Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation.

Women are born with a non-renewable pool of ovarian follicles, referred to as the ovarian reserve. This reserve consists of primordial follicles in the ovaries and can be affected by many factors, such as genetic and endocrine disorders, medical interventions, and endocrine disruptors. Fertility preservation is recommended when gonadotoxic treatments are necessary.

Longitudinal trends in testicular volume z scores from puberty to adulthood, sperm quality, and paternity outcomes after childhood cancer.

Background: Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood.

Methods: The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964-2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n = 38), 14 years (n = 57), 16 years (n = 63), 18 years (n = 105), and in adulthood (n = 43; median age, 27 years).

Imatinib decreases germ cell survival and germline stem cell proliferation in rodent testis ex vivo and in vitro.

Background: Imatinib and dasatinib are tyrosine kinase inhibitors (TKIs) increasingly used to treat several diseases in both children and adults at fertile age. We have previously shown that imatinib has adverse effects on developing testis, and imatinib-treated male patients have been reported to have reduced sperm counts. However, the cellular level effects of imatinib and dasatinib on adult male germ cells and germline stem cells (mGSCs) have not been thoroughly investigated.

Factors Influencing the Timing of Ovarian Tissue Cryopreservation in Young Girls.

The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedure and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility. The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments.

Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients.

Study Question: Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?

Summary Answer: Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.

What Is Known Already: Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples.

How to manage patients with germline variants: Recommendations from the Nordic working group on germline predisposition for myeloid neoplasms.

Increasing recognition of germline variants in patients with hematological malignancies prompted us to provide -specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%-5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline variant, while half of them acquire a somatic second hit in the other allele.

A 12-year overview of fertility preservation practice in Nordic pediatric oncology centers.

Purpose: Fertility preservation is the only option to safeguard fertility following gonadotoxic treatments. This study aimed to provide an updated status on fertility preservation for pediatric cancer patients in the Nordic countries.

Methods: A questionnaire consisting of 14 questions was sent to directors of 18 main pediatric oncology centers in the Nordic countries in 2010 and 2022.

Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT.

Management of hyperleukocytosis in pediatric acute myeloid leukemia using immediate chemotherapy without leukapheresis: results from the NOPHO-DBH AML 2012 protocol.

Hyperleukocytosis in pediatric acute myeloid leukemia (AML) is associated with severe complications and an inferior outcome. We report results on patients with hyperleukocytosis included in the NOPHO-DBH AML 2012 study. We recommended immediate initiation of full-dose chemotherapy (etoposide monotherapy for 5 days as part of the first course), avoiding leukapheresis and prephase chemotherapy.

Efficacy of a web-based psychoeducational intervention, Fex-can sex, for young adult childhood cancer survivors with sexual dysfunction: A randomized controlled trial.

Background: No web-based interventions addressing sexual problems are available for young adult survivors of childhood cancer.

Aim: This study aimed to test the efficacy of a web-based psychoeducational intervention, Fex-Can Sex, to alleviate sexual problems in young adults treated for cancer during childhood.

Method: This randomized controlled trial tested the effects of a 12-week, self-help, web-based intervention.

Mitoxantrone Versus Liposomal Daunorubicin in Induction of Pediatric AML With Risk Stratification Based on Flow Cytometry Measurement of Residual Disease.

Purpose: Measurable residual disease (MRD) by using flow cytometry after induction therapy is strongly prognostic in pediatric AML, and hematopoietic stem-cell transplant (hSCT) may counteract a poor response. We designed a phase III study with intensified response-guided induction and MRD-based risk stratification and treated poor induction response with hSCT. The efficacy of liposomal daunorubicin (DNX) in induction was compared with mitoxantrone.

Pubertal testicular volume references for ruler, orchidometer, and ultrasonography measurements based on a longitudinal follow-up.

Background: Testicular volume is a marker of male pubertal development. Various clinical conditions and their treatments may influence testicular growth.

Objectives: To create ruler-based age-dependent pubertal testicular volume references that enable calculation of standard deviation (SD) scores.

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey.

Study Question: Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue?

Summary Answer: Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding.

What Is Known Already: For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility.

Reproductive late effects and testosterone replacement therapy in male childhood cancer survivors: A population-based study (the Fex-Can study).

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects.

Reference standards for follicular density in ovarian cortex from birth to sexual maturity.

Research Question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?

Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean ± SD 11 ± 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.

Results: No difference was observed between Z-scores in samples from untreated patients (0.

Therapeutic exposures and pubertal testicular dysfunction are associated with adulthood milestones and paternity after childhood cancer.

Background: Childhood cancer therapy may cause long-term effects. This cross-sectional study evaluated adulthood milestones in male childhood cancer survivors (CCS).

Methods: The study population comprised 252 male CCS with 6 to 42 years of survival diagnosed at the Children's Hospital in Helsinki (1964-2000) at the age of 0 to 17 years.

Premature ovarian insufficiency and chance of pregnancy after childhood cancer: A population-based study (the Fex-Can study).

Endocrine complications are a common late effect after childhood cancer. Our study assessed the prevalence and predictors of premature ovarian insufficiency (POI) and prospects of pregnancy in young female survivors. This nationwide study combined registry and survey data for female childhood cancer survivors aged 19 to 40 years, identified through the National Quality Registry for Childhood Cancer in Sweden.

The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia.

Biallelic germ line excision repair cross-complementing 6 like 2 (ERCC6L2) variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies, characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germ line variants collected retrospectively from 11 centers globally, with a follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM).

The Effect of Blood Transfusion on the Survival of Children with Both Severe Anemia and Bacterial Meningitis.

In areas with suboptimal resources, blood transfusion may not be feasible even when mandatory for severely anemic children with a life-threatening disease. We evaluated how much not having received a transfusion affected the survival in 171 children with an admission blood hemoglobin level of < 6 g/dL and bacterial meningitis in Luanda, Angola. Of these children, 75% (128 of 171) had received a blood transfusion during hospitalization, but 25% (43 of 171) had not.