Cancer Patients Of Reproductive Age Research Articles

The effect of antitumor therapy on the reproductive system, the possibility of preserving female fertility

The influence of malignant neoplasms and their treatment methods on the reproductive function of women is one of the significant problems of oncogynecology. The mechanisms of ovarian follicle loss caused by chemotherapy have their own characteristics depending on the characteristics of the cytotoxic agent and act differently on different populations of ovarian cells. The toxic effect on fertility of the main groups of antitumor drugs is considered. Reproductive dysfunction has negative consequences for a woman’s physical and mental health. The use of methods that reduce the effect of cytotoxic agents on the ovary helps to prevent premature ovarian insufficiency, leading to infertility. The article discusses modern methods of fertility preservation using assisted reproductive technologies. All cancer patients of reproductive age should receive full oncofertility counseling as early as possible, during the treatment planning process, regardless of the type and stage of the disease.

Abstract 2233: Limited adherence to clinical practice guidelines on fertility preservation for patients with early-onset cancer

Abstract Background: ASCO Clinical Practice Guidelines on fertility preservation (FP) recommend that healthcare providers discuss the possibility of infertility—including FP options—for cancer patients of reproductive-age as early as possible before treatment initiation. However, the evaluation of patient perceptions on provider adherence to these FP guidelines is largely undetermined. We sought to assess patient-reported provider adherence to FP guidelines for adults ages 18 to 49 years when diagnosed with a first primary cancer (early-onset). Patients and Methods: The Reproductive Health After Cancer Diagnosis and Treatment (REACT) Study is a patient-partnered study in cooperation with 23 community partners and patient advocates. Adults with a first primary early-onset cancer were recruited over an 8-week period (October to December 2021). Patient-reported provider adherence to FP guidelines, reproductive health history, sociodemographic, cancer and cancer impact questions were prospectively collected via patient questionnaire using a secure, web-based application. To examine the association of provider non-adherence with patient-level factors, logistic regression models were fitted to estimate odds ratios (OR) and 95% CI. Results: Among 647 patients diagnosed with early-onset cancer between 2006 and 2021 (mean [SD] age, 36.8 [7.8] years), a total of 376 (58.1%) reported that a healthcare professional involved in their cancer care did not discuss FP options before starting cancer treatment. Patients with thyroid, lung, ovarian and colorectal cancers reported the highest rates of provider non-adherence to FP guidelines (all ≥63% non-adherence). Females with cervical (OR 2.87, 95% CI: 1.11-7.41), colorectal (OR 2.05, 95% CI: 1.15-3.68), lung (OR 15.79, 95% CI:5.66-44.1) and ovarian (OR 10.90, 95% CI: 3.19-37.3) cancers, Hodgkin (OR 4.00, 95% CI: 1.15-13.98) and non-Hodgkin lymphoma (OR 4.65, 95% CI: 1.11-19.47) were more likely to report provider non-adherence to FP guidelines compared to breast cancer patients in models adjusted for diagnosis age and year, self-reported race/ethnicity, marital status and insurance coverage at cancer diagnosis. Similar patterns were observed for male patients with early-onset colorectal and lung cancers compared with testicular cancer patients. No overall or sex-specific associations were observed between patient-reported provider non-adherence and race/ethnicity, insurance coverage or diagnosis year. Conclusions: Nearly six of every 10 early-onset cancer patients reported that a healthcare professional involved in their cancer care did not discuss FP options prior to cancer treatment. The development of tailored, effective strategies for implementation of clinical practice guidelines on FP and delivery of concordant reproductive healthcare to a growing population of reproductive-age individuals with cancer is needed. Citation Format: Samantha R. Keller, Mark A. Lewis, Allison Rosen, Hyo K. Park, Rebecca Babyak, Jill Feldmann, Fei Ye, Rajiv Agarwal, Kristen K. Ciombor, Timothy M. Geiger, Cathy Eng, Michelle K. Roach, Digna R. Velez Edwards, Michele L. Cote, Richard Viskochil, Andreana N. Holowatyj. Limited adherence to clinical practice guidelines on fertility preservation for patients with early-onset cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2233.

