Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial.

Purpose: The POSITIVE trial showed that premenopausal women with breast cancer (BC) can safely pause adjuvant endocrine treatment (ET) to attempt conception. 74 % of patients conceived spontaneously or through assisted reproductive technology (ART); Investigating hormonal factors that predict fertility was a key secondary endpoint.

Methods: Hormonal factors were assessed in non-pregnant women at months 3, 6, and 12 after ET interruption.

Carboplatin and paclitaxel induced-gonadotoxicity on the ovarian reserve of young breast cancer patients with BRCA1 mutation.

Study Question: Are ovarian tissue fragments from patients with BReast CAncer gene 1 (BRCA1)-mutated breast cancer (BC) more sensitive to carboplatin and/or paclitaxel exposure compared to those from non-mutated patients with BC?

Summary Answer: Carboplatin and paclitaxel treatment showed similar gonadotoxicity, irrespective of the genetic background.

What Is Known Already: Studies have shown that mutations of BRCA1 gene negatively impact the ovarian reserve due to defects in DNA repair mechanisms. As a result, patients with BRCA germline mutations might be more vulnerable to chemotherapy-induced gonadotoxicity.

Breastfeeding after breast cancer in young BRCA carriers.

Background: We investigated safety of breastfeeding after breast cancer in patients carrying germline BRCA pathogenic or likely pathogenic variants.

Methods: This was an international, multicentre, hospital-based, retrospective cohort study including BRCA carriers diagnosed with stage I-III invasive breast cancer at age 40 years or younger between January 2000 and December 2020 (NCT03673306). Locoregional recurrences and/or contralateral breast cancers, disease-free survival (DFS) and overall survival (OS) were compared between patients who breastfed after delivery and those who did not.

Assisted reproductive technology in young BRCA carriers with a pregnancy after breast cancer: An international cohort study.

Introduction: Very limited data exist on assisted reproductive technology (ART) use in BRCA1/2 carriers conceiving after breast cancer. This study aimed to investigate the safety of ART to achieve a pregnancy after breast cancer in BRCA1/2 carriers.

Methods: This is an international, hospital-based, retrospective cohort study including BRCA1/2 carriers with a pregnancy after prior breast cancer diagnosis at ≤ 40 years of age between 2000 and 2020.

The Effects of Endometriosis on Oocyte and Embryo Quality.

Endometriosis is a complex and multifaceted gynecological disorder characterized by the abnormal growth and presence of endometrial-like tissue outside the confines of the uterine cavity. It can lead to a wide range of distressing symptoms, including chronic pelvic pain, heavy and/or irregular menstrual bleeding, and significant challenges with fertility. While the association between endometriosis and infertility is well recognized, the precise mechanisms through which the disease affects oocyte and embryo quality remain controversial.

Can we really protect the ovary from chemotherapy damage?

Future alternatives to current fertility preservation methods such as pharmacological strategies to prevent chemotherapy-induced ovarian damage in female cancer patients are of growing interest. Chemotherapeutic agents, especially alkylating agents, cause DNA damage and apoptosis in ovarian follicles, significantly reducing ovarian reserve. To mitigate this gonadotoxicity, various emerging strategies are being explored, including kinase inhibitors, PI3K/Akt/mTOR pathway inhibitors, antioxidants, miRNAs and GnRH agonists.

Effect of Surface Modification of Gold Nanoparticles Loaded with Small Nucleic Acid Sequences on Cytotoxicity and Uptake: A Comparative Study In Vitro.

Nanoparticle technology, particularly gold nanoparticles (AuNPs), is being developed for a wide range of applications, including as a delivery system of peptides or nucleic acids (NA). Their use in precision medicine requires detailed engineering of NP functionalization to optimize their function and minimize off-target toxicity. Two main routes can be found in the literature for the attachment of NA strands to AuNPs: covalent binding via a thiol group or passive adsorption onto a specially adapted coating previously applied to the metallic core.

Perinatal outcomes of pregnancies following autologous cryopreserved ovarian tissue transplantation: a systematic review with pooled analysis.

Objective: This study aimed to synthesize the existing evidence on perinatal outcomes after autologous cryopreserved ovarian tissue transplantation, concurrently identifying key factors influencing these outcomes.

Data Sources: A comprehensive search was performed on MEDLINE, Embase, and Cochrane Library databases to identify relevant studies on the effect of autologous cryopreserved ovarian tissue transplantation on perinatal outcomes from inception to October 22, 2023. Where there was missing information, the authors were contacted for updated data.

