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Aim Methods Results Conclusion To evaluate the causes and clinical characteristics of primary amenorrhea and ovarian or gonadal disorders in women.The medical records of all women evaluated for primary amenorrhea between January 2002 and December 2023 were retrospectively reviewed. Women with missing data were excluded from the study. Disorders of the ovary or gonads (hypergonadotropic hypogonadism) were defined as increased serum follicle‐stimulating hormone (FSH) levels (>40 mIU/mL).Over a 21‐year period, after excluding 1 woman with incomplete data, the study included 87 women who met the inclusion criteria. The median age at presentation was 18 years (interquartile range [IQR], 17–20). The median estradiol level was 5 pg/mL (IQR 5–10.4), and the median FSH level was 80 mIU/mL (IQR 63.1–94.9). The most common cause of primary amenorrhea was Turner syndrome (TS), followed by 46,XX and 46,XY gonadal dysgenesis. The median height was 147 cm (IQR, 140–158.7), and 50 women (57.5%) had karyotypic abnormalities, with TS being the most common abnormality.TS was identified as the most common cause of primary amenorrhea with ovarian or gonadal disorders. [ABSTRACT FROM AUTHOR]

Background: Restoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement. Methods: Human umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment. Results: After culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel. Conclusions: Our study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure. [ABSTRACT FROM AUTHOR]

Abstract Background Restoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement. Methods Human umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment. Results After culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel. Conclusions Our study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure.

In-vitro maturation (IVM) is the process of cultivating early-stage follicles from the primordial to the antral stage and facilitating the maturation of oocytes outside the body within a supportive environment. This intricate procedure requires the careful coordination of various factors to replicate the natural ovarian conditions. Advanced techniques for IVM are designed to mimic the natural ovarian environment and enhance the development of follicles. Three-dimensional (3D) culture systems provide a more biologically relevant setting for follicle growth compared to traditional two-dimensional (2D) cultures. Traditional culture systems, often fail to support the complex process of follicle development effectively. However, modern engineered reproductive tissues and culture systems are making it possible to create increasingly physiological in-vitro models of folliculogenesis. These innovative methods are enabling researchers and clinicians to better replicate the dynamic and supportive environment of the ovary, thereby improving the outcomes of IVM offering new hope for fertility preservation and treatment. This paper focuses on the routine 3D culture, and innovative 3D culture of ovary and follicles, including a tissue engineering scaffolds, microfluidic (dynamic) culture system, organ-on-chip models, EVATAR system, from a clinical perspective to determine the most effective approach for achieving in-vitro maturation of follicles. These techniques provide critical support for ovarian function in various ovarian-associated disorders, including primary ovarian insufficiency (POI), premature ovarian failure (POF), ovarian cancer, and age-related infertility. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced amenorrhea (CIA) is a surrogate for ovarian failure, which is indicative of ovarian failure in young females taking chemotherapy. The CIA lacks sufficient reproducibility and reliability. Our aim is to assess the anti-Mullerian hormone (AMH) concentrations before and after chemotherapy (CTh) for premenopausal female patients with breast cancer and to correlate AMH values with menopausal status post-CTh. Methods: This Prospective cohort study was conducted on 100 subjects at the Medical Oncology Department, Faculty of Medicine, Zagazig University. Pre-menopausal condition is characterized as two or more menstrual cycles in the 120 days before the start of CTh in females aged 18 to 45 years. The following data were obtained from the patient's sheets: patient history, clinical data, and AMH, estrogen, follicular stimulating hormone (FSH), and luteinizing hormone (LH) concentrations were assessed at baseline. Following blood tests were done after the end of the final cycle of CTh. Results: Our study showed a statistically significant difference between baseline and post-chemotherapy hormonal biomarkers (P <0.05). AMH levels were significantly decreased from(2.97 ±1.94) to (0.47 ±0.74) post-chemotherapy, and it is a sensitive prediction biomarker for ovarian failure induced by chemotherapy. There was a significant negative correlation between baseline AMH with BMI (P<0.001). Conclusions: Serum AMH is a sensitive prediction biomarker of ovarian failure induced by chemotherapy, comparable with FSH, LH, and Estradiol levels. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). Methods: This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein–protein interaction network and functional enrichment analysis were performed using the STRING database. Results: The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p <.0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p <.0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). Conclusion: The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval. [ABSTRACT FROM AUTHOR]

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish (Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress. [ABSTRACT FROM AUTHOR]

AbstractObjective To assess the impacts of Platelet-Rich Plasma(PRP) and Granulocyte Colony-Stimulating Factor(G-CSF) on a rat model with induced ovarian follicular damage caused by cyclophosphamide(Cy).Materials and Methods Forty-two Sprague–Dawley rats were randomly allocated into seven distinct groups as; Group 1(control): NaCl intraperitoneal (IP) injection was administered on days D1, D7, and D14. Group 2(Cy):Cy IP injection on D1 + NaCl IP injection on D7 and D14 were administered. Group 3(PRP): PRP IP injection on D1,D7 and D14 were administered. Group 4(Cy + PRP):Cy IP injection on D1 and PRP IP injection on D1, D7 and D14 were administered. Group 5(G-CSF): G-CSF IP injection on D1, D7 and D14 were administered. Group 6(Cy + G-CSF):Cy IP injection on D1+ G-CSF IP injection on D1, D7 and D14 were administered. Group 7(Cy + PRP + G-CSF):Cy IP injection on D1+ PRP IP injection on D1,D7 and D14+ G-CSF IP injection on D1,D7 and D14 were administered. Follicular number, histological scores of AMH and INSL3 stained follicles at different stages of follicular development, and serum Anti-Müllerian hormone(AMH) were evaluated.Results The primary, secondary, and antral follicle intensity scores for AMH-positive staining were most prominent in Groups 3 and 5. There was no significant difference between groups 4, 6 and 7 compared to group 1 in terms of follicule counts and AMH staining. The intensity scores of AMH-positive staining follicles were notably reduced in group 2 compared to groups 4, 6, and 7, with a significant difference (p

Background In cases of ovarian failure due to malnutrition, stem cell therapy is ineffective due to the lack of viability and differentiation of transplanted cells, resulting in low adaptation and survival rates. This study aimed to investigate whether stem cells cultured under low oxygen (O 2) tension improve the adaptability and viability of cells in rats with ovarian failure. Methods After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O 2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C− groups, respectively. Results The slight increase gradually in cells expressing HSP70, VEGF-1, and GDF-9 was reported in C+, T2, T1, and C− groups, respectively. Caspase-3 expression was reported to decrease gradually in C+, T2, T1, and C− groups. Meanwhile, Graafian follicle count was reported to increase gradually in C+, T2, T1, and C− groups, respectively. Conclusions Based on those parameters, MSCs cultured under low O 2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure.

