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Reproductive Sciences (Thousand Oaks,... Jun 2021Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including... (Review)
Review
Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including ovarian failure and infertility, in women of reproductive age. Infertility following cancer treatment can have significant adverse effects on the quality of life. However, established methods for fertility preservation, including embryo or oocyte cryopreservation, are not always suitable for female cancer patients because of complicated individual conditions and treatment methods. Ovarian tissue cryopreservation and transplantation is a promising option for fertility preservation in pre-pubertal girls and adult patients with cancer who require immediate treatment, or who are not eligible to undergo ovarian stimulation. This review introduces various methods and strategies to improve ovarian tissue cryopreservation and transplantation outcomes, to help patients and clinicians choose the best option when considering the potential complexity of a patient's situation. Effective multidisciplinary oncofertility strategies, involving the inclusion of a highly skilled and experienced oncofertility team that considers cryopreservation methods, thawing processes and devices, surgical procedures for transplantation, and advances in technologies, are necessary to provide high-quality care to a cancer patient.
Topics: Adolescent; Adult; Antineoplastic Agents; Cryopreservation; Female; Fertility Preservation; Graft Survival; Humans; In Vitro Oocyte Maturation Techniques; Infertility, Female; Neoplasms; Ovary; Radiotherapy; Stem Cells; Transplantation, Autologous; Young Adult
PubMed: 33791995
DOI: 10.1007/s43032-021-00517-2 -
Journal of Pediatric Surgery Jun 2022Pediatric intestinal failure (PIF) affects nutrition, metabolism, and endocrine development, but its downstream impact on puberty is unknown.
BACKGROUND
Pediatric intestinal failure (PIF) affects nutrition, metabolism, and endocrine development, but its downstream impact on puberty is unknown.
METHODS
A retrospective review was performed of patients age >8 years with PIF managed at an intestinal rehabilitation program. Outcomes of interest were peak height velocity (PHV), age at PHV, and age at pubertal onset (Tanner stage 2). Outcomes were stratified by sex and compared to established norms.
RESULTS
Of 110 patients with PIF, 54.5% were male. Compared to the CDC 50th percentile, PHV in PIF patients was similar for females (8.09±2.36 vs. 7.37 cm/yr;p = 0.23) but significantly higher for males (9.27±2.56 vs. 7.91 cm/yr;p = 0.038). Age at PHV in PIF patients was significantly younger for both males (12.31±2.14 vs. 13.38 years;p = 0.049) and females (10.70±1.06 vs. 11.71 years;p = 0.001). PIF patients reached pubertal onset earlier than published norms; this was significant for males (12.41±1.80 vs. 13.44 years;p = 0.014), but not for females (10.45±1.81 vs. -11.15 years;p = 0.13). The mean height-for-age Z-score was -1.2, with 20% of patients having a Z-score less than -2.
CONCLUSIONS
Pubertal onset and growth are neither delayed nor diminished in patients with PIF. The high incidence of short stature, however, highlights the importance of optimizing prepubertal linear growth to attain full height potential.
TYPE OF STUDY
Prognosis study (Retrospective cohort study).
Topics: Body Height; Child; Female; Humans; Intestinal Failure; Male; Puberty; Retrospective Studies
PubMed: 35287963
DOI: 10.1016/j.jpedsurg.2022.01.057 -
Andes Pediatrica : Revista Chilena de... Feb 2022The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this...
INTRODUCTION
The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have.
OBJECTIVE
to measure ovarian function and reserve after SCT.
PATIENTS AND METHOD
A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05.
RESULTS
41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF).
CONCLUSIONS
All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.
Topics: Adolescent; Anti-Mullerian Hormone; Child; Cross-Sectional Studies; Female; Follicle Stimulating Hormone; Hematopoietic Stem Cell Transplantation; Humans; Menopause, Premature; Ovarian Reserve; Primary Ovarian Insufficiency
PubMed: 35506772
DOI: 10.32641/andespediatr.v93i1.3693 -
Circulation Jun 2021Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for...
Suppression of Myocardial Hypoxia-Inducible Factor-1α Compromises Metabolic Adaptation and Impairs Cardiac Function in Patients With Cyanotic Congenital Heart Disease During Puberty.
BACKGROUND
Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored.
METHODS
Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies.
RESULTS
Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific -knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals.
CONCLUSIONS
In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.
Topics: Animals; Disease Models, Animal; Fatty Acids; Glucose; Glycolysis; Heart Defects, Congenital; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin Resistance; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Pioglitazone; Positron Emission Tomography Computed Tomography; Puberty; Up-Regulation; Ventricular Function, Left
PubMed: 33663226
DOI: 10.1161/CIRCULATIONAHA.120.051937 -
Orphanet Journal of Rare Diseases May 2023X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited...
BACKGROUND
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization.
METHODS
The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed.
RESULTS
Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year.
CONCLUSIONS
This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
Topics: Child; Humans; Male; East Asian People; Gonadotropin-Releasing Hormone; Hypoadrenocorticism, Familial; Hypogonadism; Mutation; Retrospective Studies; Testosterone
PubMed: 37237297
DOI: 10.1186/s13023-023-02737-y -
Journal of Animal Science Jan 2022Age at first estrus is the earliest phenotypic indicator of future reproductive success of gilts. Prebreeding anestrus is a major reason for reproductive failure leading...
