Another step towards improving oncofertility counselling of young women with Hodgkin's lymphoma

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Oncofertility counselling in premenopausal women with HER2-positive breast cancer

A complete oncofertility counselling should be offered to all premenopausal patients before the administration of anticancer treatments. This important discussion is a crucial step for allowing them to take fully informed decisions about the proposed therapy and its potential long-term consequences as well as on their need and interest of accessing the available strategies for ovarian function and/or fertility preservation. In premenopausal women with HER2-positive early breast cancer, limited evidence exists to counsel them about the potential added gonadotoxicity of targeted agents beyond the damage already caused by chemotherapy. In addition, the prognostic role of treatment-induced amenorrhea in this setting was unknown. In our exploratory analysis within the ALTTO (BIG 2-06) trial, we have recently described the rates of treatment-induced amenorrhea after chemotherapy plus trastuzumab and/or lapatinib and the prognostic value of developing this side effect according to the hormone receptor status of their tumours. We observed similar rates of treatment-induced amenorrhea in the four anti-HER2 treatment arms. The lack of an increased rate of treatment-induced amenorrhea in the dual anti-HER2 blockade arm suggests the possible gonadal safety of these agents. In addition, women with HER2-positive/hormone receptor-positive tumours showed significantly better survival outcomes if they developed treatment-induced amenorrhea, while no difference was observed for those with HER2-positive/hormone receptor-negative disease. Future research efforts are needed to address the gonadotoxicity of the new available targeted agents as well as to elucidate which is the best adjuvant endocrine therapy in premenopausal women with HER2-positive/hormone receptor-positive disease

Safety of Ovarian Tissue Autotransplantation for Cancer Patients

Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance

Vitrification of in vitro matured oocytes collected from antral follicles at the time of ovarian tissue cryopreservation

Background: In the past few years, cryopreservation of ovarian tissue has become an established procedure proposed in many centers around the world and transplantation has successfully resulted in full-term pregnancies and deliveries in human. This prospective study aims to evaluate the feasibility of vitrifying in vitro matured oocytes (IVM) isolated at the time of ovarian tissue cryopreservation to improve the efficiency of fertility preservation programs.Methods: Oocyte-cumulus complexes were retrieved from freshly collected ovarian cortex by aspirating antral follicular fluid, and were matured in vitro for 24-48 h prior to vitrification. Oocytes were matured in an IVM commercial medium (Copper Surgical, USA) supplemented with 75 mIU/ml FSH and 75 mIU/ml LH and vitrified using a commercial vitrification kit (Irvine Scientific, California) in high security vitrification straws (CryoBioSystem, France). Oocyte collection and IVM rates were evaluated according to the age, the cycle period and the amount of tissue collected.Results: Immature oocyte retrieval from ovarian tissue was carried out in 57 patients between 8 and 35 years of age, undergoing ovarian tissue cryopreservation. A total of 266 oocytes were isolated, 28 of them were degenerated, 200 were at germinal vesicle stage (GV), 35 were in metaphase I (MI) and 3 displayed a visible polar body (MII). The number of oocytes collected was positively correlated with the amount of tissue cryopreserved (p < 0.001) and negatively correlated with the age of the patients (p = 0.005). Oocytes were obtained regardless of menstrual cycle period or contraception. A total maturation rate of 31% was achieved, leading to the vitrification of at least one mature oocyte for half of the cohort.Conclusions: The study showed that a significant number of immature oocytes can be collected from excised ovarian tissue whatever the menstrual cycle phases and the age of the patients, even for prepubertal girls.info:eu-repo/semantics/publishe

Fertility Preservation in Female Cancer Patients

With improved survival rates among cancer patients, fertility preservation is now being recognized as an issue of great importance. There are currently several methods of fertility preservation available in female cancer patients and the options and techniques via assisted reproduction and cryopreservation are increasing, but some are still experimental and continues to be evaluated. The established means of preserving fertility include embryo cryopreservation, gonadal shielding during radiation therapy, ovarian transposition, conservative gynecologic surgery such as radical trachelectomy, donor embryos/oocytes, gestational surrogacy, and adoption. The experimental methods include oocyte cryopreservation, ovarian cryopreservation and transplantation, in vitro maturation, and ovarian suppression. With advances in methods for the preservation of fertility, providing information about risk of infertility and possible options of fertility preservation to all young patients with cancer, and discussing future fertility with them should be also considered as one of the important parts of consultation at the time of cancer diagnosis

Anti-Müllerian hormone as a marker of ovarian reserve and premature ovarian insufficiency in children and women with cancer: A systematic review

