of metaphase II (MII) obtained (7.0 [2.3-13.3] vs 9.0 [6.0-13.0]; p = 0.229). Total number of days needed was higher in LFP (14.5 [12.5-16.0] vs 3.0 vs 10.0 [8.3-11.0 p = 0.000) but without significant differences in number of days of usage of gonadotropins (11.5 [8.3-12.8] vs 10.0 [8.3-11.0] p = 0.308). No differences were found between LP and EFP in number of oocytes (14.5 [9.0-20.0] p = 0.151) or MII (11.5 [7.0-16.0] p = 0.084). Number of days of gonadotropins (11.0 [10.0-12.0] p = 0.00) and total dosing (3000.0 [2475.0-3600.0] p = 0.013) were significantly higher in LP. FORT and FOI were similar in all groups. COS with a random start in fertility preservation has similar outcomes to EFP start. Therefore, we can initiate COS at any phase of the menstrual cycle with optimal results. However, LP may need more days of stimulation.

Oncologists’ attitudes and practices regarding fertility preservation at a tertiary academic center.

190 Background: Infertility is a significant long-term consequence of cancer treatment and can negatively impact health related quality of life. As the incidence of cancer rises in younger populations and an increasing number of patients are prescribed systemic therapy in the neoadjuvant and adjuvant settings, the proportion of patients at risk for infertility will rise in tandem. Referrals for fertility preservation (FP), however, are low nationally and at our institution. Our study aimed to characterize oncologist attitudes and practices around FP and identify barriers to FP in patients with cancer. Methods: We developed a 21-item anonymous survey informed by literature review and input from FP stakeholders. The survey was distributed electronically to all faculty and fellows (n = 103) within our division of hematology/oncology during a division-wide conference on FP and subsequently emailed to all faculty and fellows, with three weekly follow up reminder emails. Results: 41 respondents completed the survey (response rate 40%), including faculty (46%) and fellows (39%). Respondents were predominantly male (49%), aged 25-40 (51%), white (44%), and non-Hispanic (73%). Most respondents agreed that FP should be offered to all patients with cancer receiving cytotoxic therapy (95%), however fewer respondents agreed that FP should be offered if it would cause a treatment delay by 2 weeks or more (63%). Respondents felt more comfortable counseling male patients (65%) than female patients (54%) and a larger proportion (41%) knew how to make referrals for sperm preservation (compared to 22% for oocyte preservation). The top barriers to counseling were patient past childbearing age (41%), provider did not remember to discuss (37%), and need for urgent treatment initiation (32%). The top barriers for an interested patient to undergo FP were perceived cost by patient (61%), need for urgent treatment initiation (59%), and patient was too overwhelmed to proceed with FP (42%). Conclusions: Oncologists agreed that FP is an important part of cancer care. However, many stated that cancer treatment initiation was often too time sensitive to counsel patients regarding fertility risks and make FP referrals. The FP referral process was not clear to many respondents. Clinic-level interventions are warranted to ensure timely patient access to FP. Based on the results of this study, we will launch a fellow-led Plan-Do-Study-Act Quality Improvement intervention to increase FP referrals in our clinics.

A FAILURE TO REACH DISADVANTAGED NEIGHBORHOODS: LEGISLATION IS NOT ENOUGH TO EXPAND ACCESS TO MEDICAL FERTILITY PRESERVATION

In 2019, IL made effective HB 2617 which mandated insurers provide coverage for fertility preservation (FP) services when medical treatment may cause iatrogenic infertility.1 IL is the only state nationwide to also extend coverage to publicly-insured recipients. Our study aimed to assess whether legislation mandating insurance coverage for medical fertility preservation (MFP) was associated with a change in the neighborhood socioeconomic disadvantage of patients accessing FP care.

FERTILITY PRESERVATION FOR NEWLY DIAGNOSED CANCER PATIENTS IN WEST AFRICA - A MULTI CENTERED OVERVIEW AMONG RELATED MEDICAL SPECIALISTS IN GHANA

Advances in medical oncology have improved cancer survival including childhood cancers. Fertility among cancer survivors is a major quality of life concern and potential fertility loss post cancer treatment has significant impact on patients’ psychosocial wellbeing. Availability and client referral for fertility preservation (FP) are key to giving cancer survivors some hope of future biological children. Data is scant on awareness and practice considerations among clinicians in developing countries.