#389 : Fertility Preservation During Chemotherapy Treatment by NAD+ Repletion in Mice

Background and Aims: Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to prevent chemotherapy induced infertility are urgently needed. Here we investigate whether pharmacological elevation of nicotinamide adenine dinucleotide (NAD+) ameliorates chemotherapy induced female infertility in mice. Method: 8-week-old C57BL6 female mice were treated +/- chemotherapy (doxorubicin, Dox; 10 mg/kg) and +/- nicotinamide mononucleotide (NMN; 200 mg/kg i.p. once and 2 g/L in drinking water on-going), an orally bioavailable metabolic precursor to NAD+. Effects on fertility were measured by impact on ovarian reserve and folliculogenesis, ovulation rates and breeding performance. Effects on the ovarian NAD+ metabolome were assessed by mass spectrometry. A potential adverse effect of NMN on the efficiency of chemotherapy was assessed using a xenograft model of mammary cancer. Results: NMN treatment did not prevent a decline in the ovarian reserve caused by chemotherapy but did maintain the health of the remaining primordial follicle and total follicle populations, leading to a restoration in oocyte yield in chemo-treated mice (Dox vs Dox+NMN; P<0.007), culminating in an increase in pups born/mating in chemo+NMN treated mice (P<0.05). Chemo caused ovarian NMN, NADP+ and NADPH depletion, and NADPH was restored by NMN, which likely contributes to Dox detoxification. Importantly, treatment of the breast cancer mouse model with NMN reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Conclusion: Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function and fertility in cancer patients, with potential benefits in cancer therapy.

Mediation Effects of Coping Styles on Fear of Progression and Reproductive Concerns in Breast Cancer Patients of Reproductive Age

PurposeThis study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients. MethodsA cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns after Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns. ResultsReproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r=.52, p<.01). At the same time, confrontation was significantly negatively correlated with both FOP (r=−.28, p<.01) and reproductive concerns (r=−.39, p<.01). Avoidance was positively correlated to both FOP (r=.25, p<.01) and reproductive concerns (r=.34, p<.01). The impact of fear of progression on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect. ConclusionThe FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' fear of progression, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns.

Differences in oncofertility beliefs, knowledge, and practice between medical oncologists and advanced practice providers: Identifying quality improvement targets.

e18747 Background: Despite the deleterious effects of systemic cancer treatment on fertility, many young adult cancer patients do not receive fertility preservation. Historically, oncofertility was discussed by the medical oncologist (MO), but an increasing advanced practice provider (APP) oncology workforce provides opportunities for quality improvement (QI) in oncofertility care. To identify levers for QI interventions, we explored how fertility beliefs, knowledge, and practice of MOs differ from APPs. Methods: MOs and APPs working in inpatient, outpatient, academic and community clinical settings were identified from providers at The Jonsson Comprehensive Cancer Center (JCCC). Participants completed an online survey prior to a fertility preservation seminar. Survey questions queried beliefs about fertility preservation, knowledge about guideline recommendations, and individual fertility practices in the 3 months prior to survey completion. Responses were collected anonymously through a HIPAA-compliant web platform. Pearson chi-squared and two-sample T tests were used for statistical comparisons between MOs and APPs using STATA v15.1. This study received exempt status from the University of California Los Angeles (UCLA) Institutional Review Board. Results: 32 (52.5%) APPs and 29 (47.5%) MOs completed the survey. APPs were younger than MOs (28% vs. 14% were 30-39 years, p = 0.072) and more frequently female (91% vs. 38%, p &lt; 0.001). Practice specialties varied equally between both groups and they had similar distribution of post-training oncology experience. Participants saw an average of 6.0 (APP) and 5.7 (MO) new cancer patients of reproductive age per month. While APPs and MOs reported concern about the effects of cancer treatment on fertility, APPs were more likely to agree with the statement “Offering fertility preservation to patients before cancer therapy compromises their oncological treatment” than MOs (44% vs. 31%, p = 0.047). APPs reported less familiarity with fertility preservation guidelines (scale 0-10, mean 4.3 vs. 5.8, p = 0.013) and MOs were more comfortable discussing specific fertility preservation techniques. There were no significant differences in referral practices. In the 3 months prior to survey, MOs reported having fertility discussions more frequently than APPs (52% vs 28%, p = 0.047) and more regularly had discussions before treatment initiation (97% vs. 78%, p = 0.033). Conclusions: Improving oncofertility care for young cancer patients is an important quality metric. This exploratory study demonstrated significant differences in beliefs, knowledge, and practice between MOs and APPs regarding fertility preservation for cancer patients. These results will shape our future QI initiatives, which will target system, practice, and education with a specific focus on non-MO providers.

