Deer Blood Hydrolysate Protects against D-Galactose-Induced Premature Ovarian Failure in Mice by Inhibiting Oxidative Stress and Apoptosis.

BACKGROUND: Premature ovarian failure (POF) is a common disease among women, which can cause many complications and seriously threaten women's physical and mental health. Currently, hormone replacement therapy is the primary treatment for premature ovarian failure. However, the side effects are serious and will increase the chance of breast cancer and endometrial cancer. Deer blood hydrolysate (DBH) is the product of enzymatic hydrolysis of deer blood, has antioxidant, anti-ageing, and anti-fatigue effects, and has the potential to improve premature ovarian failure. METHODS: In our experiment, a mouse model of premature ovarian failure was established through intraperitoneal injection of 400 mg/kg/d of D-gal for 42 days. At the same time, different doses of DBH were gavaged to observe its ameliorative effect on premature ovarian failure. RESULTS: The experimental findings indicated that DBH could restore the irregular oestrus cycle of POF mice, improve the abnormal amounts in serum hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), progesterone (P) and estradiol (E2), increase the number of primordial follicles and decrease the number of atretic follicles. In addition, DBH also raised the level of superoxide dismutase (SOD) and reduced the level of malondialdehyde (MDA) and reduced the apoptosis of ovarian granulosa cells in mice. The WB assay results showed that gavage of DBH restored the decrease in the indication of nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1), and B-cell lymphoma-2 (Bcl-2) proteins and reduced the elevated expression of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2 associated X protein (Bax), and Cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins that were induced by D-gal. CONCLUSIONS: To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure.

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort.

Background: The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis. Methods: The single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings. Results: The IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF. Conclusion: The study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA.

The genetic relationship between systemic lupus erythematosus and risk of primary ovarian failure from a mendelian randomization study.

Previous studies investigating the relationship between systemic lupus erythematosus (SLE) and primary ovarian failure (POF) generated conflicting results. To data, no mendelian randomization study has been applied to examine this association. In this study, genetic instruments for exposure (SLE) were selected from a GWAS study with 5201 cases and 9066 noncases. Outcome data for POF and three reproductive traits (age at menarche, age at menopause, and age at first live birth) were obtained from other eligible GWASs. To estimate causal association, the inverse-variance weighted (IVW) method (the main analyse), MR Egger test, weighted median, simple mode, and weighted mode were applied. Moreover, sensitivity analyses were conducted to ensure the robustness of the results. Estimated by the IVW method, SLE was suggested to be causally related to the risk of POF (OR = 1.166, 95% CI 1.055-1.289, P = 0.003) and delayed age at first live birth (OR = 1.006, 95% CI 1.002-1.010, P = 0.007), with no evidence of a causal association between SLE and age at menopause or menarche. The estimates were robust according to sensitivity analysis. In conclusion, the two-sample MR study supported a causal association between SLE and POF from a genetic aspect.

Tissue engineering and stem cell-based therapeutic strategies for premature ovarian insufficiency.

Premature ovarian insufficiency (POI), also known as premature ovarian failure (POF), is a complex endocrine disease that commonly affects women under the age of 40. It is characterized by the cessation of ovarian function before the age of 40, leading to infertility and hormonal imbalances. The currently available treatment options for POI are limited and often ineffective. Tissue engineering and stem cell-based therapeutic strategies have emerged as promising approaches to restore ovarian function and improve the quality of life for women affected by POI. This review aims to provide a comprehensive overview of the types of stem cells and biomaterials used in the treatment of POI, including their biological characteristics and mechanisms of action. It explores various sources of stem cells, including embryonic stem cells, induced pluripotent stem cells, and adult stem cells, and their potential applications in regenerating ovarian tissue. Additionally, this paper discusses the development of biomaterials and scaffolds that mimic the natural ovarian microenvironment and support the growth and maturation of ovarian cells and follicles. Furthermore, the review highlights the challenges and ethical considerations associated with tissue engineering and stem cell-based therapies for POI and proposes potential solutions to address these issues. Overall, this paper aims to provide a comprehensive overview of the current state of research in tissue engineering and stem cell-based therapeutic strategies for POI and offers insights into future directions for improving treatment outcomes in this debilitating condition.

