Fertility and Pregnancy-Related Issues in Young BRCA Carriers With Breast Cancer.

Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 (BRCA1) or BReast CAncer 2 (BRCA2) genes. Preclinical and clinical studies showed a potential negative effect of germline BRCA1/2 (gBRCA1/2) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young gBRCA1/2 PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young gBRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment.

Current practices in oncofertility counseling: updated evidence on fertility preservation and post-treatment pregnancies in young women affected by early breast cancer.

INTRODUCTION: Anticancer treatments have significantly contributed to increasing cure rates of breast cancer in the last years; however, they can also lead to short- and long-term side effects, including gonadotoxicity, and compromised fertility in young women. Oncofertility is a crucial issue for young patients who have not yet completed their family planning at the time of cancer diagnosis. AREAS COVERED: This review aims to cover all the latest available evidence in the field of oncofertility, including the gonadotoxicity of currently adopted anticancer therapies in the curative breast cancer setting, the available strategies for fertility preservation and the feasibility of achieving a pregnancy following anticancer treatment completion. EXPERT OPINION: Over the past years, a significant progress has been made in oncofertility care for young women with breast cancer. In the context of the currently available evidence, every young woman with newly diagnosed breast cancer should receive a proper and complete oncofertility counseling before starting any anticancer treatment to increase her chances of future pregnancies.

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.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05885048; https://clinicaltrials.gov/study/NCT05885048. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51145.

High dose gonadotropin stimulation increases endometrial thickness but this gonadotropin induced thickening does not have an effect on implantation.

INTRODUCTION: Endometrial thickness <8 mm is related with lower pregnancy rates. This raises the question if endometrial thickness can be increased by gonadotropin stimulation to increase estradiol (E2) concentration and if such an artificial thickening of the endometrium has an effect on implantation. A model to address this question is the comparison of endometrial thickness and outcome parameters in conventional gonadotropin stimulated IVF (cIVF) compared to unstimulated natural cycle IVF (NC-IVF). MATERIAL AND METHODS: Retrospective study including 235 cIVF and 616 NC-IVF cycles without embryo selection and with fresh transfer on day 2 and 3 from 2015 to 2019. Endometrial and E2 measurements were included and analysed between day -4 and -2 (0 = day of aspiration). The effects of E2 on endometrial thickness, endometrial growth and the effect of endometrial thickness on implantation rates and live births were analysed. RESULTS: Endometrial thickness was found to be higher in cIVF compared to NC-IVF (p < 0.001). On day -2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ± 2.05 mm and 8.12 ± 1.66 mm, respectively. The increase in endometrial thickness slowed down with increasing E2 concentrations (time x estradiol concentration: -0.19, p = 0.010). Implantation rates were not significantly different in cIVF and NC-IVF cycles (clinical pregnancy rate: 19.1% vs. 15.4% p = 0.2; live birth rate: 12.8% vs. 11.7%, p = 0.8). CONCLUSIONS: Endometrial growth dynamic is different and endometrium is thicker in cIVF compared to NC-IVF. Pregnancy and live birth rates are not different. Gonadotropin induced thickening of the endometrium does not appear to improve implantation.