Fertility Preservation Knowledge, Attitudes, and Self-Reported Behaviors of Resident Physicians.

Purpose: Fertility preservation (FP) and family building are important considerations for quality survivorship for young cancer patients. Resident physicians across all specialties encounter reproductive-aged cancer patients. The purpose of this study was to assess resident physicians' attitudes and awareness about FP with the goal to identify specific educational gaps to direct future training. Methods: The Institutional Review Board (IRB)-approved anonymous online survey was sent to resident physicians across specialties at three separate academic-affiliated campuses in one state. The survey consisted of three sections: awareness about FP options and knowledge about referral placement, attitudes and comfort levels discussing FP, and practices regarding FP. Data were collected in Qualtrics and analyzed by resident specialty, age, level of training, and gender. Statistical analyses were conducted with Prism. Results: Obstetrics and gynecology residents and fellows were significantly more aware of FP options in cancer patients than their counterparts in other specialties. Postgraduate year (PGY 3) residents and beyond were more aware of at least one male and one female FP option compared with PGY 1 and 2 residents. Of importance, we found that the majority of resident physicians are aware of FP options and the referral process, but they are uncomfortable discussing these techniques with their patients. Conclusion: To provide better education for patients, focus should be on outpatient educational activities for both the health care provider and the patient to facilitate conversation about FP.

Abstract P5-07-02: Embryo utilization in young breast cancer patients who have undergone egg harvesting for fertility preservation