Ketosis-prone Diabetes and Hypogonadism: A New Clinical Association to be Aware of ?

BACKGROUND: Ketosis-prone diabetes (KPD) is an emerging entity, sharing features of both type 1 diabetes mellitus and type 2 diabetes mellitus. Patients with KPD usually present with diabetic ketoacidosis without the classic phenotype of autoimmune type 1 diabetes. In most cases, they are Afro-American adults, who require insulin therapy for the management of acute decompensation, then usually encountering insulin-free remission for prolonged periods of time with diet or with non-insulin agents. Meanwhile, hypogonadism is a known condition that could be associated with higher risk of developing both type 1 and type 2 diabetes and could be a risk factor for decompensated diabetes. The association of KPD and hypogonadism is reported for the first time in literature. CASE PRESENTATION: Here we report two peculiar cases of young African patients, affected by KPD and hypergonadotropic hypogonadism, respectively Klinefelter's syndrome and primary ovarian failure. Both patients were treated promptly for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. After the correct clinical evaluation, oral antidiabetic drugs were added. CONCLUSION: KPD remains an under-recognized and under-diagnosed type of diabetes. As hypogonadism is strongly linked to dysmetabolic disorders, the evaluation of sex hormones should be performed at the onset of diabetes. Further studies should investigate the hypothalamic-pituitary-gonadal axis and its role in the development of KDP and its manifestations and complications.

Long-Term Effect on Ovarian Function After Uterine Artery Embolization During the Postpartum Period: A Nationwide Population-Based Study.

Uterine artery embolization(UAE) is widely used in obstetrical indications, including postpartum bleeding and placental implantation abnormality, to manage many conditions to conserve the uterus. However, physicians are concerned about future fertility or ovarian function due to the occlusion of major pelvic vessels in the uterine artery embolization. However, there are limited data related to UAE usage during the postpartum period. This study was to evaluate the impact of UAE during the postpartum period on primary ovarian failure(POF), menstrual disorders, and infertility in women. Using the Korea National Health Insurance claims database, all pregnant women who delivered between January 2007 and December 2015 and underwent UAE during the postpartum period were identified. The occurrence of POF, female infertility, and menstrual disorders after delivery was evaluated. Using Cox proportional hazards models, the adjusted hazard ratios and 95% confidence intervals were estimated. 779,612 cases were analyzed in the study with 947 women in the UAE group. After delivery, the incidence of POF (0.84% vs.0.27%, P<.0001) and female infertility (10.24% vs. 6.89%, P<.0001) were higher in UAE group than in the control group. After adjusting for covariates, the POF risk was significantly higher in UAE group than in the control group (HR 2.37, 95% CI 1.16-4.82). The risk for the disorder of menstrual frequency (HR 1.28, 95% CI 1.10-1.50) and female infertility (HR 1.37, 95% CI 1.10-1.71) was significantly higher in UAE group than in the control group. This study confirmed UAE during the postpartum period is a risk factor for POF after delivery.

Meiotic Chromosome Structure, the Synaptonemal Complex, and Infertility.

In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome axes. The mammalian SC comprises at least eight largely coiled-coil proteins that interact and self-assemble to generate a long, zipper-like structure that holds homologous chromosomes in close proximity and promotes the formation of genetic crossovers and accurate meiotic chromosome segregation. In recent years, numerous mutations in human SC genes have been associated with different types of male and female infertility. Here, we integrate structural information on the human SC with mouse and human genetics to describe the molecular mechanisms by which SC mutations can result in human infertility. We outline certain themes in which different SC proteins are susceptible to different types of disease mutation and how genetic variants with seemingly minor effects on SC proteins may act as dominant-negative mutations in which the heterozygous state is pathogenic.

Novel STAG3 variant associated with primary ovarian insufficiency and non-obstructive azoospermia in an Iranian consanguineous family.