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis

Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Relapse and disease-specific mortality after a diagnosis of BC. The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

P-484 Oocytes quality assessment in breast cancer: implications for fertility preservation

Abstract Study question Does the breast cancer (BC) influence the oocyte quality and ovarian response to controlled ovarian hyperstimulation (COH) for fertility preservation (FP) in female oncology patients? Summary answer The diagnosis of breast cancer does not seem to be associated with an impairment of ovarian reserve, but with a worsening of oocyte quality. What is known already Fertility preservation in female oncology patients should be integrated as part of management of cancer patient to improve their quality of life. Every day in Italy about 30 new cases of cancer are diagnosed in patients with age under 40 years and BC is the most common malignancy in women undergoing fertility preservation. Currently mature oocyte cryopreservation is a standard technique for fertility. The studies on the outcome of ovarian response after ovarian stimulation in specific cancer patients are limited. Only few reports have suggested a deleterious impact of the oncological disease on quality of follicular growth and ovarian function. Study design, size, duration This is a retrospective single-center case-control study carried out in the IVF (in vitro fertilization) Unit at the Sandro Pertini Hospital in Rome between 2016 and 2021. The aim of this study is to investigate the effect of BC on number, above all on quality of oocyte and on dysmorphic oocyte ratio, in oncology patients compared to women age- and date-matched controls undergoing COH for IVF for male or tubal factor infertility. Participants/materials, setting, methods A total of 294 women were enrolled in the study: 105 women affected by breast cancer in the case group and 189 healthy women in the control group. Boths groups were comparable in terms of age, body mass index (BMI) and antimulleran hormone (AMH) value, E2 level at triggering day, total FSH cumulative dose, stage, histotype, BRCA status and hormone receptors. The primary outcome was number and quality of retrievd oocyte from ovarian pick-up (OPU). Main results and the role of chance There were no significant differences in terms of basal fertility indices between the 2 groups: median AMH levels were 2.3 ng/mL in BC patients and 2.8 ng/mL in control group (p = 0.103). The median length of stimulation was 11 days in both groups. The median of total immature oocytes (oocytes MI + germinal vesicle) was 2 in cancer patients and 0 in control group (p &amp;lt; 0.0001). Finally, the median of total dysmorphic oocytes were 1 in cancer group vs 0 (p &amp;lt; 0.0001). The multivariable analysis identified the cancer as risk factors of presence of dysmorphic oocytes (OR (95%CI):3.92 (1.84-8.35). Moreover either in the case and control group age, BMI, AMH, duration of stimulation, E2 level at triggering day, total FSH cumulative dose and, only for BC patients, stage, histotype, BRCA status and hormone receptors were not statistical significantly associated with the presence of dysmophic oocytes. Finally, our data confirmed that the cancer is the only risk factors not only for the presence of dysmorphic oocytes, but also respect to the number of dysmorphic oocytes and to the percentage of dysmorphic oocytes respect to the total number of retrieved oocytes for patient. Two patients have had a spontaneous pregnancy. Limitations, reasons for caution The limitations concern the paucity of specific cancer group especially BRCA mutated BC patients and the different triggers for induction of final maturation. We still have not a follow up data to evaluate the competence of vitrified MII oocytes for oncology patients and we cannot report information on spontaneous births. Wider implications of the findings The BC diagnosis is a four times greater risk factor in retrieving dysmorphic oocytes, but the stage of BC does not influence the number of retrieved dysmorphic oocytes. Further studies are necessary to evaluate the etiopathogenetic mechanisms underlying oocyte abnormalities in specific group of female oncology patients. Trial registration number 0104898/2020

P-464 Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy

Abstract Study question Is long-acting GnRH agonist (GnRHa) trigger an efficacious and safe option in oocyte cryopreservation cycles before chemotherapy, when ovarian suppression is planned? Summary answer The flare-up effect of long-acting GnRHa is able to induce the final oocytes’ maturation and subsequently suppress ovarian function for chemotherapy What is known already When both oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRHa are accepted by the patient for fertility preservation (FP), the first injection of GnRHa is administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. Some cases of ovarian hyperstimulation (OHSS) have been described in this setting, as a consequence of the initial flare-up effect on recently stimulated ovaries. The subsequent risks (including a possible delay in the start of chemotherapy) may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. Study design, size, duration Prospectively collected data from 75 oncological patients who underwent ovarian stimulation for oocyte cryopreservation from 2016 to 2021 were evaluated. From 2020 all patients for whom ovarian suppression after cryopreservation was planned were offered long-acting GnRHa trigger. All other patients were enrolled as controls, stratified for triggering method used (highly purified Chorionic Gonadotrophin 10000 UI or short acting GnRHa 0.2 mg). Participants/materials, setting, methods All the ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single tertiary level public fertility centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. Results were compared by Mann-Whitney U test or Chi-Square test, as appropriate. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Main results and the role of chance After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, 13 women received the long-acting GnRHa trigger (Triptorelin 3.75 mg. Group A) 36 hours before oocyte retrieval, 37 women received highly purified Chorionic Gonadotrophin 10000 UI (Group B) and 25 women the short-acting GnRHa (Triptorelin 0.2 mg. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 11 (range 7-18) with a maturation rate of 80% (68-100), 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 12 (0-34), 79% (50-100) in group C (no statistically significative difference). There was no case of OHSS in Group A. One patient in group B and one in group C developed OHSS after administration of long-acting GnRH in the luteal phase after COS (five days after oocytes retrieval). Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.29 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Limitations, reasons for caution We are aware that our data should be confirmed by more robust randomized studies and higher numbers. Wider implications of the findings We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and in guaranteeing complete suppression by chemotherapy initiation. The feasibility of this strategy is an important step in reducing the risk of OHSS, giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy. Trial registration number not applicable

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

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