Abstract INTRODUCTION: Much progress has been made related to fertility preservation in women diagnosed with breast cancer. This includes heightened awareness of impaired fertility due to breast cancer treatment, increased referrals to fertility specialists and development of safe and expeditious means of egg harvesting. Nevertheless, there has been limited investigation of the ultimate issue in fertility preservation, namely the frequency with which women who have undergone egg harvesting actually pursue childbearing. We have retrospectively reviewed a single institution’s experience with egg and embryo utilization among patients who expressly desired childbearing and underwent egg harvesting after a diagnosis of breast cancer. These issues have also been analyzed relative to race and insurance coverage. METHODS: In an IRB approved study, breast cancer patients treated in our institution between 2010 and 2020 were identified and their post-diagnosis fertility and childbearing history was reviewed. Inclusion criteria were age at presentation ≤ 45 years and diagnosis of either invasive breast cancer or ductal carcinoma in situ. Race (self-reported on clinic intake form) and insurance coverage data were analyzed. In cases of incomplete medical record data, we interviewed patients by telephone. RESULTS: 316 breast cancer patients of reproductive age were identified (average age at diagnosis = 39 years, range: 23 - 45). Of these, 168 patients (53%) were offered fertility referral and 118 (38%) saw a fertility specialist. 91 patients (29%) pursued egg harvesting followed by cryopreservation of eggs in 49 cases and embryos in 41 with 1 case unknown. Over an average of 5 years of follow-up (range: 2 - 12 years), 28 women (31% of those who pursued egg harvesting) utilized the egg or embryo to pursue childbearing. 17 underwent embryo transfer to themselves and 11 used surrogate carriers. To date, this has resulted in 20 childbirths from 24 pregnancies. Four pregnancies are currently ongoing and 1 woman is awaiting embryo transfer. Four patients who had undergone egg harvesting conceived without fertility intervention. Of the 55 Medicaid patients of reproductive age diagnosed with breast cancer, only 8 (15%) met with a fertility specialist, 4 harvested eggs, and none pursued childbearing. HMO/PPO insured patients were significantly more likely than Medicaid patients to pursue egg harvesting and embryo utilization (X2 = 7.320, df = 2, p = 0.026). Of 260 HMO/PPO insured patients, 110 (42%) met with a fertility expert, 87 harvested eggs and 28 pursued embryo transfer. Due to the small sample size of patients who utilized embryos in each racial subgroup, analysis did not yield statistically significant differences across groups (p=0.067). Nevertheless, apparent racial disparities exist. Our data reveal that 5 of 17 (29%) Asian patients and 22 of 62 (36%) White patients utilized embryos as opposed to Black patients (1/4 or 25%), Hispanic patients (0/4 or 0%) and those who identified their race as “other” (1/4 or 25%). CONCLUSIONS: These data demonstrate a low overall rate of cryopreserved egg and embryo utilization among women treated for breast cancer whose earlier pursuit of egg harvesting was evidence of a desire for childbearing. Furthermore, racial and insurance data demonstrate disparities in the pursuit of fertility treatment and utilization of preserved eggs and embryos. Further research will utilize interviews to analyze individual women’s decision-making process relevant to such issues as hormone therapy utilization, concerns about breast cancer recurrence, progression of disease and restraints imposed by relationship status and finances. Given the disparity findings reported here, finances will likely emerge as a significant barrier to childbearing in future qualitative research. Citation Format: Christina Weltz, Daniella Nevid, Alison Pruzan, Elisa Port, Ronald Couri. Embryo utilization in young breast cancer patients who have undergone egg harvesting for fertility preservation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-02.

Perspectives and Knowledge about Fertility Preservation Strategies among Female Cancer Patients in Turkey.

To evaluate the knowledge level and perspectives of female cancer patients regarding fertility preservation techniques before gonadotoxic treatment. Material and Methods. This was a prospective observational survey-based study conducted between 2016 and 2020 in Izmir Economy University Medical Park Hospital. A total of 150 female cancer patients aged 18-42 years were included. The participants completed a 17-item questionnaire, developed by the research team to evaluate their knowledge and perspectives on fertility preservation techniques. The mean age of the patients was 39.5 ± 4.9 years. Only 64.7% of the patients were referred to fertility counseling by a gynecologist, while 72.6% of the patients knew of the risk of infertility after cancer treatment. There was a significant correlation between the health status and cancer stage of the patient (p=0.003). The estimated future chance of becoming pregnant spontaneously or through fertility preservation techniques was significantly higher in patients with a higher education level (p=0.041 or 0.008, respectively). Satisfaction with the counseling process was reported as high or low by 66.7% or 20% of the patients, respectively. The rate of referral of reproductive-age cancer patients to fertility preservation counseling is still not satisfactory. Education level was the only variable significantly associated with a motivation to become pregnant after cancer treatment, either spontaneously or through fertility preservation techniques.

Outcomes of Fertility Preservation for Female Cancer Patients in a Single Tertiary Center.