Non-obstructive azoospermia (NOA) and primary ovarian insufficiency (POI) present the most severe forms of male and female infertility. In the last decade, the increasing use of whole exome sequencing (WES) in genomics studies of these conditions has led to the introduction of a number of novel genes and variants especially in meiotic genes with restricted expression to gonads. In this study, exome sequencing of a consanguineous Iranian family with one POI and two NOA cases in three siblings showed that all three patients were double homozygous for a novel in-frame deletion and a novel missense variant in STAG3 (NM_001282717.1:c.1942G > A: p.Ala648Thr; NM_001282717.1:c.1951_1953del: p. Leu652del). Both variants occur within a short proximity of each other affecting the relatively conserved armadillo-type fold superfamily feature. STAG3 is a specific meiotic cohesin complex component that interacts with the α-kleisin subunit through this feature. Protein homology modeling indicated that the in-frame deletion destabilizes kleisin biding by STAG3. Although the missense variant did not seem to affect the binding significantly, protein homology modeling suggests that it further destabilizes kleisin binding when in double homozygous state with the deletion. Our findings are in line with several other studies having associated deleterious variants affecting this region with male and female infertility in humans and mouse models. This is the first report associating an in-frame STAG3 variant with NOA and POI in a single family. SUMMARY SENTENCE: A patient with primary ovarian failure and her two brothers with non-obstructive azoospermia were double homozygous for a novel in-frame deletion and a novel missense variant in STAG3 that potentially disrupt the protein's meiotic functions.

Characterization of a novel mutation V136L in bone morphogenetic protein 15 identified in a woman affected by POI.

BACKGROUND: Premature ovarian insufficiency (POI) is an ovarian defect characterized by primary or secondary amenorrhea, hypergonadotropism and hypoestrogenism which occurs before the age of 40 years with a major genetic component. In this study we performed clinical evaluation and genetic analysis of a group of 18 patients with POI. The study involved 18 consecutive women with POI. Karyotiping and genetic analysis for research of mutations in GDF9 (Growth Differentation Factor 9) and BMP15 (Bone morphogentic protein 15) genes and FMR1 (Fragile X Mental Retardation 1) premutation were carried out. In vitro functional study of the novel BMP15 mutation was performed using COV434 (Human ovarian granulosa tumour cells 434) cells of ovarian granulosa, which consistently express BMP responsive element, and luciferase reporter assay. RESULTS: Three patients (17%) had a family history of POI. Ten patients (56%) had a family history of autoimmune diseases and nine patients (50%) showed a personal history of one or more autoimmune diseases. Of patients for whom morphological assessment was available, almost half (44%) had poor follicle assets or small ovaries's size at pelvic US. Two patients (13%) showed reduced bone density at DEXA (Dual Energy X-ray Absorptiometry). All the women had normal female kariotype and no mutations in the GDF-9 gene or FMR1 premutations were found. A novel heterozygous mutation c.406G > C (V136L) of BMP15 gene was identified in one patient. After transfection in COV434 cells, BMP15 variant showed a significantly reduced luciferase activity compared to wild type. CONCLUSIONS: POI is a multifactorial disease with several health implications. Autoimmunity and genetics represent the most common aetiology. We identified and characterized a novel BMP15 mutation, providing an additional elucidation of molecular basis of this complex disorder.

Laparoscopic assisted extracorporeal ovarian harvest: A novel technique to optimize ovarian tissue for cryopreservation in young females with cancer.

BACKGROUND: Advances in pediatric cancer therapy have improved the long-term survival for many children with cancer. The awareness of quality of life aspects, specifically fertility preservation, has become a reality for many of these families and children. Ovarian tissue cryopreservation has emerged as an available fertility option for young females with cancer. Safe and effective removal of ovarian tissue in these girls is paramount. We report a laparoscopic assisted extracorporeal ovarian harvest technique that achieves this goal. OPERATIVE TECHNIQUE: We place a 5 mm port at the umbilicus and in the right lower quadrant. Under laparoscopic guidance we place a 12 mm port in the left suprapubic area. Utilizing the 12 mm port site a monofilament traction suture is placed through the left ovary. The traction suture is used to translocate the ovary to an extracorporeal position via the 12 mm port site. Ovarian tissue is then excised utilizing standard surgical technique with the scalpel. Hemostasis is obtained and the capsule is closed with a running absorbable suture. The ovary is placed back in its native position laparoscopically. CONCLUSIONS: The use of this extracorporeal ovarian harvesting technique is a safe and effective method to optimize removal and minimize tissue injury. Utilization of this technique, may have potential benefit to the young female with cancer.