Premature ovarian insufficiency (POI) due to early depletion of ovarian follicles leads to primary amenorrhea or premature menopause. The causes can be genetic or secondary to infection, metabolic disease, autoimmune disorders, radiation, chemotherapy or physical damage to the ovary. Here in this paper we discuss the genetic causes of POI. The causes could be chromosomal disorders such as Turner syndrome (45, X) or structural X chromosomal abnormalities such as deletions/duplications/ring chromosome/X:autosome translocations. The causes could be single gene disorders with various inheritance patterns being possible such as autosomal dominant, autosomal recessive, X-linked dominant or X linked recessive We describe a panel of 157 genes which can be analysed on next generation sequencing panel and FMR1 gene which can be analysed on triple primer polymerase chain reaction method. [ABSTRACT FROM AUTHOR]

Background In cases of ovarian failure due to malnutrition, stem cell therapy is ineffective due to the lack of viability and differentiation of transplanted cells, resulting in low adaptation and survival rates. This study aimed to investigate whether stem cells cultured under low oxygen (O2) tension improve the adaptability and viability of cells in rats with ovarian failure. Methods After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C− groups, respectively. Results The slight increase gradually in cells expressing HSP70, VEGF-1, and GDF-9 was reported in C+, T2, T1, and C− groups, respectively. Caspase-3 expression was reported to decrease gradually in C+, T2, T1, and C− groups. Meanwhile, Graafian follicle count was reported to increase gradually in C+, T2, T1, and C− groups, respectively. Conclusions Based on those parameters, MSCs cultured under low O2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure.

Introduction. In the last decade, a high-throughput 16S ribosomal RNA (rRNA) sequencing allowed to markedly extend insights into female reproductive tract microbiome. However, evidence about its role on in vitro fertilization (IVF) outcomes remains scarce and controversial.Aim: to analyze literature data for assessing an impact of the vaginal, uterine, and ovarian microbiome on IVF outcomes.Materials and Methods. The review was carried out based on publications from available in PubMed/MEDLINE, EBSCO, ResearchGate, Google Academy and еLibrary databases released over the last 20 years. For this, there was search for keywords and their combinations in Russian- and English-written publications: «vaginal microbiome», «cervical microbiome», «uterine microbiome», «ovarian microbiome», «microbiome of ovarian follicles», «IVF», «miscarriage», «early pregnancy loss», «implantation failure», «ovarian failure», «inflammasome». Only full-text original articles and reviews published in peer-reviewed journals were included in the review. Exclusion criteria were as follows: studies containing less than 10 observations per group, abstracts of conferences, studies on the male reproductive tract microbiome. Duplicate publicationswere excluded. The publications were selected independently by two co-authors, and in case of discrepancy two other co-authors were involved.Results. Vaginal, uterine, and ovarian microbiomes were characterized by providing relevant classifications and the features related to implantation failures and pregnancy loss after IVF. It was found that a decline in total Lactobacillus level and elevated proportion of L. jensenii, G. vaginalis, and Proteobacteria in the vaginal microbiome were predictors of implantation failure. In addition, IVF failure was also associated with the presence of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Streptococcus, Haemophilus, Staphylococcus, Brevundimonas, and Ralstonia in the uterine cavity as well as Bifidobacterium, Gardnerella, and Klebsiella in the endometrial tissue. On the other hand, Lactobacillus dominance in the uterine microbiome has a favorable effect. The colonization of the follicle by any microorganisms as well as the presence of follicular fluid anaerobic bacteria-derived metabolite trimethylamine-N-oxide (TMAO) associated with bacterial vaginosis additionally alters IVF outcomes. Moreover, the role of infectious cues in lowered ovarian reserve has also been established. Activation of the NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome by microbe-derived ligands stimulates production of pro-inflammatory cytokines and contributes to reduced follicle number. Blocking NLRP3 in mouse experiments can delay depletion of the follicle pool and result in elevated fertility.Conclusion. Favorable IVF outcomes are associated with Lactobacillus predominance in the vaginal and endometrial microbiome as well as lack of follicular fluid microorganisms. TMAO detected in the follicular fluid as well as activated NLRP3 inflammasome serve as negative predictors of IVF outcomes.

Background Stem cell therapy shows applications potential for malnutrition-induced ovarian failure in rat models. However, it is ineffective because of the lack of viability and differentiation of transplanted stem cells, resulting in low adaptation and survival rates. We aimed to determine whether stem cells cultured under low oxygen (O 2) tension improves the adaptability and viability of stem cells, as well as ovarian failure. Methods After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O 2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C− groups, respectively. Results The slight increase gradually in cells expressing HSP70 (C+, T2, T1, and C− groups were 0.5 a±0.53, 1.7 a±0.82, 6.2 b±1.5, and 9.6 c±1.3, respectively), decrease gradually in cells expressing caspase-3 as an apoptosis indicator (C+, T2, T1, and C− groups were 0.2 a±0.42, 0.6 a±0.52, 4.8 b±1.03, and 7.3 c±1.42, respectively), and increase gradually in cells expressing VEGF-1 (C+, T2, T1, and C− groups were 10.8 c±1.55, 8.7 b±0.48, 0.4 a±0.52, and 0.2 a±0.42, respectively) and GDF-9 (C+, T2, T1, and C− groups were 5.8 c±1.47, 4.6 b±0.97, 0.5 a±0.53, and 0.3 a±0.48, respectively) were used as markers for viability and differentiation in ovarian tissue, indicating that MSCs cultured under low O 2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure. Furthermore, infertile female rats treated with MSCs cultivated under low O 2 tension had an enhanced ovarian tissue shape, as indicated by the increasing Graafian follicle count gradually (C+, T2, T1, and C− groups were 8.9 c±0.74, 4.5 b±0.71, 0.5 a±0.53, and 0.4 a±0.52, respectively). Conclusions MSCs cultured under low O 2 tension are an effective treatment for malnourished rats with ovarian failure.