The Role of microRNA in Spermatogenesis: Is There a Place for Fertility Preservation Innovation?

Oncological treatments have dramatically improved over the last decade, and as a result, survival rates for cancer patients have also improved. Quality of life, including concerns about fertility, has become a major focus for both oncologists and patients. While oncologic treatments are often highly effective at suppressing neoplastic growth, they are frequently associated with severe gonadotoxicity, leading to infertility.

BRCA Mutations and Fertility Preservation.

Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in () genes are responsible for the majority of cases of hereditary breast and ovarian cancer. and act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination.

A Journey to Reach the Ovary Using Next-Generation Technologies.

Although effective in terms of the chances of future live birth, the current methods for fertility preservation, such as oocyte, embryo, or ovarian tissue cryopreservation, cannot be offered to all cancer patients in all clinical contexts. Expanding options for fertility preservation is crucial to addressing the need to encompass all situations. One emerging strategy is pharmacoprotection, a non-invasive approach that has the potential to fill existing gaps in fertility preservation.

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition.

The combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy is the standard treatment for patients with HR+/HER2- advanced breast cancer. Recently, this combination has also entered the early setting as an adjuvant treatment in patients with HR+/HER2- disease at a high risk of disease recurrence following (neo)adjuvant chemotherapy. Despite their current use in clinical practice, limited data on the potential gonadotoxicity of CDK4/6 inhibitors are available.

Regulation of follicular activation signaling pathways by in vitro inhibition of YAP/TAZ activity in mouse ovaries.

The Hippo pathway plays a crucial role in the regulation of follicular activation, which constitutes the first step of the folliculogenesis process. Disruption of this pathway occurs in several non-physiological contexts, after fragmentation for ovarian tissue cryopreservation procedures or chemotherapy exposure, leading to massive follicular growth and depletion. This study aimed to investigate the effect of controlling the Hippo pathway using verteporfin (VERT) during in vitro ovarian culture and to evaluate its potential preventive effects on chemotherapy-induced follicle activation using a mouse model.

Impact of Breast Cancer and Germline BRCA Pathogenic Variants on Fertility Preservation in Young Women.

Background: Several studies have suggested that breast cancer (BC) and germline BRCA pathogenic variants (gBRCA PVs) could have a deleterious impact on ovarian reserve. Nevertheless, data are limited and mixed. Our objective was to evaluate the performance of fertility preservation (FP) in terms of the number of collected mature oocytes after ovarian stimulation (OS) in young women carrying a gBRCA PV, associated or not with BC.

Gene Expression Analyses in Human Follicles.

The ovary is a heterogeneous organ composed of different cell types. To study the molecular mechanisms occurring during folliculogenesis, the localization of proteins and gene expression can be performed on fixed tissue. However, to properly assess gene expression levels in a human follicle, this complex and delicate structure must be isolated.

Impact of first chemotherapy exposure on follicle activation and survival in human cryopreserved ovarian tissue.

Study Question: Does chemotherapy exposure prior to ovarian tissue cryopreservation (OTC) impact the signaling pathways governing follicle activation and survival for prepubertal and postpubertal patients?

Summary Answer: Chemotherapy exposure prior OTC increases follicle apoptosis rates but not follicular activation, although the PI3K/AKT/mTOR and Hippo signaling pathways were modified in the cortex.

What Is Known Already: OTC is currently the only available fertility preservation procedure for children and for patients who have already started their treatment. While previous studies have not observed harmful impacts of first chemotherapy exposure on OTC outcomes, the consequences of treatment on follicle activation and survival need to be further investigated.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity.

Patients And Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy).

Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study.

Introduction: Fertility preservation (FP) is recommended in young breast cancer (BC) patients before (neo)adjuvant treatment. Letrozole-associated controlled ovarian hyperstimulation (LetCOH) is used worldwide to collect mature oocytes for FP, but its efficacy and safety compared to conventional protocols (cCOH) are still debated.

Aims: To compare efficacy and safety of FP procedure using LetCOH or cCOH in BC patients in terms of oocyte maturation rate and disease-free survival rates after at least two years of follow-up.

Let-7a mimic transfection reduces chemotherapy-induced damage in a mouse ovarian transplantation model.

Pharmacological approaches offer a non-invasive and promising option for fertility preservation in young female cancer patients undergoing gonadotoxic therapy. The GnRH-agonists are the only clinically available drugs in this indication, but their use and mechanisms of protection are still controversial. Recently, we have investigated new targeted drugs based on microRNA (miRNA) replacement therapy, and have identified the let-7a miRNA as candidate for fertility preservation strategies.