A Novel Mutation in the FSH Receptor (I423T) Affecting Receptor Activation and Leading to Primary Ovarian Failure.

CONTEXT: Follicle-stimulating hormone (FSH) plays an essential role in gonadal function. Loss-of-function mutations in the follicle-stimulating hormone receptor (FSHR) are an infrequent cause of primary ovarian failure. OBJECTIVE: To analyze the molecular physiopathogenesis of a novel mutation in the FSHR identified in a woman with primary ovarian failure, employing in vitro and in silico approaches, and to compare the features of this dysfunctional receptor with those shown by the trafficking-defective D408Y FSHR mutant. METHODS: Sanger sequencing of the FSHR cDNA was applied to identify the novel mutation. FSH-stimulated cyclic adenosine monophosphate (cAMP) production, ERK1/2 phosphorylation, and desensitization were tested in HEK293 cells. Receptor expression was analyzed by immunoblotting, receptor-binding assays, and flow cytometry. Molecular dynamics simulations were performed to determine the in silico behavior of the mutant FSHRs. RESULTS: A novel missense mutation (I423T) in the second transmembrane domain of the FSHR was identified in a woman with normal pubertal development but primary amenorrhea. The I423T mutation slightly impaired plasma membrane expression of the mature form of the receptor and severely impacted on cAMP/protein kinase A signaling but much less on ß-arrestin-dependent ERK1/2 phosphorylation. Meanwhile, the D408Y mutation severely affected membrane expression, with most of the FSH receptor located intracellularly, and both signal readouts tested. Molecular dynamics simulations revealed important functional disruptions in both mutant FSHRs, mainly the loss of interhelical connectivity in the D408Y FSHR. CONCLUSIONS: Concurrently, these data indicate that conformational differences during the inactive and active states account for the distinct expression levels, differential signaling, and phenotypic expression of the I423T and D408Y mutant FSHRs.

Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population.

Premature ovarian failure (POF) is a complex disease of which the etiology is influenced by numerous genetic variations. Several POF candidate genes have been reported. However, no causal genes with high odds ratio (OR) have yet been discovered. This study included 564 females of Korean ethnicity, comprising 60 patients with POF and 182 controls in the discovery set and 105 patients with POF and 217 controls in the replication set. We conducted genome-wide association analysis to search for novel candidate genes predicted to influence POF development using Axiom Precision Medicine Research Arrays and additive model logistic regression analysis. One statistically significant single nucleotide polymorphism (SNP), rs55941146, which encodes a missense alteration (Val > Gly) in the APBA3 gene, was identified with OR values for association with POF of 13.33 and 4.628 in the discovery and replication sets, respectively. No rs55941146 minor allele homozygotes were present in either cases or controls. The APBA3 protein binds FIH-1 that inhibits hypoxia inducible factor-1α (HIF-1α). HIF-1α contributes to granulosa cell proliferation, which is crucial for ovarian follicle growth, by regulating cell proliferation factors and follicle stimulating hormone-mediated autophagy. Our data demonstrate that APBA3 is a candidate novel causal gene for POF.

Effect of human amniotic epithelial cells on ovarian function, fertility and ovarian reserve in primary ovarian insufficiency rats and analysis of underlying mechanisms by mRNA sequencing.