Infertility is generally defined as the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. premature ovarian failure (POF) is a cause of female infertility, being estimated to affect 1% of the general population. This condition represents a loss of hormonal and germinative activity of the ovaries due to a lack in the number of active follicles in women under 40 years old. Regenerative medicine represents a complex therapeutic option and it consists of technologies such as the use of stem cells, tissue engineering, and gene therapy alone or in different combinations. Although the boundaries of regenerative medicine are not clearly outlined at present, this paper is aiming to review its possibility of treatment in the future in what concerns POF, focusing more on the use of stem cell therapy. Stem cell therapy could be a feasible therapeutic approach for POF as the cells can be easily obtained. However, additional clinical studies are needed because until now the majority of the literature focuses on animal models for the evaluation of the role of stem cells on treating POF. Additionally, the platelet-rich plasma (PRP) approach for POF should be kept in mind as it was shown to be useful in the regeneration of multiple types of tissue.

The tRNA methyltransferase 10 homologue A (TRMT10A) gene encodes tRNA methyl transferase, and biallelic loss of function mutations cause a recessive syndrome of intellectual disability, microcephaly, short stature and diabetes. A case with intellectual disability and distinctive features including microcephaly was admitted. She was diagnosed with epilepsy at 2.5 years old. At 3.6 years of age, severe short stature related to growth hormone (GH) deficiency was detected. She had an incidental diagnosis of diabetes at age 11.4 years which was negative for diabetes antibodies with persistent C-peptide level and she was treated with metformin. Spontaneous puberty did not begin until 15.7 years of age and she was found to have primary ovarian failure. A homozygous p.Arg127* mutation in TRMT10A was detected. In addition to the typical clinical features which characterize TRMT10A syndrome, we observed an unusual form of impaired glucose metabolism which presented in early childhood with hypoglycemia followed by diabetes in late childhood. GH deficiency and primary ovarian failure may also be additional findings of this syndrome. Patients with slow onset diabetes who are negative for autoantibodies and have extra-pancreatic features should be tested for all known subtypes of monogenic diabetes.

Introduction: Classical Hodgkin Lymphoma (HL) is a lymphoproliferative disease typically diagnosed in the young. The excellent results obtained with current treatment lead to long survival with age-related complications affecting patients' survival and quality of life. One issue affecting HL patients is infertility. This problem can be easily overcome in males with seminal liquid cryopreservation, however, in females it is more complex either in terms of the quality of the cryopreserved material or the patients' age at diagnosis. Moreover, not all chemo-or radio-therapies have the same negative impact on fertility. The main objectives of this study was to collect epidemiological information on HL patients involved in fertility preservation counseling and to analyze the impact of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the standard treatment for HL, on ovarian function, hormonal levels and ovarian and uterine tissue morphologies. Patterns of fertility preservation were also reported. Methods: Data were obtained from 270 female patients at HL onset who were interested in fertility counseling prior to therapy initiation. Each patient was assessed at HL diagnosis for levels of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), and 17β-oestradiol (17β-oe), with additional assessments at 6 and 12 months after chemotherapy. Patients were evaluated with ultrasound scans to study the number of ovarian follicles and the degree of uterine thickness at the same timepoints. Results: The average patient AMH level showed a statistically significant reduction at 6 months after chemotherapy (p=0.05) and by the 12 month time point returned to near pre-chemotherapy values. FSH and 17β-oe levels did not significantly vary throughout the study period. ABVD chemotherapy was associated with a significant reduction of both ovarian follicles and endometrial thickness at the 6 month time point followed by a recovery at the 12 time point in both ovaries. Different results were observed when patients changed treatment to a more intensive one. Discussion: Based on the results from the hormonal measurements and the follicle echography, it appears that the toxic effect of ABVD on fertility is transient, whereas, in contrast, more intensive therapies may potentially be more harmful and long-lasting. [ABSTRACT FROM AUTHOR]

IntroductionClassical Hodgkin Lymphoma (HL) is a lymphoproliferative disease typically diagnosed in the young. The excellent results obtained with current treatment lead to long survival with age-related complications affecting patients’ survival and quality of life. One issue affecting HL patients is infertility. This problem can be easily overcome in males with seminal liquid cryopreservation, however, in females it is more complex either in terms of the quality of the cryopreserved material or the patients’ age at diagnosis. Moreover, not all chemo- or radio-therapies have the same negative impact on fertility.The main objectives of this study was to collect epidemiological information on HL patients involved in fertility preservation counseling and to analyze the impact of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the standard treatment for HL, on ovarian function, hormonal levels and ovarian and uterine tissue morphologies. Patterns of fertility preservation were also reported.MethodsData were obtained from 270 female patients at HL onset who were interested in fertility counseling prior to therapy initiation. Each patient was assessed at HL diagnosis for levels of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), and 17β-oestradiol (17β-oe), with additional assessments at 6 and 12 months after chemotherapy. Patients were evaluated with ultrasound scans to study the number of ovarian follicles and the degree of uterine thickness at the same timepoints.ResultsThe average patient AMH level showed a statistically significant reduction at 6 months after chemotherapy (p=0.05) and by the 12 month time point returned to near pre-chemotherapy values. FSH and 17β-oe levels did not significantly vary throughout the study period. ABVD chemotherapy was associated with a significant reduction of both ovarian follicles and endometrial thickness at the 6 month time point followed by a recovery at the 12 time point in both ovaries. Different results were observed when patients changed treatment to a more intensive one.DiscussionBased on the results from the hormonal measurements and the follicle echography, it appears that the toxic effect of ABVD on fertility is transient, whereas, in contrast, more intensive therapies may potentially be more harmful and long-lasting.

