Undergoing Fertility Preservation Research Articles

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

O-086 Risk of serious adverse event after fertility preservation procedures: a comparison of cancer and non-cancer patients

Abstract Study question Do cancer patients have a higher risk of serious adverse event associated to fertility preservation procedures compared to non-cancer patients ? Summary answer No increased risk of adverse event after fertility preservation procedures was identified in cancer patients compared to non-cancer patients undergoing fertility preservation for other indications. What is known already Current recommendations encourage a prompt and exhaustive discussion on the different techniques of fertility preservation that can be performed in cancer patients of reproductive age prior to cancer treatments. Although cryopreservation of mature oocytes and/or embryos is the technique of reference in the absence of contraindication, ovarian stimulation and subsequent oocyte retrieval are associated to complications. Cancer patients might present an additional risk given tumoral hypervascularity and proinflammatory environment, as well as possible immune or coagulation disorders. However, whether cancer patients have an increased risk of serious adverse event associated to fertility preservation procedures compared to non-cancer patients remains unknown. Study design, size, duration A bicentric, retrospective study between January 1st, 2014 and December 31st, 2021. Participants/materials, setting, methods All women undergoing fertility preservation procedures by oocyte and/or embryo cryopreservation after controlled ovarian stimulation or in vitro maturation.The main endpoint was the occurrence of a serious adverse event (hospitalization for ovarian hyperstimulation syndrome, hemorrhage, infection, thromboembolic event, ovarian torsion, acute urine retention or death) in cancer patients compared to non-cancer patients undergoing fertility procedures. Main results and the role of chance A total of 4476 cycles (n = 3180 patients) were included, of which 3761 after controlled ovarian stimulation and 715 in vitro maturation cycles. Among the 4476 cycles, 1678 were performed in an oncological context (n = 1546 cancer patients) and 2798 were fertility preservation cycles for an indication other than cancer (n = 1634 patients). A total of 29 serious adverse events associated to fertility preservation procedures were registered, of which 17 intraperitoneal hemorrhages, 8 cases of ovarian hyperstimulation syndrome, 3 cases of infection and 1 case of acute urine retention. The risk of serious adverse event associated to fertility preservation procedures was not significantly different between cancer patients and non-cancer patients (0.36% vs. 0.82%, respectively, P = 0.06). Young age (P = 0.002), a higher number of oocytes retrieved (P = 0.006) and a higher number of oocytes vitrified (P = 0.002) were significantly associated to the risk of presenting a serious adverse event after fertility preservation. Limitations, reasons for caution Although rates of serious adverse events in our study are similar to that reported in previous literature and that the declaration and registration of any serious adverse event is mandatory according to French legislation, it is possible that not all serious adverse events were declared and registered. Wider implications of the findings Given the trend of delaying parenthood and the improved survival rates after cancer treatments, these findings are of particular importance, emphasizing the safety of performing fertility preservation procedures for cancer patients of reproductive age who might have a pregnancy desire after cancer treatment. Trial registration number not applicable

P-356 Fertility preservation for patients with breast cancer: altered response to ovarian stimulation and loss of cholesterol homeostasis in ovarian follicles