Age at first estrus is the earliest phenotypic indicator of future reproductive success of gilts. Prebreeding anestrus is a major reason for reproductive failure leading to culling of replacement gilts. The two types of prebreeding anestrus are delay in attaining puberty (prepubertal anestrus, PPA) and silent ovulation (behavioral anestrus, BA). Neural tissues such as amygdala and hippocampus play a major role in regulating sexual behavior, social interactions, and receptivity to males. Differences in gene expression in the amygdala and hippocampus of gilts were analyzed in three comparisons: 1) PPA cases and cyclic controls at follicular phase of estrous cycle, 2) BA cases and cyclic controls at luteal phase of estrous cycle, and 3) gilts at different stages of the ovarian cycle (cyclic gilts at follicular phase and luteal phase of estrous cycle) to gain functional understanding of how these rarely studied tissues may differ between pubertal phenotypes and different stages of the estrous cycle of gilts. Differentially expressed genes (DEG) between PPA and BA cases and their respective cyclic controls were involved in neurological and behavioral disorders as well as nervous system functions that could directly or indirectly involved in development of behaviors related to estrus. The comparison between cyclic follicular and luteal phase control gilts identified the greatest number of DEG in the hippocampus and amygdala. These DEG were involved in adult neurogenesis and neural synapse (e.g., GABAergic, dopamine, cholinergic), suggesting that these tissues undergo structural changes and synaptic plasticity in gilts. This is the first report to demonstrate that the stage of estrous cycle is associated with dynamic changes in gene expression within porcine hippocampus and amygdala and indicates a role of gonadal steroids in regulating their biology.
Topics: Amygdala; Animals; Estrus; Female; Gene Expression; Hippocampus; Male; Progesterone; Sus scrofa; Swine
PubMed: 34984470
DOI: 10.1093/jas/skab372 -
Journal of Neuroendocrinology Apr 2022Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone...
Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n = 293 and Kallmann syndrome, n = 43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild-type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH.
Topics: Animals; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Kallmann Syndrome; Male; Mice; Mutation; Nerve Tissue Proteins; Receptors, Cell Surface
PubMed: 35170806
DOI: 10.1111/jne.13103 -
Journal of Pediatric Endocrinology &... Oct 2021Despite the high prevalence of children with sickle cell anaemia (SCA) in West Africa, there is paucity of data on the height velocity and prevalence of growth failure...
OBJECTIVES
Despite the high prevalence of children with sickle cell anaemia (SCA) in West Africa, there is paucity of data on the height velocity and prevalence of growth failure in SCA patients. With advances in clinical care of SCA patients, could there be a spatial and secular trend in the growth pattern of these children? Hence, the compelling needs to embark on this study. The objectives of the study were to determine the prevalence of growth failure among patients with SCA and its correlation with age, gender and age at diagnosis.
METHODS
A Prospective longitudinal study of a cohort of sickle cell anaemic paediatric patients from Pediatrics SCA Clinic, University of Nigeria Teaching Hospital, Ituku Ozalla. Patients were enrolled over a period of two years using a non-parametric convenient sampling method. Their heights were measured at baseline, three months, six months and at 12 months intervals and subsequently plotted on a standard WHO growth chart. The height velocities at different monthly intervals were calculated and compared with the WHO standard normal linear growth rates) for children (used as control) to identify those with GF. (i.e. <10th percentile). The main outcome measures were the mean height velocities at different months' intervals calculated and compared using the repeated measurement analysis of variance (ANOVA) and the Wilcoxon signed test.
RESULTS
A cohort of 316 children aged 1-18 years with SCA was evaluated with a male preponderance of 161 (57.4%). The mean age and age at diagnosis were 11.04 ± 5.56 and 4.2 ± 1.7 years, respectively. The prevalence of growth failure and short stature was 84.7%. The burden of GF was highest among post-pubertal participants (94.1%). The most important predictor of growth velocity deficit was age (R=0.045, standard coefficient = -0.22, =-03.51, p=0.001).
CONCLUSIONS
The study demonstrated high prevalence of growth failure in children and adolescents with SCA which intensified with advancement in age and older age at diagnosis.
Topics: Adolescent; Anemia, Sickle Cell; Body Height; Child; Child Development; Child, Preschool; Cohort Studies; Female; Humans; Infant; Longitudinal Studies; Male; Nigeria; Prevalence; Prospective Studies
PubMed: 34271599
DOI: 10.1515/jpem-2021-0232 -
Frontiers in Endocrinology 2022Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human...
BACKGROUND
Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex Growth Forum Database (Eu-IGFD) Registry (NCT00903110).
METHODS
The Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019.
RESULTS
This analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1.
CONCLUSION
Children and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.
Topics: Adolescent; Child; Clinical Studies as Topic; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Insulin-Like Growth Factor I; Male; Recombinant Proteins; Registries
PubMed: 35250870
DOI: 10.3389/fendo.2022.812568 -
International Journal of Molecular... Nov 2021Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of... (Review)
Review
Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation methods based on the patient's marital status, pubertal status, partner status, and the urgency of treatment. Widely practiced fertility preservation methods, including ovarian transposition and embryo and oocyte cryopreservation, are inappropriate for prepubertal girls or those needing urgent initiation of cancer treatment. Ovarian tissue cryopreservation and transplantation, an emerging new technology, may be a solution for these cancer patients. The use of stem cells in ovarian tissue cryopreservation and transplantation increases oxygenation, angiogenesis, and follicle survival rates. This review discusses the recent advances in ovarian tissue cryopreservation and transplantation with special focus on the use of stem cells to improve fertilization techniques.
Topics: Cryopreservation; Female; Fertility Preservation; Humans; Oocytes; Ovarian Follicle; Primary Ovarian Insufficiency; Stem Cell Transplantation; Stem Cells
PubMed: 34830363
DOI: 10.3390/ijms222212482