The tRNA methyltransferase 10 homologue A (TRMT10A) gene encodes tRNA methyl transferase, and biallelic loss of function mutations cause a recessive syndrome of intellectual disability, microcephaly, short stature and diabetes. A case with intellectual disability and distinctive features including microcephaly was admitted. She was diagnosed with epilepsy at 2.5 years old. At 3.6 years of age, severe short stature related to growth hormone (GH) deficiency was detected. She had an incidental diagnosis of diabetes at age 11.4 years which was negative for diabetes antibodies with persistent C-peptide level and she was treated with metformin. Spontaneous puberty did not begin until 15.7 years of age and she was found to have primary ovarian failure. A homozygous p.Arg127* mutation in TRMT10A was detected. In addition to the typical clinical features which characterize TRMT10A syndrome, we observed an unusual form of impaired glucose metabolism which presented in early childhood with hypoglycemia followed by diabetes in late childhood. GH deficiency and primary ovarian failure may also be additional findings of this syndrome. Patients with slow onset diabetes who are negative for autoantibodies and have extra-pancreatic features should be tested for all known subtypes of monogenic diabetes. [ABSTRACT FROM AUTHOR]

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To evaluate the serum level of prolidase, which is a marker of fibrogenic activity, in women with idiopathic primary ovarian insufficiency (POI). This is a prospective case-control study. Serum prolidase level was compared between the study group including 68 women with POI and control group including 65 normally menstruating women. Serum proline and hydroxyproline levels were also compared. Correlation analyses were performed between the prolidase level and POI related parameters including estradiol (E), follicle stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, and presence of POI family history. Serum prolidase and proline level were significantly increased in women with the diagnosis of POI compared to the control group (1082.57 (147.53) vs 981.13 (223.26) U/L, 233.30 (83.16) vs 218.94 (82.59) µmol/L, respectively). Prolidase level found to have significant correlations with AMH, E, FSH levels, and presence of POI family history (r = −0.49, p = 0.001; r = −0.39, p = 0.001; r = 0.42, p = 0.001; r = 0.22, p = 0.01; respectively). In receiver operating characteristics analysis, prolidase was shown to be a discriminative factor for POI at 1031.14 U/L cut-off value with 75 % sensitivity and 65 % specificity. The area under curve was 0.71 [(95 % CI: 0.62–0.79), p = 0.001]. The current study revealed increased prolidase level in women with POI. Serum prolidase level was also negatively correlated with the serum AMH level. Considering the present findings, prolidase may be a candidate molecule in assessment of POI cases. [ABSTRACT FROM AUTHOR]

To determine the familiality of primary ovarian insufficiency (POI) at population level through examination of multigenerational genealogical information linked to electronic medical records. Case-control study. Not applicable. Women with POI were identified using International Classification of Disease 9 and 10 codes in electronic medical records (1995–2021) from 2 major health care systems in Utah and reviewed for accuracy. Cases were linked to genealogy information in the Utah Population Database (UPDB). All included POI cases (n = 396) were required to have genealogy information available for at least 3 generations of ancestors. The risk of POI in relatives was compared with population rates for POI matched by age, sex, and birthplace. Not applicable. Relative risk of POI in first-, second-, and third-degree relatives. We identified 396 validated cases of POI with an associated 2,132 first-degree relatives, 5,245 second-degree relatives, and 10,853 third-degree relatives. We found an increased risk of POI among the extended relatives of cases. Specifically, first-degree relatives demonstrated an 18-fold increased risk of POI compared with controls relative risk ([RR],18.52 95% confidence interval [CI], 10.12–31.07), second-degree relatives demonstrated a 4-fold increase (RR, 4.21; CI, 1.15–10.79), and third-degree relatives demonstrated a 2.7-fold increase (RR, 2.65; CI, 1.14–5.21]). This is the first population-based study to assess the familial clustering of POI. The data demonstrate excess familiality, familial clustering of POI in excess compared with matched population rates of disease, among first-, second-, and third-degree relatives. These findings support a genetic contribution to POI. [ABSTRACT FROM AUTHOR]

Infertility is generally defined as the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. premature ovarian failure (POF) is a cause of female infertility, being estimated to affect 1% of the general population. This condition represents a loss of hormonal and germinative activity of the ovaries due to a lack in the number of active follicles in women under 40 years old. Regenerative medicine represents a complex therapeutic option and it consists of technologies such as the use of stem cells, tissue engineering, and gene therapy alone or in different combinations. Although the boundaries of regenerative medicine are not clearly outlined at present, this paper is aiming to review its possibility of treatment in the future in what concerns POF, focusing more on the use of stem cell therapy. Stem cell therapy could be a feasible therapeutic approach for POF as the cells can be easily obtained. However, additional clinical studies are needed because until now the majority of the literature focuses on animal models for the evaluation of the role of stem cells on treating POF. Additionally, the platelet-rich plasma (PRP) approach for POF should be kept in mind as it was shown to be useful in the regeneration of multiple types of tissue. [ABSTRACT FROM AUTHOR]