Abstract Study question Does the presence of breast cancer alter the ovarian response to hormonal stimulation and the cholesterol homeostasis in ovarian follicles? Summary answer The deleterious impact of breast cancer on the ovarian response might be link to an alteration of the cholesterol biosynthesis in cumulus cells. What is known already Breast cancer is the most frequent cancer in reproductive-aged women. The cancer itself seems to exert a deleterious impact on the ovarian functions. Indeed, cancer patients who undergo fertility preservation before cancer therapy initiation show a poorer response to ovarian stimulation than healthy women. Nevertheless, this impact remains controversial, and the mechanisms by which the cancer impairs the ovarian functions are poorly understood. To our knowledge, no study has yet evaluated the impact of breast cancer on the cholesterol biosynthesis pathway in human cumulus cells, a pathway essential for oocyte competence to maturation and fertilization. Study design, size, duration 30 patients with breast cancer (10 triple negative (TNBC), 10 hormone-receptor positive (HR+) and 10 HER2 positive (HER2+)) and 30 women oocytes donors undergoing oocyte cryopreservation will be included from January 2019. We assess ovarian response to stimulation (number, quality of retrieved oocytes; total FSH dose). We quantify the level of enzymes and regulators of the cholesterol biosynthesis pathway in cumulus cells (CC) by RT-qPCR. We plan to quantify cholesterol levels in follicular fluids (FF). Participants/materials, setting, methods Since January 2019, 25 breast cancer patients (9 TNBC, 8 HR+ and 8 HER2+) and 30 oocytes donors (control group) under 37 years old have been included. Ovarian stimulation was performed with antagonist protocol. Following ovarian pick up and denudation, CC and FF were collected. After total RNAs extraction from CC, the expression levels of enzymes and regulators of the cholesterol biosynthesis pathway were quantified by RT-qPCR. Cholesterol levels will be quantified in FF. Main results and the role of chance The clinico-biological characteristics (age, BMI) are comparable between cancer patients and the control group (p > 0.05). Serum AMH levels are lower in the TNBC subgroup (2.3±1.6 ng/mL) than in the control group (4.7±2.8 ng/mL, p = 0.04). A poorer ovarian response to ovarian stimulation is observed in the breast cancer group compared with the control group (number of mature oocytes: 9.4±5.2 vs. 14.5±7.7, p = 0.007). Among the cancer patients group, the TNBC subgroup shows the poorest ovarian response to stimulation (number of mature oocytes: 7.6±4.3 vs. 14.5±7.7 in control group, p = 0.006) despite the highest total administered FSH dose (2480±880 IU vs. 1831±460 IU in control group, p = 0.02). Dysregulation of the cholesterol biosynthesis pathway is observed in the breast cancer group. For TNBC and HR+ cancer patients, we observed an increase in the transcripts levels of CYP51 enzyme (respectively 3.28±1.69 vs. 1.84±2.33, p = 0.0098 and 1.77±1.78 vs. 1.84±2.33, p = 0.03) and SREBP2 activator (respectively 2.04±0.95 vs. 1.27±1.13, p = 0.003 and 1.12±0.47 vs. 1.27±1.13, p = 0.02) of the cholesterol biosynthesis pathway compared to the control group. In HER2+ cancer patients, a significant decrease in the expression levels of SQLE (0.39±0.34 vs 1.81±3.99, p = 0.001) and DHRC7 enzymes (0.33±0.32 vs 1.21±0.88, p = 0.0002) is observed compared to the control group. Limitations, reasons for caution Our preliminary results should be confirmed with the analysis of a larger number of participants. We should confirm that the observed modulations in the expression levels of enzymes and regulators of the cholesterol biosynthesis pathway led to a loss of cholesterol homeostasis by quantifying cholesterol in FF. Wider implications of the findings Our findings strengthen the hypothesis that cancer exerts a deleterious impact on the ovarian functions, as we observed a lower ovarian response in patients with breast cancer. This project will have clinical implications, such as to adapt the fertility preservation approach according to the breast cancer subtype. Trial registration number Not applicable

P-673 Tubulointerstitial nephritis antigen-like 1 (TINAGL1) expression is lower in the follicular fluid of patients with diminished ovarian reserve (DOR): A novel biomarker

Abstract Study question Are TINAGL1 levels in follicular fluid associated with ovarian reserve in patients undergoing ovarian stimulation for in-vitro fertilization (IVF)? Summary answer TINAGL1 concentration was lower in the follicular fluid (FF) of patients with DOR vs patients without infertility or polycystic ovarian syndrome (PCOS). What is known already TINAGL1 is an extracellular matrix protein involved in cell adhesion, proliferation, migration, and differentiation. TINAGL1 has previously been shown to be expressed in the mouse ovary and to be a serum biomarker that varies throughout the mouse estrous cycle, peaking in the estrous phase. Furthermore, TINAGL1 knockout mice have been shown to be infertile. TINAGL1 expression in the human ovary has not been previously evaluated. Study design, size, duration Between 2019 and 2023, a prospective study of 136 patients undergoing ovarian stimulation and oocyte retrieval (OR) was conducted at a single academic fertility center to assess TINAGL1 levels in luteinized FF and granulosa cells. Study groups were determined by infertility diagnosis: DOR n = 24, polycystic ovary syndrome (PCOS) n = 27, and control n = 85 (undergoing fertility preservation or had a partner with male factor only). Participants/materials, setting, methods TINAGL1 protein levels were quantified in the FF of patients that underwent OR via commercial enzyme-linked immunosorbent assay (ELISA). Granulosa cells were recovered from FF after OR, underwent lysis, RNA extraction, cDNA amplification and TINAGL1 mRNA expression was quantified via quantitative real-time polymerase chain reaction (qPCR). Demographics and infertility diagnoses were collected from the medical record. TINAGL1 levels were compared between the three groups. Statistical analysis was performed with parametric and non-parametric tests as appropriate. Main results and the role of chance Patients with DOR were younger when compared to the control and the PCOS group [Mean(SD) 32.7 (3.8) vs 34.45(3.9) vs 37.7 (3.0) years, p < 0.001] and had lower AMH levels [1.19 (0.8) vs 3.96 (3.03) vs 8.67 (4.56) ng/ml, p < 0.001]. TINAGL1 protein concentration in FF was measured by ELISA. Mean (SD) TINAGL1 levels were highest in PCOS, and lowest in the DOR group. Mean TINAGL1 levels were higher in the FF of the PCOS group when compared to the control group [4.73(7.15) vs 4.45 (4.57) ng/ml, p = 0.83] but this difference did not reach statistical significance. However, mean TINAGL1 FF levels were significantly lower in the DOR group when compared to the control group [2.54 (1.6) vs 4.48 (4.57) ng/ml, p = 0.04]. TINAGL1 was also found to be expressed in the granulosa cells with qPCR. TINAGL1 expression was upregulated by (+89%) in the PCOS group vs the control group (p = 0.0095). Importantly, there was a trend for decreased (-52%) TINAGL1 expression in DOR when compared to the control group (p = 0.67). The latter result should be interpreted with caution since only a subset of samples had sufficient granulosa cells for RNA extraction (DOR=4, control=18, PCOS=5). Limitations, reasons for caution This is a single institution study with a small number of patients in the DOR group (n = 24). Wider implications of the findings This is the first study to show that TINAGL1 is expressed in human granulosa cells. Decreased TINAGL1 may be a biomarker associated with DOR. Future studies should assess serum TINAGL1 levels at baseline and during ovarian stimulation and its contribution to the pathophysiology of DOR. Trial registration number Not applicable