Human amniotic epithelial cells (hAECs) show similar features to stem cells and have low immunogenicity. This study aims to investigate the therapeutic effect of hAEC transplantation on cyclophosphamide-induced primary ovarian insufficiency (POI) rats and evaluate the underlying mechanisms by mRNA sequencing of ovarian samples. Notably, hAECs mainly located in the interstitial area of the ovaries rather than follicles. hAEC transplantation led to a slight increase in body and ovary weight, normalized irregular estrous cycles, decreased serum follicle stimulating hormone (FSH) and increased anti-Mullerian hormone (AMH) level and restored follicle pools in POI rats. Ovarian expression of AMH, follicle stimulating hormone receptor (FSHR) and klotho in POI rats was also significantly upregulated following hAEC transplantation. Fetus number was higher in the hAEC transplantation group than the POI group. The mRNA sequencing results showed that hAEC transplantation led to the upregulation of several angiogenesis and inflammation molecules including interferon regulatory factor 7 (IRF7), Mx dynamin-like GTPase 1 (Mx1), vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2. Moreover, hAEC therapy had an effect on ribosomes, protein digestion, protein absorption, neuroactive ligand-receptor interaction, cAMP signaling pathway and steroid biosynthesis pathways. The expression of several steroid biosynthesis proteins was significantly upregulated as measured by quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemical staining and Western blot analysis. In summary, hAECs can significantly restore ovarian function, and improve both ovarian reserve and fertility. This may be due to the paracrine effect of hAECs in regulating steroid biosynthesis, modulating follicle development from initiation to ovulation, promoting angiogenesis and reducing inflammation.

Changes in the vaginal microbiota associated with primary ovarian failure.

BACKGROUND: Primary ovarian failure (POF) is defined as follicular failure in women of reproductive age. Although many factors are speculated to contribute to the occurrence of POF, the exact aetiology remains unclear. Moreover, alterations in the microbiome of patients with POF are poorly studied. RESULTS: This study investigated the vaginal microbiota of 22 patients with POF and 29 healthy individuals. High-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to evaluate the relationships between the vaginal flora and clinical characteristics of POF. Different from results of previous studies, we found that the diversity and richness of the vaginal flora of patients with POF was significantly different from those of healthy controls. Comparison of the vaginal flora of patients with POF with that of menopausal women revealed that the relative abundance of Lactobacillus was significantly reduced in the latter. A reduced abundance of Lactobacillus was furthermore associated with a lower pregnancy success rate. Of particular interest is that L. gallinarum especially appeared to be beneficially associated with reproductive-related indicators (FSH, E2, AMH, PRL) whilst L. iners appeared to have a detrimental effect. The result of the present study may enable the identification of microbiota associated with POF, however, further investigations of differences in the microbiota in the context of POF will enable a deeper understanding of the disease pathogenesis that involves modification of the vaginal microbiota. CONCLUSIONS: The present study identified the microbiota associated with POF. Further investigations on the differences in the microbiota in the context of POF will improve our understanding of the pathogenesis of the disease which involves modification of the vaginal microbiota.

Primary amenorrhea in females attending gynaecological outpatient of a tertiary care hospital at Peshawar.

OBJECTIVE: To determine the aetiological factors of amenorrhea. METHODS: The pilot cross-sectional study was conducted in Government Naserullah Khan Babar Memorial Hospital, Peshawar, Pakistan, from January 2015 to December 2017, and comprised amenorrhea cases. Cases were analysed according to their clinical profile, ultrasound findings and biochemical tests. Data was analysed using SPSS 20. RESULTS: There were 100 patients with a mean age of 22.17±5.52 years (range: 14-36 years). Anatomical defects were the most common cause in 60(60%) patients. Imperforate hymen and transverse vaginal septum were found in 7(7%), 7(7%) patients each, while mullerian abnormalities were found in 46(46%) patients. Hypergonadotropic hypogonadism and polycystic ovarian syndrome were found in 17(17%) patients each. CONCLUSIONS: Anatomical defects were found to be the most common cause among amenorrhea patients.

Protective effect of alpha lipoic acid on 4-vinylcyclohexene diepoxide induced primary ovarian failure in female rats.