To report our experience of fertility preservation (FP) in female cancer patients. We retrospectively analyzed the medical records of female who underwent elective oocyte or embryo cryopreservation before cancer treatment between January 2015 and December 2020 at Asan Medical Center. We analyzed the type of cancer, the rate of reuse of cryopreserved oocytes or embryos, and fertility outcomes such as the resumption of menstruation or pregnancy. A total of 174 patients underwent 182 oocyte retrieval cycles after controlled ovarian stimulation for oocyte or embryo cryopreservation. The median age of patients was 33.0 (range 19-46) years, and the patients were most unmarried female (65.52%). The majority of patients were diagnosed with breast cancer (78.16%), and the remaining were diagnosed with gastrointestinal (6.33%) and hematologic malignancies (5.75%). The maturation rate of oocyte cryopreservation was 83.33%, and the fertilization rate of embryo cryopreservation was 72.07%. Of the 57 patients currently not undergoing cancer treatment, 34 resumed menstruating and 19 (33.33%, 19/57) returned to attempt a pregnancy. Among them, five patients succeeded in natural pregnancy. Eleven patients received frozen-thawed embryo transfer, and four patients succeeded in becoming pregnant (36.36%, 4/11). Only 6.3% of patients returned to use their gametes, and 93.7% of gametes are still in storage. FP in cancer patients should be considered before cancer treatment. Through continuous research on oncofertility, it is necessary to consider how to increase the return rate and provide appropriate information to cancer patients of reproductive age.

Muscle mass loss in breast cancer patients of reproductive age (≤ 45years) undergoing neoadjuvant chemotherapy.

Loss of muscle mass is associated with negative clinical outcome in breast cancer (BC) patients. Therefore, the aim of the study is to evaluate if there is pectoralis muscle area (PMA) depletion, reflecting loss of muscle mass, in breast cancer patients of reproductive age (≤ 45years) undergoing neoadjuvant chemotherapy (NAC) and to correlate PMA with clinical and histopathological data. This monocentric study, approved by our institutional review board, enrolled a total of 52 consecutive patients (mean age 37 ± 4.96years) with histologically proven primary breast cancer between January 2019 and September 2021, treated with NAC and in whom tumor response and PMA were assessed with breast MRI. Two radiologists calculated PMA before and after NAC independently and blindly on axial 3D FLASH pre-contrast T1-weighted images. Wilcoxon-Mann-Whitney U test compared median values and percentage changes of pectoralis muscle area at the beginning and at the end of NAC (158 ± 25.5days). Multivariate regression analysis on ΔPMA (difference between PMA pre-NAC and PMA post-NAC) was done according to clinical and histopathological data. Inter-reader and intra-reader agreement was estimated with K statistics. Pre-NAC PMA mean value was larger than post-NAC PMA mean value (9.6 ± 2.6cm2 vs. 8.7 ± 2.2cm2, p < 0.001, delta value 1.41). According to the RECIST criteria, no significant differences between complete and partial response were found. Multivariate regression analysis did not show any significant relationships between ΔPMA and age, time between MRI examinations, estrogen and progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 expression, lymph node involvement, RECIST criteria, histological type, and different regimes of NAC. Inter-reader (k = 0.74) and intra-reader agreement (0.67 and 0.73) in PMA assessment was good. PMA variation in BC young patients, directly estimated on breast MRI, could be a potential tool to monitor body composition during NAC with potential implications in improving outcome.

Oncofertility care and influencing factors among cancer patients of reproductive age from Saudi Arabia.

More cancer survivors and a greater burden of long-term side effects have resulted from rising cancer incidence, improved treatment modalities, and younger age at cancer diagnosis. Treatment- related Infertility (TRI) is a well-known sequelae. This study looked at current oncofertility support and fertility preservation (FP) in men and women of reproductive age with cancer in Saudi Arabia, where there is little knowledge on the subject. A cross-sectional study included oncology patients of reproductive age from an academic hospital was conducted. Patients' characteristics, cancer type, treatment modalities and assessment of oncofertility support data were collected and examined to assess oncofertility support and potentially influencing factors. Our study included 135 patients (39.3% males and 60.7% females). Although 66.7% believed they were fertile at the time of diagnosis, and more than half planned to have children in the future, Unfortunately, only 37.8% have received fertility counseling, and only 17% have seen a fertility specialist. In male patients, the most common FP method was sperm cryopreservation (6.7%), while the majority of both genders (87.4%) did not use any FP method. Two-thirds of the patients are knowledgeable about TRI and FP methods. About half of the female patients (57.3%) were advised about the possibility of post-treatment amenorrhea while only 8.1% of the whole cohort received psychological support. Despite patients' satisfactory knowledge of TRI and FP, oncologists infrequently referred their patients to a specialized fertility service. More than half of our patients expressed a desire to have children in the future, but this desire was impeded by limited oncofertility care and FP procedures. Several factors influenced the knowledge of TRI, fertility counseling and FP. It is critical to incorporate oncofertility into management planning as it has a significant impact on patients' quality of life.