Impaired reproductive health is a worldwide problem that affects the psychological well-being of a society. Despite the technological developments to treat infertility, the global infertility rate is increasing significantly. Many infertility conditions are currently treated using various advanced clinical approaches such as intrauterine semination (IUI), in vitro fertilization (IVF), and intracytoplasmic injection (ICSI). Nonetheless, clinical management of some conditions such as dysfunctional endometrium, premature ovarian failure, and ovarian physiological aging still pose significant challenges. Stem cells based therapeutic strategies have a long-standing history to treat many infertility conditions, but ethical restrictions do not allow the broad-scale utilization of adult mesenchymal stromal/stem cells (MSCs). Easily accessible, placental derived or amniotic stem cells present an invaluable alternative source of non-immunogenic and non-tumorigenic stem cells that possess multilineage potential. Given these characteristics, placental or amniotic stem cells (ASCs) have been investigated for therapeutic purposes to address infertility in the last decade. This study aims to summarize the current standing and progress of human amniotic epithelial stem cells (hAECs), amniotic mesenchymal stem cells (hAMSCs), and amniotic fluid stem cells (hAFSCs) in the field of reproductive medicine. The therapeutic potential of these cells to restore or enhance normal ovarian function and pregnancy outcomes are highlighted in this study. [ABSTRACT FROM AUTHOR]

Background: Stem cell therapy shows applications potential for malnutrition-induced ovarian failure in rat models. However, it is ineffective because of the lack of viability and differentiation of transplanted stem cells, resulting in low adaptation and survival rates. We aimed to determine whether stem cells cultured under low oxygen (O 2) tension improves the adaptability and viability of stem cells, as well as ovarian failure. Methods: After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O 2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C− groups, respectively. Results: The slight increase in cells expressing HSP70 (C+, T2, T1, and C− groups were 0.5 a±0.53, 1.7 a±0.82, 6.2 b±1.5, and 9.6 c±1.3, respectively), decrease in cells expressing caspase-3 as an apoptotic inhibitor (C+, T2, T1, and C− groups were 0.2 a±0.42, 0.6 a±0.52, 4.8 b±1.03, and 7.3 c±1.42, respectively), and increase in cells expressing VEGF-1 (C+, T2, T1, and C− groups were 10.8 c±1.55, 8.7 b±0.48, 0.4 a±0.52, and 0.2 a±0.42, respectively) and GDF-9 (C+, T2, T1, and C− groups were 5.8 c±1.47, 4.6 b±0.97, 0.5 a±0.53, and 0.3 a±0.48, respectively) were used as markers for viability and differentiation in ovarian tissue, indicating that MSCs cultured under low O 2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure. Furthermore, infertile female rats treated with MSCs cultivated under low O 2 tension had an enhanced ovarian tissue shape, as indicated by the increasing Graafian follicle count (C+, T2, T1, and C− groups were 8.9 c±0.74, 4.5 b±0.71, 0.5 a±0.53, and 0.4 a±0.52, respectively). Conclusions: MSCs cultured under low O 2 tension are an effective treatment for malnourished rats with ovarian failure.

Abstract Background Missense mutations in the mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene are clinically associated with infantile mitochondrial cardiomyopathy or adult-onset leukoencephalopathy with early ovarian failure. To date, approximately 40 cases have been reported related to AARS2 mutations, while its genetic and phenotypic spectrum remains to be defined. Case presentation We identified a 24-year-old Chinese female patient with adult-onset leukoencephalopathy carrying novel compound heterozygous pathogenic mutations in the AARS2 gene (c.718C > T and c.1040 + 1G > A) using a whole-exome sequencing approach. Conclusions Our findings further extend the mutational spectrum of AARS2-related leukoencephalopathy and highlight the importance of the whole-exome sequencing in precisely diagnosing adult-onset leukoencephalopathies.

Coats plus syndrome is an autosomal recessive multisystemic and pleiotropic disorder affecting the eyes, brain, bone, and gastrointestinal tract, usually caused by compound heterozygous variants of the conserved telomere maintenance component 1 gene (CTC1), involved in telomere homeostasis and replication. So far, most reported patients are compound heterozygous for a truncating mutation and a missense variant. The phenotype is believed to result from telomere dysfunction, with accumulation of DNA damage, cellular senescence, and stem cell depletion. Here, we report a 23-year-old female with prenatal and postnatal growth retardation, microcephaly, osteopenia, recurrent fractures, intracranial calcification, leukodystrophy, parenchymal brain cysts, bicuspid aortic valve, and primary ovarian failure. She carries a previously reported maternally inherited pathogenic variant in exon 5 (c.724_727del, p.(Lys242Leufs*41)) and a novel, paternally inherited splice site variant (c.1617+5G>T; p.(Lys480Asnfs*17)) in intron 9. CTC1 transcript analysis showed that the latter resulted in skipping of exon 9. A trace of transcripts was normally spliced resulting in the presence of a low level of wild-type CTC1 transcripts. We speculate that ovarian failure is caused by telomere shortening or chromosome cohesion failure in oocytes and granulosa cells, with early decrease in follicular reserve. This is the first patient carrying 2 truncating CTC1 variants and the first presenting primary ovarian failure. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is the imbalance between intake and nutritional needs, resulting in a decrease in body weight, composition, and physical function. Malnutrition causes infertility due to intestinal and liver degeneration,which may progress to testicular and ovarian degeneration. Methods: An infertile female rat model with a degenerative ovary was induced with malnutrition through a 5-day food fasting but still had drinking water. The administration of (T1) 30% (v/v) and (T2) 50% (v/v) forest honey ( Apis dorsata) were performed for ten consecutive days, whereas the (T+) group was fasted and not administered forest honey and the (T−) group has not fasted and not administered forest honey. Superoxide dismutase, malondialdehyde, IL-13 and TNF-α cytokine expressions, and ovarian tissue regeneration were analyzed. Results: Superoxide dismutase was significantly different ( ppppp Conclusion: The 10-day administration of 50% (v/v) forest honey can be an effective therapy for ovarian failure that caused malnutrition in the female rat model.