P-665 High FSH level impairs VEGF secretion by thawed human ovarian tissue

Abstract Study question How does a high FSH level as related to POI (premature ovarian insufficiency) affect VEGF secretion by thawed human ovarian tissue? Summary answer After thawing, the high FSH concentration of 175mIU/mL (10ng/mL) significantly decreased VEGF secretion by human ovarian tissue by 25.6%. 17.5mIU/mL did not change VEGF secretion. What is known already Cryopreservation of ovarian cortical tissue has become an important method in fertility preservation. However, 70% of the follicles do not survive the reimplantation process due to an insufficient blood supply and oxidative stress. Human ovarian tissue secretes angiogenic factors, including VEGF, spontaneously. Its regulation by FSH is not known although 50% of the reimplantation patients show increased FSH levels (>25mIU/mL) due to POI. Study design, size, duration Provided a signed consent, biopsy punches of ovarian cortical tissue from 8 patients undergoing fertility preservation were studied. Slow freezing and thawing was applied as in the intern routine instructions. Participants/materials, setting, methods Human ovarian cortical tissue was cultured in full medium at 37 °C for 48h after thawing in presence or absence of 17.5mIU/mL (1ng/mL) or 175mIU/mL (10ng/mL) recombinant human FSH. VEGF-A secretion was measured by ELISA. The expression of VEGF-A, HIF-1α and FSHR was assessed by immunohistofluorescence per follicle. The effect of FSH was assessed by one-way-ANOVA with Tukey’s post test. The effect of culture or follicular maturation stage was analyzed by t test. Main results and the role of chance After thawing, VEGF secretion recovers and rises over time. The addition of 175mIU/mL FSH significantly impaired VEGF-A expression compared to untreated ovarian tissue (p = 0.016). The analysis of 481 follicles showed similar results of FSH affecting VEGF-A expression by immunostaining. In particular, primordial follicles expressed significantly less VEGF-A compared to growing follicles (primary+secondary; p < 0.0001). 48h tissue culture significantly increased VEGF-A expression in primordial follicles (p = 0.0041). The addition of the high FSH level significantly decreased VEGF-A expression in growing follicles (p = 0.0005). Limitations, reasons for caution Although VEGF-A is a key factor in angiogenesis, more factors are known to affect angiogenesis. The direct effect on angiogenesis should be evaluated. Moreover, the conditions in tissue culture may not represent those after reimplantation. Wider implications of the findings High FSH levels, as seen in patients with POI, might impair ovarian VEGF expression and angiogenesis. Hormone replacement therapy (HRT) might be endorsed before and during ovarian tissue reimplantation. More clinical and biological data are required to understand the regulators of angiogenesis after ovarian tissue reimplantation adequately. Trial registration number not applicable

Cancer Therapy, Gonadal Function, and Fertility Preservation: Narrative Review.

Fertility preservation was designed to help young patients overcome complications of cancer treatments, but its effectiveness is unknown. We sought to investigate how often patients with cancer are offered fertility preservation and if patients offered fertility preservation are more likely to have offspring. We searched Embase (through 2022) and PubMed (through 2022). Our broad computerized search strategy was built upon using the keywords "chemotherapy," "radiation," and "fertility." The search took place on December 1, 2022. We included randomized and observational studies and excluded reviews and case reports/series. Eighty-five articles that answered at least one of the research questions were included. Studies assessing fertoprotective therapies often rely on surrogate markers for fertility. Multiple factors affect these markers of fertility. The median premature ovarian failure rate among the intervention group was 18% (IQR, 12%-20%), and among the control group, it was 25% (IQR, 19%-33%). Five of 11 studies reported a significant benefit from fertoprotective therapy. Pregnancies occurred in a median of 21% (IQR, 6%-52%) of patients in the intervention group and 11% (IQR, 7-44) of patients in the control group, with three of seven studies reporting a higher percentage of pregnancies among the intervention group. We reviewed the literature on several questions surrounding fertility preservation and found that there is limited and low-quality research on these therapies in cancer. Hence, there is a strong need for studies, especially randomized studies, that follow patients with cancer who undergo fertility preservation and assess outcomes in which patients are most interested.