OBJECTIVE: The effects of alpha lipoic acid (ALA) and its possible mechanisms in treating Primary ovarian failure (POF) model was studied with 4 vinylcyclohexene diepoxide (VCD). MATERIAL AND METHODS: Rats were divided into 4 groups (n = 7) as Control, VCD, VCD + ALA and ALA. POF model was induced by applying VCD intraperitoneally and ALA was administered by oral gavage as 100 mg/day to the VCD + ALA and ALA groups. RESULTS: At the end of 42 days, ovarian and uterine tissues were received. The number of primordial and primary follicles were increased and corpus luteum and cystic follicles were decreased in ovarian tissues in VCD + ALA group compared to VCD group. Caspase-3 immunoreactivity in follicular cells was decreased in VCD + ALA group compared to VCD group. eNOS immunoreactivity and eNOS levels were decreased in VCD group and increased in VCD + ALA group while iNOS immunoreactivity and iNOS levels were increased in VCD group, decreased in VCD + ALA group in ovary and uterine tissue. Plasma FSH and LH hormone levels were increased in the VCD but decreased in VCD + ALA group. Estradiol level decreased in the VCD group compared to the other groups. The MDA values were significantly increased in the VCD + ALA group compared to VCD group. In addition, the levels of GSH values were decreased in VCD + ALA group compared to VCD group. CONCLUSION: Alpha lipoic acid treatment of rats with VCD-induced POF had a beneficial effect on reducing ovarian damage by improving histological, immunohistochemical, hormone level and oxidative stress markers. Our results show that ALA is an effective treatment of VCD-induced POF rats.

Oral oyster polypeptides protect ovary against d-galactose-induced premature ovarian failure in C57BL/6 mice.

BACKGROUND: Oyster polypeptides have various biofunctions, such as anti-cancer and anti-oxidative stress, but whether it has the protective effects to primary ovarian failure (POF) remains poorly understand. To address this issue, daily gavage of oyster polypeptides was performed to investigate their protective effect, basing on d-galactose-induced POF model in C57BL/6 female mice. RESULTS: Oyster polypeptides restored the irregular estrous cycles and the abnormal serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P) levels as well as the decreased mRNA expression level of Amh that were induced by d-galactose. The follicle development of POF mice was improved by increasing the primordial follicle ratio and decreasing the atretic follicle number after oral administration of oyster polypeptides. Moreover, in the oyster polypeptides treated mice, the total superoxide dismutase (T-SOD) activity was significantly increased, while the malondialdehyde levels were significantly decreased. The mRNA expression levels of stress-related genes (SOD2, SIRT1 and FOXO3a) were remarkably up-regulated after d-galactose induction, but the up-regulation was weakened or disappeared by the gavage of oyster polypeptides. In addition, oyster polypeptides treatment also reduced the apoptosis of the ovarian granulosa cells and down-regulated the mRNA expression levels of apoptosis-related genes (p53 and Bad but not Bcl-2). CONCLUSION: This study reveals that oyster polypeptides may protect ovary against d-galactose-induced POF by their anti-oxidative stress activity to rescue d-galactose-induced ovarian oxidative damage and therefore to prevent ovarian cells apoptosis, thereby tipping the abnormality trigged by POF to get close to the normal levels. © 2019 Society of Chemical Industry.

POI after chemotherapy and bone marrow transplant may mimic disorders of sexual differentiation - a case report of a patient with primary amenorrhea and 46, XY karyotype.

Cytogenetic examination may be useful in determining the reason for primary amenorrhea in phenotypically female patients. The result 46, XY usually indicates two syndromes: complete androgen insensitivity or pure gonadal dysgenesis. We report a case of a patient, who due to acute lymphoblastic leukemia in childhood was treated with total body irradiation and bone marrow transplantation. Later on the patient presented with symptoms typical for premature ovarian failure and male karyotype in peripheral lymphocytes. The cytogenetic examination for peripheral cells showed normal female karyotype. Therefore, it has been concluded that ovarian function impairment resulted rather from the gonadotoxic effect of oncological treatment than as a disorder of sexual differentiation. The survival rates of childhood cancer are very high and some of the patients will experience premature ovarian failure. It must be remembered that after bone marrow transplantation karyotype of peripheral lymphocytes may be misleading.