Objective: To assess the impacts of Platelet-Rich Plasma(PRP) and Granulocyte Colony-Stimulating Factor(G-CSF) on a rat model with induced ovarian follicular damage caused by cyclophosphamide(Cy)., Materials and Methods: Forty-two Sprague-Dawley rats were randomly allocated into seven distinct groups as; Group 1(control): NaCl intraperitoneal (IP) injection was administered on days D1, D7, and D14. Group 2(Cy): Cy IP injection on D1 + NaCl IP injection on D7 and D14 were administered. Group 3(PRP): PRP IP injection on D1,D7 and D14 were administered. Group 4(Cy + PRP): Cy IP injection on D1 and PRP IP injection on D1, D7 and D14 were administered. Group 5(G-CSF): G-CSF IP injection on D1, D7 and D14 were administered. Group 6(Cy + G-CSF): Cy IP injection on D1+ G-CSF IP injection on D1, D7 and D14 were administered. Group 7(Cy + PRP + G-CSF): Cy IP injection on D1+ PRP IP injection on D1,D7 and D14+ G-CSF IP injection on D1,D7 and D14 were administered. Follicular number, histological scores of AMH and INSL3 stained follicles at different stages of follicular development, and serum Anti-Müllerian hormone(AMH) were evaluated., Results: The primary, secondary, and antral follicle intensity scores for AMH-positive staining were most prominent in Groups 3 and 5. There was no significant difference between groups 4, 6 and 7 compared to group 1 in terms of follicule counts and AMH staining. The intensity scores of AMH-positive staining follicles were notably reduced in group 2 compared to groups 4, 6, and 7, with a significant difference ( p  < .01). Among the groups, group 2 exhibited the least intense antral follicle staining for INSL3, displaying a significant difference( p  < .01) compared to the remaining groups., Conclusions: Autologous PRP and G-CSF might protect ovarian function in the face of ovarian damage caused by Cy-induced effects.

Perrault syndrome (PRLTS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss in both sexes and ovarian dysfunction in females with a 46, XX karyotype. Due to its rarity and diagnostic challenges, herein we report on a 26-year-old woman who presented with secondary amenorrhea, congenital deafness in one ear, and progressive hearing loss in the other. Physical examination showed poorly developed breasts and normal external genitalia. Lab tests revealed high follicle-stimulating hormone (FSH) levels, indicating ovarian failure. Imaging revealed a small uterus and streak ovaries without follicular activity. Initially misdiagnosed with various overlapping syndromes such as Turner, Turner mosaic, and Swyer syndromes, she was started on oral contraceptive pills which induced menstruation and minimal breast development but caused mood swings and depression, leading to inconsistent use. Later, karyotyping revealed a normal 46,XX karyotype, shrouding the case in mystery. A few years later, after additional investigations, her hearing loss and reproductive disruptions were connected, and she was diagnosed with PRLTS. The absence of neurological symptoms suggests type I PRLTS. This case underscores the diagnostic challenges of PRLTS and highlights the importance of genetic testing for accurate diagnosis. It also emphasizes the need for a multidisciplinary approach and further research to improve understanding and management of this rare condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iqbal et al.)

Objective: There are diverse findings concerning the use of platelet-rich plasma (PRP) in assisted reproduction treatment (ART) cycles of infertile women with low ovarian reserve, ovarian failure or implantation failure due to endometrial problems. A debate continues regarding the benefit of this technique because of the low number of evidence-based studies. Mechanism: Different PRP preparation methods have been described in the literature, aiming to obtain the highest number of platelets following centrifugation steps. Findings in brief: Research on the use of PRP in female infertility aims to improve the deteriorated hormonal profile, gamete production and implantation of the embryo into the endometrium. Conclusions: This paper reviewed literature evaluating the impact of PRP on the outcomes of subsequent ART cycles in infertile women. PRP is a safe and easy-to-apply procedure and can be used as an ’add-on’ therapy in patients with reduced ovarian reserve, ovarian failure or implantation failure prior to the in vitro fertilization (IVF) cycle, although it is still regarded as an empirical treatment method. Further studies should be conducted to enlighten the subject.

Background: Malnutrition is the imbalance between intake and nutritional needs, resulting in a decrease in body weight, composition, and physical function. Malnutrition causes infertility due to intestinal and liver degeneration,which may progress to testicular and ovarian degeneration. Methods: An infertile female rat model with a degenerative ovary was induced with malnutrition through a 5-day food fasting but still had drinking water. The administration of (T1) 30% (v/v) and (T2) 50% (v/v) forest honey (Apis dorsata) were performed for ten consecutive days, whereas the (T+) group was fasted and not administered forest honey and the (T−) group has not fasted and not administered forest honey. Superoxide dismutase, malondialdehyde, IL-13 and TNF-α cytokine expressions, and ovarian tissue regeneration were analyzed. Results: Superoxide dismutase was significantly different (p

OBJECTIVE: In recent years, the incidence of premature ovarian failure has been on the rise, showing the young trend. Because of the complex etiology of premature ovarian failure and poor clinical outcome, there is an urgent need to find a safe and effective treatment modality. This study systemically assessed the effectivity of stem cell transplantation of premature ovarian failure animal models. METHODS: PubMed, The Cochrane Library, EMbase, CBM, CNKI, Wanfang, and VIP were retrieved before June 10, 2020. A series of studies on the treatment of premature ovarian failure animal models by stem cells were collected. Two evaluators independently screened the literature and extracted the data. The SYRCLE risk of bias assessment scale for animal experiments was used to evaluate the quality of the literature. The primary outcome indicators were analyzed using RevMan 5.3 software for meta-analysis. RESULTS: (1) A total of 13 randomized controlled animal experimental studies were included, with 348 mice, and overall quality was moderate. Stem cell group (n=184) only received stem cell transplantation, and control group (n=164) only received blank control, normal saline or PBS intervention. (2) Meta-analysis results showed that compared with the control group, serum estrogen level (SMD=3.02, 95%CI: 1.87-4.18, P < 0.000 01), serum anti-Müllerian hormone level (ng/mL subgroup: SMD=4.77, 95%CI: 0.95-8.59, P=0.01; pg/mL subgroup: SMD=4.94, 95%CI: 0.91-8.97, P=0.02), serum luteinizing hormone level (SMD=- 1.47, 95%CI: -1.73 to -1.22, P < 0.000 01), the number of follicles at all levels (SMD=1.91, 95%CI: 0.85-2.97, P=0.000 4) and fertility rate increased (RR=2.07, 95%CI: 1.39-3.09, P=0.000 4), but serum follicle-stimulating hormone level decreased (P < 0.000 1) in the stem cell group. The number of follicles at all levels was significantly higher in the stem cell group than that in the control group (P < 0.05). Subgroup analysis showed that with the increase of follow-up time, the number of primordial follicles, primary follicles and secondary follicles was significantly increased (P < 0.05), and the number of atresic follicles was significantly decreased (P < 0.05). Different types of stem cell transplantation could improve the serum estrogen level, and the recovery of serum estrogen level was more significant with the increase of unit dose of stem cell injection (P < 0.05). CONCLUSION: Available evidence from animal studies suggests that stem cell transplantation is effective in treating premature ovarian failure model mice. Stem cell transplantation induces an increase in estrogen levels, a decrease in follicle-stimulating hormone levels, and an improvement in follicle numbers at all levels in premature ovarian failure. Stem cells have some restorative effects on the ovary, but large samples and high quality human trials are still needed to verify clinical application effects. [ABSTRACT FROM AUTHOR]