Global status of research on fertility preservation in male patients with cancer: A bibliometric and visual analysis

BackgroundRecently, male fertility preservation before cancer treatment has become more prevalent. The research in this field has progressed over time, with some studies having a major impact and providing guidance for further research. However, the trends and hotspots of research on fertility preservation in male cancer patients may have changed; exploring them is essential for relevant research progress. DesignWe extracted relevant studies from the Web of Science Core Collection database, capturing information on the countries of study, affiliations, authors, keywords, as well as co-citations of references and journals. To identify publication trends, research strengths, key subjects, prominent topics, and emerging areas, we conducted a bibliometric analysis using CiteSpace. ResultsWe included 3201 articles on fertility preservation in male cancer patients published over January 1999 to December 2023 were included. Although the relevant research growth rate was slow initially, the number of publications increased annually. Of all study countries, the United States, Germany, and Japan reported the earliest studies; the United States published the highest number of relevant studies. The US institutions remained at the forefront for all 25 years, and the US researcher Ashok Agarwal published the most articles. Literature co-citation analyses indicated a transformation in the study participants; they comprised a younger demographic (i.e., a large number of adolescent male patients underwent fertility preservation); moreover, fertility preservation techniques evolved from sperm cryopreservation to testicular tissue cryopreservation. Research on reproductive outcomes of sperm cryopreservation was the recent hotspot in male fertility preservation research, and the impact of immunotherapy and checkpoint inhibitors on male fertility requires further research. ConclusionsMale fertility preservation will be a major future research focus, with closer connections and collaborations between countries and organizations. Our results present the historical data on the development of research on male fertility preservation in cancer patients, providing relevant insights for future research and development in this study area.

Fertility among young breast cancer survivors attempting pregnancy: A prospective, multicentre cohort study.

1518 Background: Despite high interest among young women diagnosed with breast cancer (BC) in future fertility, prior research has been hampered by short follow-up and lack of prospective assessment of pregnancy attempts. We sought to describe fertility outcomes among young women participating in a prospective cohort who reported pregnancy attempt post-BC diagnosis. Methods: Women with stage 0-III BC in the Young Women's Breast Cancer Study (YWS, NCT01468246), a multicenter, prospective cohort of women diagnosed at age ≤40 from 2006-2016 who reported attempting pregnancy post-diagnosis were included. Those with prior hysterectomy, bilateral oophorectomy, or metastatic disease at diagnosis were excluded. Data on attempting pregnancy and fertility outcomes were obtained from serial surveys. Multivariable logistic regression with stepwise model selection was used to identify factors associated with pregnancy and live birth. Results: Among 1213 eligible participants, 197 reported any attempt of pregnancy (16%) over a median follow-up of 11 years (range: 3-17). Among attempters, median age at diagnosis was 32 years (range: 17-40); 74% were non-Hispanic White; 41% had stage I, 35% stage II, 10% stage III, and 14% stage 0 BC; 76% had HR+ disease; 68% received chemotherapy; 57% received endocrine therapy within one year post-diagnosis; 13% were BRCA1/2 pathogenic variant (PV) carriers; 51% reported financial comfort at baseline; 51% were nulligravida and 72% nulliparous at diagnosis; 28% had undergone fertility preservation consisting of egg/embryo freezing at diagnosis; 15% reported a history of infertility before BC diagnosis. Most (73%) reported ≥1 pregnancy after diagnosis and 65% reported ≥1 live birth. Median time from diagnosis to first pregnancy was 48 months (range: 6-125). In the multivariable model, greater age at diagnosis (odds ratio [OR] 0.82 per year increase, 95% CI 0.74-0.90, P<0.0001) was negatively associated with pregnancy, while financial comfort at baseline (OR 2.04, 95% CI 1.01-4.12, P=0.047) was predictive of pregnancy. For live births, greater age at diagnosis was negatively associated (OR 0.82 per year increase, CI 95% 0.76-0.90, P<0.0001) while having undergone fertility preservation at diagnosis was predictive (OR 2.78, 95% CI 1.29-6.00, P=0.009). History of infertility, nulliparity at diagnosis, tumor characteristics, cancer treatment, race, ethnicity, and BRCA1/2 PV status were not associated with either outcome. Conclusions: This is the first prospective study with greater than 10 years of follow-up to report fertility outcomes in young BC survivors accounting for attempting pregnancy. The majority achieved a pregnancy and most reported a live birth. Our findings can be incorporated into the counseling of young BC patients and survivors, and highlight the need for accessibility of fertility preservation services for this population. Clinical trial information: NCT01468246 .