IDENTIFYING PREDICTIVE FACTORS FOR FERTILITY OUTCOMES AMONG FEMALES WITH OVARIAN NEOPLASMS

Ovarian cancer is the 6th most common cancer among females and the most fatal gynecologic cancer. The American Society of Clinical Oncology recognizes fertility preservation as a key survivorship issue and fertility preservation counseling is recommended for females of reproductive age prior to surgical or gonadotoxic chemotherapeutic treatment. Currently, there is little known regarding fertility preservation treatment (FPT) and fertility sparing surgery (FSS) among ovarian cancer patients of reproductive age.

Is letrozole during ovarian stimulation useful in breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist trigger?

BackgroundIn absence of contraindication, breast cancer patients of reproductive age can undergo fertility preservation with controlled ovarian stimulation for oocyte/embryo cryopreservation before the administration of potentially gonadotoxic treatments. High hormonal levels induced by ovarian stimulation might have an adverse impact on hormone-positive breast cancer. Whether letrozole supplementation during ovarian stimulation (COSTLES) reduces serum progesterone levels after GnRHa trigger remains unknown. We aimed to determine whether COSTLES might be useful for breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist (GnRHa)trigger.MethodsAll women who underwent COS with GnRH antagonist protocol with GnRHa trigger were included. Serum progesterone level measured 12 h after GnRHa trigger was compared between patients undergoing COS with letrozole supplementation (COSTLES group) and patients undergoing COS without letrozole (Control group) for fertility preservation purposes.ResultsA total of 246 patients were included, of which 84 patients (34.1%) in the COSTLES group and 162 patients (65.6%) in the Control group. All patients in the COSTLES group were BC patients (n = 84, 100%), while the Control group included 77 BC patients (47.5%). Patients in the two groups were comparable. The mean number of oocytes recovered and vitrified at metaphase 2 stage did not significantly differ between the two groups. Serum progesterone levels on the day after GnRHa trigger were significantly lower in the COSTLES group (8.6 ± 0.7 vs. 10.5 ± 0.5 ng/mL, respectively, p < 0.03), as well as serum E2 levels (650.3 ± 57.7 vs. 2451.4.0 ± 144.0 pg/mL, respectively, p < 0.01). However, the GnRHa-induced LH surge was significantly higher in in the COSTLES group (71.9 ± 4.6 vs. 51.2 ± 2.6 UI/L, respectively, p < 0.01).ConclusionsOur results show that COSTLES for fertility preservation in breast cancer patients using GnRHa trigger reduces serum progesterone levels compared to ovarian stimulation without letrozole. These findings encourage the use of COSTLES in this context to decrease the potential deleterious effect of elevated hormonal levels on hormone-positive breast cancer.

Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study.