Amenorrea primaria asociada a paciente con cariotipo 45 XX, ROB (13; 14) (q 10; q 10): presentación de un caso / Primary amenorrhea associated with a patient with karyotype 45 XX, ROB (13; 14) (q 10; q 10): case presentation

La función ovárica depende de la expresión de múltiples genes, por lo que las anomalías del cromosoma X y los autosomas revisten gran importancia en la etiología de la insuficiencia ovárica primaria (IOP). Las translocaciones de autosomas en mujeres con IOP son muy raras y solo se han detectado tres casos: dos translocaciones entre los cromosomas 2 y 15 en dos mujeres con cariotipo 46, XX, t (2, 15) (q32.3, q13.3)2; una translocación entre los cromosomas 13 y 14 en una mujer con cariotipo 45, XX, t (13; 14)3; por lo que nuestro caso sería el cuarto reporte de mujeres con translocaciones de autosomas e IOP.

Ovarian function depends on the expression of multiple genes, so Xchromosome abnormalities and autosomes are of great importance in the etiology of primary ovarian insufficiency (IOP). Autosomal translocations in women with IOP are very rare and only three cases have been detected: two translocations between chromosomes 2 and 15 in two women with karyotype 46, XX, t (2, 15) (q32.3, q13.3)2; a translocation between chromosomes 13 and 14 in a woman with karyotype 45, XX, t (13; 14)3 , so our case would be the fourth report of women with autosomal translocations and IOP.

Perfil clínico y epidemiológico de la insuficiencia ovárica primaria en la consulta endocrino-ginecológica de dos instituciones de salud de Medellín, Colombia / Clinical and epidemiological profile of primary ovarian failure in gynecological endocrine consultation in two health institutions in the city of Medellin, Colombia

Resumen OBJETIVO: Determinar el perfil clínico y epidemiológico de las pacientes con insuficiencia ovárica primaria atendidas en la consulta endocrino-ginecológica de dos instituciones de salud de Medellín, Colombia. MATERIALES Y MÉTODOS: Estudio descriptivo, transversal y retrospectivo efectuado en pacientes con insuficiencia ovárica primaria atendidas en la consulta médica de endocrinología entre 2017 y 2018. Para el análisis se calcularon frecuencias absolutas y relativas para las variables cualitativas, para las cuantitativas, mediana. RESULTADOS: Se incluyeron 25 pacientes con edad promedio de 32.9 años. La edad promedio a la menarquia y amenorrea definitiva fue de 12.05 años y 28.5 años, respectivamente. Alrededor de los 28.7 años recibieron el diagnóstico; la menor y mayor edad al diagnóstico fue de 13 y 42 años, respectivamente. Se encontró que 21 de 25 pacientes tuvieron amenorrea secundaria, 14 de 25 ciclos regulares. Los síntomas más frecuentes fueron: bochornos en 11 de 25, 8 de 25 sudoración y 5 de 25 depresión. CONCLUSIONES: Las pacientes con insuficiencia ovárica primaria tienen un perfil clínico sumamente variable en cuanto a evolución de la enfermedad; sin embargo, casi todas las de este estudio tuvieron coincidencia en síntomas y signos. Es importante que se efectúen más estudios a este respecto que permitan ampliar la información epidemiológica local y nacional.

Abstract OBJECTIVE: To determine the clinical and epidemiological profile of primary ovarian failure in gynecological endocrine consultation in two health institutions in the city of Medellin. MATERIALS AND METHODS: retrospective cross-sectional descriptive study, in which the study population were adult women with primary ovarian failure who attended the endocrinological medical consultation from 2017 to 2018. The source of the information were clinical histories of patients with primary ovarian failure who attended this consultation. For the analysis, absolute and relative frequencies were calculated for the qualitative variables, for the quantitative ones, the median was used. RESULTS: twenty-five women who met the eligibility criteria were included; The average age of the patients was 32.96 years. The mean age of menarche and definitive amenorrhea of the patients was 12.05 years and 28.57 years respectively, at approximately 28.73 years of age, the patients were diagnosed with primary ovarian insufficiency, the lowest and highest age of diagnosis was at 13 and 42 years respectively. 21/25 patients had secondary amenorrhea, 14/25 of the patients had regular cycles. The most common symptoms were heats 11/25, sweating (8/25) and depression (5/25). CONCLUSIONS: Women with primary ovarian failure had a clinical profile with wide variation regarding the development of the disease, however, they match in most symptoms and signs. It's important to continue studying and expanding the information about epidemiology in national and international context.