A case report of recurrent ovarian torsion following oocyte cryopreservation managed with dual technique oophoropexy

Introduction: Ovarian torsion is a known risk of ovarian hyperstimulation done as part of fertility treatments. The purpose of this case report is to describe an unusual case of recurrent ovarian torsion following oocyte cryopreservation that was ultimately managed with ovarian detorsion and dual technique oophoropexy. Case Report: The patient presented is a 25-yearold female with history of recurrent ovarian torsion who underwent fertility preservation with ovarian cryopreservation in the setting of risk for ovarian loss in the case of recurrent torsion episodes. Following ovarian hyperstimulation and oocyte retrieval, the patient experienced three recurrent episodes of torsion which were surgically managed. On the third episode, a dual technique oophoropexy was performed using both utero-ovarian ligament plication and ovarian fixation. Conclusion: This case describes an unusual presentation of an uncommon complication of ovarian stimulation. During her surgical management of recurrent ovarian torsion, ovarian conservation was prioritized and a dual oophoropexy technique was utilized which has thus far prevented further recurrent episodes of torsion.

Oocyte retrieval in social fertility preservation: challenging traditional beliefs on gonadotropin dosing and follicular size.

To investigate treatment approaches for fertility preservation patients, with a focus on timing of oocyte retrieval, and to determine whether their characteristics differ from those of other IVF patients. Additionally, to evaluate the significance of follicle size on triggering day in the context of fertility preservation. This retrospective cohort study was conducted in a tertiary, university-affiliated medical center. It compared 140 matched patients undergoing social fertility preservation to 140 patients undergoing IVF treatment due to male factor infertility. Patients undergoing fertility preservation received a higher initial gonadotropin dose and had more oocytes retrieved than the control group. Within the fertility preservation cohort, a negative correlation was observed between the rate of large follicles and the number of retrieved oocytes. While there was no significant association between rate of large follicles and oocyte maturation rate in the entire group, age-stratified analysis revealed a negative relationship. Analysis revealed that although traditional treatment determinants such as follicular size and gonadotropin dosing were considered, peak estradiol levels were consistently identified as significant predictors of treatment outcomes. Physicians may modify treatments for fertility preservation, emphasizing a higher gonadotropin dosage to maximize oocyte retrieval. Elevated estradiol levels can serve as a real-time predictive marker for the number of mature oocytes. While treatment strategies can influence outcomes, intrinsic patient factors, particularly baseline ovarian function, remain crucial. These results challenge beliefs regarding the importance of larger follicles and suggest the need for a tailored approach, considering patient age and specific fertility preservation objectives.

Abstract PO4-11-11: Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation

Abstract Background: Fertility preservation and family planning are pressing survivorship concerns for many young, reproductive-aged women with hormone receptor-positive (HR+) early-stage breast cancer. Following primary treatment, patients typically receive 5-10 years of adjuvant endocrine therapy (ET), during which pregnancy is contraindicated and fertility may decrease. The first-of-its-kind POSITIVE trial (NCT02308085) sought to challenge this archetype by prospectively evaluating the impact of temporary ET interruption to allow patients to attempt conception. Participants (n=516) received 18-30 months of ET followed by a 3-month washout period prior to initiating a 2-year break from therapy to attempt pregnancy. Results demonstrated that short-term disease outcomes were not impacted by temporarily pausing therapy to allow women who desire conception to attempt pregnancy. This survey-based study aimed to evaluate community oncologists’ perceptions of the POSITIVE trial data, ET interruption, and fertility preservation efforts. Methods: US-based oncologists convened at three live meetings in March and April 2023 to review clinical updates presented at SABCS 2022. Participant characteristics and demographic data were collected via an online survey prior to the respective meetings. Perceptions/reactions to clinical updates were captured using audience response system technology. Data were summarized using descriptive statistics. Results: Among 157 respondents, 82.8% identified as community providers, with 17.9 mean years of clinical experience. On average, participants reported that 85.4% of their time is allocated towards direct patient care, with approximately 21 patients seen per clinic day. Most respondents (85.8%) indicated that they only refer patients to a fertility specialist if the patient initiates fertility preservation discussions and nearly half (45.7%) reported that within the last year, 20% or less of their patients have discussed fertility concerns with them prior to initiating therapy. Additionally, over three-quarters of respondents (79.9%) indicated that 10% or less of their patients with breast cancer underwent fertility preservation within the last year. Prior to reviewing the POSITIVE trial data, 51.3% of respondents reported that they would be most likely to offer therapy interruption to patients with low- or intermediate-risk disease, while 19.8% would do so for all patients regardless of risk status. After reviewing the POSITIVE trial data, 59.3% of respondents would offer therapy interruption to patients with low- or intermediate-risk disease, while 30% would do so for all patients regardless of risk status. Notably, a majority of respondents (54.8%) indicated that they would recommend a therapy interruption of 12 months or less, while 11.1% would opt for 19-24 months. Conclusions: Findings demonstrate that the onus of initiating discussions surrounding fertility and reproductive topics is often placed on patients, and many patients do not proactively address these matters or undergo fertility preservation prior to initiating treatment. Overall, respondents viewed the POSITIVE trial favorably, as evidenced by their increased willingness to consider temporary ET interruption for all patients following their review of the study data. Although the POSITIVE trial allowed up to 2 years of therapy interruption, respondents preferred a treatment break of 12 months or less. With the adoption of the POSITIVE strategy into routine clinical practice, younger women with HR+ breast cancer may no longer be faced with the difficult choice of pursuing potentially life-saving therapy or starting/expanding a family, thereby addressing a current unmet survivorship need among this patient population. However, it remains to be seen how many physicians will offer this approach, who is the ideal candidate, and what the appropriate ET interruption length will be. Citation Format: Brooke Leon, Robert Bone, Yolaine Jeune-Smith, Sigrun Hallmeyer, Bruce Feinberg. Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation [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 PO4-11-11.