Background: Vanishing white matter (VWM) is one of the most prevalent leukoencephalopathies and is caused by recessive mutations in gene eIF2B1-5. The onset may vary from an antenatal disorder that is rapidly fatal to an adult-onset disorder with chronic progressive deterioration.Methods: Based on a comprehensive study of 14 juvenile/adult patients diagnosed in our department as well as a review of 71 previously reported cases of genetically confirmed juvenile/adult-onset VWM since 2001, we attempted to delineate the clinical symptoms, disease evolution, episodic aggravation, associated symptoms, MRI findings and genotypic characteristics of adult VWM.Results: The onset age of neuropsychiatric symptoms was 23.4 ± 10.6 years, and the mean follow-up time was 8.1 ± 4.8 years. Major clinical symptoms included headache, epilepsy, cognitive decline, cerebellar ataxia, and urinary disturbances. Episodic aggravation was found in 42.9% of the patients in our series. Molecular studies revealed fourteen novel missense mutations. Diffuse abnormal signals characterized by T1-weighted hypointensity and T2-weighted hyperintensity were observed in the supratentorial white matter.Conclusions: The symmetrical leukoencephalopathy must be considered in patients of any age with premature ovarian failure or optic neuropathy. The VWM disease spectrum consists of characteristic imaging findings in combination with extremely wide variability in VWM patients. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic Ovarian Syndrome (PCOS) is known to be an endocrine state that is characterized by oligomenorrhea, hyperandrogenism, and highly cystic follicles in the ovaries. The use of food ingredients and traditional medicine in Asian countries is well known, and previous studies have shown that Ecklonia cava K. [Alariaceae] (EC) is able to alleviate PCOS symptoms. D-Chiro-inositol (DCI) administration in pathologies where steroid biosynthesis is a crucial factor, i.e., PCOS, has provided satisfactory results. Methods: Therefore, we studied the synergistic effects of the two previously known active compounds. In rats with letrozole-induced PCOS, we focused on alternative therapies using EC and/or DCI extracts to alleviate ovarian failure. Results: As a nonsteroidal aromatase inhibitor, letrozole inhibits the conversion of testosterone to estrogen and subsequently causes PCOS. We divided 6-week-old female mice into the following six groups and evaluated them: vehicle, PCOS, PCOS + MET (metformin), PCOS + DCI, PCOS + EC, and PCOS + DCI + EC. In our study, PCOS rats treatedwith EC and DCI had lowserumLH and T levels and lowserumlevels of inflammatory cytokines such as TNFa and IL-6. These treatments also appeared to regulate the production of factors that affect follicle formation and inflammation in the ovaries. Conclusion: We concluded that EC extract and/or DCI administration influenced aromatase production and reduced LH and T stimulation, and cotreatment with EC and DCI consequently restored ovarian dysfunction or anti-inflammatory responses in rats with PCOS-like symptoms. [ABSTRACT FROM AUTHOR]

Aim: To develop a predictive model for ovarian failure (OF) after chemotherapy in young post-pubertal women with cancer. Methods: Retrospective, monocentric cohort study including 348 patients referring to the Oncofertility Unit of San Raffaele Hospital (Milan, Italy) from August 2011 to January 2020. A predictive model was constructed by multivariate logistic regression and receiver operating characteristic analysis. Results: Data about menstrual function resumption were available for 184 patients. The best predictive model for OF was identified by the combination of age; number of chemotherapy lines; vincristine, adriamycin, ifosphamide/adriamycin, ifosphamide; capecitabine; adriamycin, bleomycine, vinblastine, doxorubicin (area under the curve = 0.906; CI 95% 0.858-0.954; p = 0.0001). Conclusions: The model predicts the probability of loss of ovarian function at cancer diagnosis and with every change of treatment. [ABSTRACT FROM AUTHOR]