Background: Female patients undergoing anticancer treatment are at elevated risk of adverse ovarian outcomes including infertility and premature ovarian insufficiency (POI), which is associated with short- and long-term health risks. Anti-M\ufcllerian hormone (AMH) is a key biomarker of ovarian reserve, but its role prior to and after cancer treatment is less well understood. Objective and rationale: To conduct a systematic review evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment, which has become a pressing clinical issue in reproductive medicine. There are a large number of observational studies, but differences in patient groups, cancer diagnoses and study design make this a confusing field that will benefit from a thorough and robust review. Search methods: A systematic literature search for AMH in women with cancer was conducted in PubMed, Embase and Cochrane Central Register of Controlled Trials up to 1 April 2021. Bias review was conducted using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) protocol along with qualitative assessment of quality. Exploratory subgroups were established based on age, cancer type and length of follow-up. Outcomes: Ninety-two publications (N = 9183 patients) were included in this analysis after quality and bias review. Reduced/undetectable AMH was consistently identified in 69/75 studies (92%) following chemotherapy or radiotherapy, with reductions ranging from 42% to concentrations below the limit of detection, and many reporting mean or median declines of 6590%. Where longitudinal data were analysed (42 studies), a majority (33/42 (79%)) of studies reported at least partial recovery of AMH at follow-up, however, effect estimates were highly variable, reflecting that AMH levels were strongly impacted by anticancer treatment (i.e. the chemotherapy regimen used and the number of treatment cycles need), with recovery and its degree determined by treatment regimen, age and pre-treatment AMH level. In 16/31 (52%) publications, oligo/amenorrhoea was associated with lower post-treatment AMH consistent with impending POI, although menstruation and/or pregnancy were reported in patients with low or undetectable AMH. Long-term (&gt;5 years) follow-up of paediatric patients following cancer treatment also found significantly lower AMH compared with control groups in 14/20 (70%) of studies, with very variable effect sizes from complete loss of AMH to full recovery depending on treatment exposure, as in adult patients. Wider implications: AMH can be used to identify the damaging effect of cancer treatments on ovarian function. This can be applied to individual women, including pre-pubertal and adolescent girls, as well as comparing different treatment regimens, ages and pre-treatment AMH levels in populations of women. While there was evidence for its value in the diagnosis of POI after cancer treatment, further studies across a range of diagnoses/treatment regimens and patient ages are required to clarify this, and to quantify its predictive value. A major limitation for the use of AMH clinically is the very limited data relating post-treatment AMH levels to fertility, duration of reproductive lifespan or time to POI; analysis of these clinically relevant outcomes will be important in further research

Caractérisation de CRISP2 dans les spermatozoïdes humains

editorial reviewedThe Cystein-RIch Secretory Protein (CRISP) family gathers proteins recognized as key players in male fertility. Although most of the knowledge on the CRISPs comes from rodent models, three CRISPs have been identified in humans. While CRISP1 and 3 are secreted by the epididymal epithelium and associate on the surface of the spermatozoa, CRISP2 is expressed inside the spermatozoa, appearing at the round spermatid stage during spermatogenesis. However, its exact localization inside the mature spermatozoon is debated. Contrary to CRISP1 and 3, CRISP2 is thought to be non-glycosylated, but the presence of other post-translational modifications has not yet been investigated. In the present study, we contributed to the characterization of native CRISP2 in human spermatozoa. First, immunofluorescence imaging preceded by epitope retrieval allowed us to evaluate the localization of CRISP2. Then, CRISP2 was extracted from spermatozoa with various extraction buffer and analyzed by SDS-page and native-page followed by Western blot analyses to assess the presence of disulfide bonds and of CRISP2 oligomers. Finally, native CRISP2 was immunoprecipitated from sperm after capacitation (a maturation of the spermatozoa required for oocyte fertilization) to study the presence of potential post-translational modifications (PTM), in our case, phosphorylation and glycosylation

Characterization of CRISP2 in human spermatozoa

editorial reviewedThe Cystein-RIch Secretory Protein (CRISP) family gathers proteins recognized as key players in male fertility. Although most of the knowledge on the CRISPs comes from rodent models, three CRISPs have been identified in humans. While CRISP1 and 3 are secreted by the epididymal epithelium and associate on the surface of the spermatozoa, CRISP2 is expressed inside the spermatozoa, appearing at the round spermatid stage during spermatogenesis. However, its exact localization inside the mature spermatozoon is debated. Contrary to CRISP1 and 3, CRISP2 is thought to be non-glycosylated, but the presence of other post-translational modifications has not yet been investigated. In the present study, we contributed to the characterization of native CRISP2 in human spermatozoa. First, immunofluorescence imaging preceded by epitope retrieval allowed us to evaluate the localization of CRISP2. Then, CRISP2 was extracted from spermatozoa with various extraction buffer and analyzed by SDS-page and native-page followed by Western blot analyses to assess the presence of disulfide bonds and of CRISP2 oligomers. Finally, native CRISP2 was immunoprecipitated from sperm after capacitation (a maturation of the spermatozoa required for oocyte fertilization) to study the presence of potential post-translational modifications (PTM), in our case, phosphorylation and glycosylation