Ovarian reserve in patients with FMR1 gene premutation and the role of fertility preservation

IntroductionWomen with premutation (PM) of the FMR1 gene may suffer from reduced ovarian reserve or even premature ovarian insufficiency (POI). We studied hormonal and ultrasound ovarian reserve, fertility and fertility preservation outcomes in these patients. Patients and methodRetrospective cohort study of 63 female FMR1 premutation carriers. ResultsSixty-three female patients bearing an FMR1 premutation were included. Median age was 30 years [26.5–35]. Median number of CGG triplets was 83 [77.2–92]. Before diagnosis of PM, 19 women (30%) had had in all 35 pregnancies, resulting in 20 births, including 7 affected children. After diagnosis of PM, 17 women (26.1%) had in all 23 pregnancies, at a median age of 34.5 years [32.2–36.0]: 2 after pre-implantation genetic diagnosis, 3 after oocyte donation, 18 spontaneously, and 5 ending in medical termination for fragile X syndrome. Thirty-three patients (52.4%) had POI diagnosis (median age, 30 years [27–34]) with median FSH level 84 IU/L [50.5–110] and median AMH level 0.08ng/mL [0.01–0.19]. After POI diagnosis, 8 women had in all 9 pregnancies: 3 following oocyte donation, and 6 spontaneous in 5 women (15.1%). Eight of the 9 pregnancies resulted in a live birth (including 2 affected children) and 1 in medical termination for trisomy 13. The median age of the 30 patients without POI was 31 years [25.2–35.0].Thirteen women (20.6%) underwent fertility preservation, at a median age of 29 years [24–33]: FSH 7.7 IU/L [6.8–9.9], AMH 1.1ng/mL [0.95–2.1], antral follicle count 9.5 [7.7–14.7]. A median 15 oocytes [10–26] were cryopreserved in a median 2 cycles [1–3]. At the time of writing, no oocytes had yet been thawed for in-vitro fertilization. ConclusionsThis study shows the importance of early fertility preservation after diagnosis of FMR1 premutation in women, due to early deterioration of ovarian reserve. Genetic counseling is essential in these patients, as spontaneous pregnancies are not uncommon, even in cases of impaired ovarian reserve, and can lead to birth of affected children.

Pain after oocyte retrieval in women with endometriosis undergoing fertility preservation or IVF

Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF? This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS). Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; P < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m2 versus 24.6 ± 4.4 kg/m2; P < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; P = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; P = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, P < 0.001; 16% versus 25%, P = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; P = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06-5.15; P = 0.039). Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result.

Gonadotropin-Releasing Hormone (GnRH) Agonists Do Not Protect Ovarian Function in Patients Undergoing Stem Cell Transplants.

Introduction Medical indications for fertility preservation include any malignancy, chronic illness, or disease that would require gonadotoxic chemotherapy or radiation (conditioning regimens), which would impede a woman's ability to conceive in the future. Thus, any patient who plans to undergo a gonadotoxic regimen is advised to cryopreserve oocytes or embryos, which can be used in the future at the patient's convenience. Attempts have been made to suppress ovarian function with gonadotropin-releasing hormone agonists (GnRH-a) to induce ovarian quiescence and, thereby, theoretically limit the gonadotoxicimpact onthe follicular pool. We explored the use of leuprolide (a type of GnRH-a) inpreventing primary ovarian insufficiency (POI) in a cohort study of patients who underwent hematopoietic stem cell transplants (HSCT) at the National Institutes of Health(NIH); since the conditioning regimens for HSCT include cyclophosphamide and other gonadotoxic therapies, we hypothesized that GnRH-a would be ineffective in preventing POI. Methods We assessedpatients who underwent fertility preservation prior to their stem cell transplant, as their follicular-stimulating hormone(FSH) levels were evaluated prior to and post-chemotherapy. Twenty-nine patients who underwent hormonal evaluation prior to and post-chemotherapy were included. The control group did not receive GnRH-a prior to chemotherapy, while the treatment group did receive GnRH-a pre-chemotherapy. Results Our data revealed that 80% of the control group had menopausal levels post-chemotherapy, while 91% of the treatment group still had menopausal levels post-chemotherapy (p=0.33). Conclusions Thus, our hypothesis that GnRH-a is ineffective in reducing the risk of POI in a cohort of patients who receive conditioning regimens for HSCT was confirmed.