Backgroud: Amenorrhea and ovarian disorders are a common concern of women under the age of 40, a condition medically known as premature ovarian failure (POF). The incidence of POF among Egyptian women before the age of 40, is about 8% that exceeds the global incidence which is about 1%. Chemotherapeutic agents were linked to toxicity of ovarian tissues and disturbance of ovarian functions. Provision of a suitable protective agent with high efficacy, low side effects and cost is a major challenge in the field of oncofertility. Aim of the Study: Is to evaluate the mechanism of PRP treatment in induced ovarian failure due to cyclophosphamide. Materials and Methods: The present study was carried out on twenty-nine albino rats. Twenty-four adult female albino rats were used as the experimental group. Five age-matched healthy male albino rats were used to get the PRP. The twenty-four adult female albino rats were randomly assigned into three groups (control, group II: received cyclophosphamide, group III: received cyclophosphamide and PRP). Plasma estradiol and progesterone levels were measured on day 22 after cyclophosphamide treatment before experimental rats euthanasia. The rats were euthanized and ovaries were anatomically examined using dissecting stereomicroscope. Sections of the ovaries were prepared and examined histologically, immunohistochemicaly and using transmission electron microscope. Results: Cyclophosphamide treated groups showed signs of degeneration of follicles and oocyte and deterioration of ovarian functions. PRP treated group showed improved appearance of ovarian follicles and improved ovarian functions. Conclusion: PRP seems to have protective effects on ovarian tissues and functions and its concomitant use with cyclophosphamide helps to restore the ovarian tissues. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine if interindividual genetic variation in single-nucleotide polymorphisms (SNPs) related to age at natural menopause is associated with risk of ovarian failure in breast cancer survivors.MethodsA prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 SNPs previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, and also the risk variable, and time to ovarian failure (>12 months of amenorrhea) was tested using time-to-event methods.ResultsMedian age at enrollment was 40.5 years (range 20.6-46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable was significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure, and lower body mass index were related to shorter time to ovarian failure.ConclusionsThirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors.

Background: Malnutrition is a crucial issue that contributes to approximately 45% of deaths among children under 5 years old and even >50% of deaths when accompanied by diarrhea. Several studies have stated that the use of honey can overcome cases of infertility due to malnutrition. Methods: An infertile female rat model with a degenerative ovary was induced with malnutrition through a 5-day food fasting but still had drinking water. The administration of (T1) 30% (v/v) and (T2) 50% (v/v) forest honey ( Apis dorsata) were performed for ten consecutive days, whereas the (T+) group was fasted and not administered forest honey and the (T−) group has not fasted and not administered forest honey. Superoxide dismutase, malondialdehyde, IL-13 and TNF-α cytokine expressions, and ovarian tissue regeneration were analyzed. Results: Antioxidant activity (SOD) was significantly different ( ppppp Conclusion: The 10-day administration of 50% (v/v) forest honey can be an effective therapy for ovarian failure that caused malnutrition in the female rat model.

Abstract Background Several studies have shown that coenzyme Q10 (CoQ10) can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility due to ovarian aging. However, few studies have examined the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs and recovers ovarian function in a 4-vinylcyclohexene diepoxide (VCD)-induced mouse model of ovarian failure. Methods Forty female C57BL/6 mice aged 6 weeks were randomly divided into four groups (n = 10/group): a control group administered saline orally, a CoQ10 group administered 150 mg/kg/day of CoQ10 orally in 1 mL of saline daily for 14 days, a VCD group administered 160 mg/kg/day of VCD i.p. in 2.5 mL of saline/kg for 5 days, and a VCD + CoQ10 group administered VCD i.p. for 5 days injection and CoQ10 (150 mg/kg/day) orally for 14 days. After treatment, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure counts and the expressions of Oct-4 and MVH were also evaluated after culturing OSE for 3 weeks. In a second experiment, 32 female mice were administered CoQ10 as described above, induced to superovulate using PMSG and hCG, and mated. Numbers of zygotes and embryo development rate were examined. Results Postcultured OSE showed significant increases in the numbers of oocyte-like structure and that the expression of Oct-4 and MVH were higher in the VCD + CoQ10 group than in the VCD group (p

Leukoencephalopathy with vanishing white matter (LVWM) is an autosomal recessive disease. Ovarioleukodystrophy is defined as LVWM in females showing signs or symptoms of gradual ovarian failure. We present a 38-year-old female with ovarioleukodystrophy who showed status epilepticus, gait instability, slurred speech, abdominal tendon hyperreflexia, and ovarian failure. Abnormal EEG, characteristic magnetic resonance, and unreported EIF2B5 compound heterozygous mutations [c.1016G>A (p.R339Q) and c.1157G>A (p.G386D)] were found. Furthermore, the present report summarizes 20 female patients with adult-onset ovarioleukodystrophy and EIF2B5 gene mutations. In conclusion, a new genetic locus for LVWM was discovered. Compared with previous cases, mutations at different EIF2B5 sites might have different clinical manifestations and obvious clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Missense mutations in the mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene are clinically associated with infantile mitochondrial cardiomyopathy or adult-onset leukoencephalopathy with early ovarian failure. To date, approximately 40 cases have been reported related to AARS2 mutations, while its genetic and phenotypic spectrum remains to be defined.Case Presentation: We identified a 24-year-old Chinese female patient with adult-onset leukoencephalopathy carrying novel compound heterozygous pathogenic mutations in the AARS2 gene (c.718C > T and c.1040 + 1G > A) using a whole-exome sequencing approach.Conclusions: Our findings further extend the mutational spectrum of AARS2-related leukoencephalopathy and highlight the importance of the whole-exome sequencing in precisely diagnosing adult-onset leukoencephalopathies. [ABSTRACT FROM AUTHOR]

Background: Graft-versus-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD in the female genital tract can cause sinusorrhagia, dyspareunia, synechia, and even complete vagina occlusion.Purpose: This prospective study aimed to evaluate the clinical characteristics and effects of preventive and prompt treatment for genital GVHD in females undergoing HSCT (n = 40).Results: Genital GVHD was diagnosed in 11 of 40 patients (27.5%), and the most common complaint was vaginal dryness (54.6%). The majority of patients (63.6%) presented mild genital GVHD (clinical score 1), with interlabial fissures and lichen-like lesions, while a minority of patients (9.1%) presented advanced genital GVHD (clinical score 3) with the fusion of the small and large lips. The median time of onset of genital GVHD signs was 10 months after HSCT, concomitant with GVHD in the skin and oral cavity. Personalized and topical therapy was effective in most cases (81.8%), and no patient required surgical intervention.Conclusion: We confirmed that female genital GVHD affects approximately one-third of females undergoing HSCT, highlighting the importance of periodic gynecological monitoring for early detection and treatment to improve care for these females. [ABSTRACT FROM AUTHOR]