Introduction. Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility. Although both national and international guidelines value reproductive counseling as an essential aspect of the diagnostic-therapeutic pathway, part and parcel of the informed consent process, it is not included within the protocols adopted by the operating units for the care and management of neoplastic diseases. Objective. This study aimed to evaluate the activity of the Breast Unit of the Policlinico Umberto I Hospital, Rome, Italy, and the degree of compliance with guidelines. By knowing the strengths and weaknesses of such approaches, the standards of care offered to breast cancer patients can be improved. Materials and methods. A retrospective study based on a review of medical records was conducted between 2014 and 2021. Patients under 40 years of age diagnosed with non-metastatic malignancies were included who received chemotherapy treatment, namely neoadjuvant, adjuvant or adjuvant hormone therapy. Results. The data were extracted from the medical records of 51 patients who met the inclusion criteria, 41% of whom received reproductive counseling, and of these, 43% decided to undertake a path of fertility preservation. Factors such as the absence of children and young age reportedly favored both the interest in counseling proposals by the medical staff and the decision to undertake a path of fertility preservation. Conclusions. The study shows that there has been growing interest in the topic of oncofertility, especially in light of law 219/2017. Therefore, since 2018, multiple proposals for reproductive counseling have been set forth, but there was not an equally growing demand for fertility preservation practices, which can be explained by the invasive nature of such practices, the patients’ concern about their own state of health, and poor or inadequate information. Such impediments highlight the importance of standardized counseling and the need for a multidisciplinary medical team to support the patient in the decision-making process. The study also revealed a drop in the number of patients receiving counseling due to the COVID-19 pandemic, contrary to the positive trend that was recorded prior to the pandemic.

Decision Making Process on Fertility Preservation in Female Breast Cancer Patients of Reproductive Age

Decision Making Process on Fertility Preservation in Female Breast Cancer Patients of Reproductive Age

A Review of Oncologist’s Knowledge and Awareness Regarding Fertility Preservation

The recent quantum leaps in various management modalities in oncology have led to unanticipated survival rates. This has constituted a plea for amelioration in the quality of life of cancer patients of reproductive age, at the core of which is Fertility Preservation (FP).

P–416 Radiotherapy inflicts long-term damage upon the uterus, causing uterine artery endothelial dysfunction and pregnancy loss in mice

Abstract Study question Does the uterus sustain direct and long-term damage following radiotherapy, independent of ovarian damage? Summary answer Radiotherapy causes direct and long-term uterine damage. Ovariectomised and hormonally supplemented mice experience uterine artery endothelial dysfunction and pregnancy loss following transfer of healthy blastocysts. What is known already The detrimental off-target impacts of cancer therapies on the ovary are well established, with some fertility preservation techniques available to ensure patients maintain their fertility following gonadotoxic treatment. Low doses of radiotherapy kill the majority of primordial follicle oocytes in the ovary, reducing the ovarian reserve and fertile lifespan. Patients who have received radiotherapy experience higher rates of pregnancy complications including preterm birth, low birth weight, and stillbirth. However, no studies have investigated if radiation inflicts direct, fertility compromising damage to the uterus. Study design, size, duration Adolescent female mice were untreated or exposed to whole body y-irradiation (7Gy), then ovariectomised. Immediate damage was assessed up to 24 hours post-irradiation (n = 4/group). Four weeks following treatment, mice were hormone primed to induce endometrial receptivity (n = 7/group), artificial decidualisation (n = 7–8/group), or receive embryo transfers from healthy, unexposed donor mice to assess embryo implantation (n = 11–13/group), and mid-gestation development (n = 8–10/group). Participants/materials, setting, methods Four week old C57BL6/CBA (F1) female mice were used for this study. Immunofluorescence and in situ hybridisation were utilised to localise markers of immediate DNA damage and cell death following irradiation, and markers of receptivity in hormone primed uteri. Measurements of uterine artery blood flow were recorded using Doppler ultrasonography, and indices of pulsatility and resistance calculated. Uterine artery wire myography was performed to assess competency of endothelial and smooth muscle compartments following irradiation. Main results and the role of chance Within 24 hours of irradiation, DNA damage (yH2AX) and apoptosis (Puma/TUNEL) were elevated in uteri, compared to control. Irradiated mice that received embryo transfers from untreated donors had similar numbers of implantation sites 3-days post-transfer versus controls, however uteri were pale and atrophic suggesting impaired vascularisation. By 10-days post-transfer, implantation sites in irradiated mice were resorbing (p &amp;lt; 0.001), although uterine artery Doppler ultrasound measurements demonstrated no change in pulsatility or resistance indices. When the brain was shielded from irradiation to protect the hypothalamic-pituitary-gonadal axis, resorption still occurred (p &amp;lt; 0.001), suggesting direct uterine damage is the likely cause of pregnancy loss. To investigate uterine damage in the absence of an embryo, endometrial receptivity was induced artificially. Uteri from irradiated animals were lighter compared to control (p &amp;lt; 0.05), however localisation of receptivity markers (E-cadherin, Mucin1, Ki67) was normal. When decidualisation was artificially induced irradiated uteri were also lighter (p &amp;lt; 0.01) indicating impaired decidualisation and reduced capacity to adapt to pregnancy. Wire myography performed on uterine arteries demonstrated endothelial dysfunction in irradiated mice (p &amp;lt; 0.0001). Limitations, reasons for caution Here, only a single age and dose of radiotherapy exposure are modelled. Patients of all ages can receive many doses of radiotherapy in combination with various chemotherapies. Our highly manipulable model enables any treatment variation to be modelled and the effect on the uterus and pregnancy examined. Wider implications of the findings: Reproductive aged cancer patients need to be appropriately counselled regarding the risks to their long-term fertility following treatment. Until now, potential permanent impacts to the uterus following cancer treatment have not been considered. It is clear radiotherapy can impose long-term damage to the uterus and influence pregnancy success and fertility. Trial registration number NA

Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40years or younger.

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

Navigating the Challenges of Fertility and Reproductive Planning for Terminal Cancer Patients

Among the many disruptive effects of a terminal cancer diagnosis in young people is its ability to affect reproductive planning and the opportunity for parenthood. While many reproductive-aged cancer patients receive fertility counseling at diagnosis, ongoing guidance often does not occur during the illness course and associated distress may go unrecognized. Using a case-based framework, this palliative care rounds explores the existential, spiritual, ethical, and logistical challenges that complicate reproductive planning for patients and families as they face a terminal cancer diagnosis. We advocate that palliative care providers should seize currently underrecognized opportunities to screen for distress associated with fertility and reproduction at end of life and utilize an interdisciplinary team approach to provide appropriate support and counseling throughout the illness and bereavement experience.

Use of fertility preservation services in male reproductive-aged cancer patients

While fertility preservation is a major concern among reproductive age cancer patients, little is known about access and use of fertility preserving services. We examined use of fertility preserving services among men with common solid tumors.A total of 3648 men age 18–40 including 2610 (71.6%) with testicular cancer, 939 (25.7%) with colorectal and 99 (2.7%) with prostate cancer were identified. Fertility preservation services were utilized in 9.3% of men overall including 4.1% who underwent fertility evaluation only and 7.8% who had a fertility preservation procedure. The rate of fertility preservation services rose from 6.6% (95%CI, 3.2–10.0) in 2008 to 12.4% (95%CI, 7.3–17.5) in 2017 (P = 0.04).Use of fertility preservation service was more common in patients with testicular (11.6%, aRR = 3.31; 95% CI 2.22–4.92) and prostate cancer (6.1%, aRR = 3.14; 95% CI 1.28–7.70) compared to those with colon cancer (3.4%). Younger men were more likely to utilize fertility preservation services. 11.5% of men age ≤ 35 years vs. 5.2% of men 36–40 used these services (P < 0.0001). Fertility preservation services were used in 10.8% of those who received chemotherapy (aRR = 1.81; 95% CI, 1.45–2.27) and in 8.1% of those who received radiation (aRR = 1.30 95% CI, 0.98–1.73). Medicaid patients were less likely to receive fertility preservation services than those with commercial insurance (0.7% vs. 10.1%; aRR = 11.58, 95%CI 2.10–63.69). These data indicate that while use of fertility preserving services is increasing, overall use of services is low among reproductive age males with cancer.