Fertility outcomes several years after urgent fertility preservation for breast cancer patients

To study the fertility outcomes of women who tried to conceive after breast cancer treatment and fertility preservation. Retrospective observational, bicentric cohort study. All patients who had undergone fertility preservation before breast cancer treatment between January 2013, and July 2019 were included (n=844). The end-point date was March 1, 2022. Patients with missing data on pregnancy attempts after cancer diagnosis (n=195) were excluded from the pregnancy analysis. Cumulative incidences of pregnancy and live birth were calculated. For women who became pregnant, the time to conception was calculated between the first fertility preservation consultation and the estimated day of conception. For those who did not conceive, we considered the time between first fertility preservation consultation and the end-point date or the date of patient death. A Cox regression model was used to study the predictive factors of pregnancy and live birth. Among the 649 patients with available data on pregnancy attempts after breast cancer diagnosis, 255 (39.3% [35.5-43.2]) tried to conceive (median follow-up 6.5 years). Overall, 135 (52.9% [46.6-59.2]) of these patients achieved a pregnancy, mainly through unassisted conception (79.3% [72.8-84.8]), and 99 reported a live birth (representing 38.8% of patients who attempted conception). In our cohort, 48 months after the first fertility preservation consultation, the cumulative incidence of pregnancy was 33.1% ([27.6-37.9]). After adjustment for age, parity, type of chemotherapy administration and endocrine therapy, only multiparity at diagnosis and absence of chemotherapy were positive predictive factors of pregnancy after cancer. Of the 793 patients who had vitrified oocytes/embryos, 68 used them (27% [21.3-32.5] of the patients who tried to conceive), resulting in 8 live births (11.8% [5.2-21.9]). Women who used their cryopreserved oocytes/embryos were older at the first consultation of fertility preservation (HR 1.71(1.42-2.21)), and chose more often to vitrify embryos (HR 1.76(1.28-2.23). Although pregnancy rates after fertility preservation for breast cancer are low, most conceptions are achieved without medical assistance. Our findings provide useful information to advise women on the different techniques of fertility preservation, their efficacy and safety, as well as the relatively high chances of unassisted conception.

Evaluation of the Gonadotoxicity of Cancer Therapies to Improve Counseling of Patients About Fertility and Fertility Preservation Measures: Protocol for a Retrospective Systematic Data Analysis and a Prospective Cohort Study.

Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might be required. However, as detailed data about the necessity to perform fertility preservation treatment are very limited, this study was designed to fill this data gap. Primary objective of this study is to analyze the impact of cancer therapies and chemotherapies on the ovarian reserve and sperm quality. Secondary objectives are to analyze the (1) impact of cancer therapies and chemotherapies on other fertility parameters and (2) probability of undergoing fertility preservation treatments in relation to specific cancer diseases and treatment protocols and the probability to use the frozen gametes and gonadal tissue to achieve pregnancies. First, previously published studies on the gonadotoxicity of chemo- and radiotherapies among patients with cancer will be systematically analyzed. Second, a prospective cohort study set up by approximately 70 centers in Germany, Switzerland, and Austria will collect the following data: ovarian function by analyzing anti-Müllerian hormone (AMH) concentrations and testicular function by analyzing sperm parameters and total testosterone immediately before and around 1 year after gonadotoxic therapies (short-term fertility). A follow-up of these fertility parameters, including history of conceptions, will be performed 5 and 10 years after gonadotoxic therapies (long-term fertility). Additionally, the proportion of patients undergoing fertility-preserving procedures, their satisfaction with these procedures, and the amount of gametes and gonadal tissue and the children achieved by using the frozen material will be analyzed. Third, the data will be merged to create the internet-based data platform FertiTOX. The platform will be structured in accordance with the ICD (International Classification of Diseases) classification of cancer diseases and will be easily be accessible using a specific App. Several funding bodies have funded this study. Ten systematic reviews are in progress and the first one has been accepted for publication. All Swiss and many German and Austrian ethics committees have provided their approval for the prospective cohort study. The study registry has been set up, and a study website has been created. In total, 50 infertility centers have already been prepared for data collection, which started on December 1, 2023. The study can be expected to bridge the data gap regarding the gonadotoxicity of cancer therapies to better counsel patients about their infertility risk and their need to undergo fertility preservation procedures. Initial data are expected to be uploaded on the FertiTOX platform in 2026. ClinicalTrials.gov NCT05885048; https://clinicaltrials.gov/study/NCT05885048. DERR1-10.2196/51145.

Female cancer survivors: sexual function, psychological distress, and remaining fertility

PurposeImproved survivorship in cancer patients leads to new challenging issues including potential impairment of quality of life, sexual function, and fertility. The aim of this study was to assess sexual dysfunction (SD) and psychological distress in female cancer survivors who underwent fertility preservation in the past in comparison to reviewed healthy control data from other published studies. Additionally, our focus was on the difference in SD between women with current desire to get pregnant and already completed family planning.MethodsIn this prospective study, 53 female cancer survivors who underwent fertility preservation at time of cancer diagnosis between 2010 and 2020 were invited to a gynecological exam, laboratory assessment, and two questionnaires (Female Sexual Function Index (FSFI) and Hospital anxiety and depression scale (HADS)) in 2022. These scores were compared to results in the literature of healthy controls and depending on anti-Mullerian-hormone (AMH) levels, current desire to have a child, and age.ResultsAfter a mean follow-up time of 70 ± 50 months, SD was detected in 60.4% (n = 32) of the 53 included patients. Normal results regarding HADS-D/anxiety and HADS-D/depression were found in 88.7% and 94.3% of patients, respectively. At time of follow-up, 69.9% (n = 40) regained regular menstrual cycles, 52.6% (n = 20) < 40 years showed a diminished ovarian reserve with AMH levels < 1.1 ng/ml and 28.3% (n = 15) suffered from infertility.ConclusionFemale cancer survivors may be at risk for SD. Cancer patients should be informed about possible sexual dysfunction already at the start of cancer treatment and during follow-up. In addition, contraception needs to be addressed if regular cycles occur as more than two-thirds of the women regained regular menstrual cycles.

Decision regret, and other mental health outcomes, following fertility preservation in the transgender individual compared to the cisgender woman.

This study aimed to (1) determine differences in depression, anxiety, body image, quality-of-life (QOL), and decision regret scale (DRS) scores in transgender individuals undergoing fertility preservation (FP) compared to those who decline and (2) determine if DRS score following FP varies between transgender individuals and cisgender women. Sixteen transgender birth-assigned (BA) females and 13 BA males, undergoing FP consultation at an academic center between January 2016 and November 2019, were compared to each other and cisgender cohorts with pre-existing data: 201 women undergoing elective oocyte cryopreservation (EOC) between 2012 and 2016 and 44 women with cancer undergoing FP between 1993 and 2007. Outcomes included demographics; validated scales for depression, anxiety, body image, QOL (see below) in the trans cohort; DRS score in all three cohorts. Of 29 transgender individuals participating, 10 BA females (62%) and 12 BA males (92%) underwent FP. Beck Depression Inventory II, Hospital Anxiety and Depression Scale, Body Image Scale for Transsexuals, Satisfaction with Life Scale, Short Form Health Survey-36, and DRS scores were not significantly different between trans individuals who underwent FP and those who declined. On univariate modeling, regret was significantly lower in transpeople undergoing FP compared to those who did not (OR 0.118, p = 0.03). BA female and BA male transpatients undergoing FP reported DRS median scores 5 (mean 9) and 7.5 (mean 15), respectively, both were not significantly different from cisgender women (p = 0.97, p = 0.25) nor from each other (p = 0.43). Depression, anxiety, body image, and QOL, in a group of individuals presenting for FP consultation, appear similar between transpeople undergoing FP and not, while regret is significantly lower in those choosing FP. FP is an option for transgender individuals without significant differences in regret compared to cisgender women.

Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort

BackgroundFertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients.MethodsWe conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients.ResultsOut of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828–0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05).ConclusionWe have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.

Sexual and Reproductive Health Care after Gonadotoxic Treatment in Females at a Tertiary Pediatric Hospital

Study ObjectivesRecommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes. MethodsFollow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion. ResultsWe included 140 patients, with a mean time of 2.7 years from treatment completion. Eighty-six patients were 12 years old or older, of whom sexual activity was recorded in 59 (68.7%), and 12 of 31 (38.7%) sexually active patients underwent sexual function assessment. The 57 (66.3%) patients at high risk of premature ovarian insufficiency (POI) at diagnosis were more likely than minimal-risk counterparts (29, 33.7%) to have abnormal uterine bleeding (42.1% vs 17.2%, P = .03), to be diagnosed with POI (29.8% vs 0%, P = .01), and to have sexual activity recorded (77.2% vs 51.7%, P = .03). Of 17 patients with POI, 82.4% were on hormone replacement therapy, and 58.8% had undergone bone mineral density testing. ConclusionThis study adds to the limited literature regarding non-fertility-related SRH outcomes after gonadotoxic therapy and illustrates opportunities to improve adherence to the COG-LTFU guidelines. Increased attention to SRH guidelines may increase detection and treatment of SRH conditions, improving the health and quality of life of female cancer survivors.