14,996 research outputs found

    Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency

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    PURPOSE: Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. METHODS: We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55–200 CGG repeats) and intermediate (45–54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881). RESULTS: The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7–17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8–5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02–5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency. CONCLUSION: FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause

    Chromosomal Abnormalities and Menstrual Cycle Disorders

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    Chromosomal abnormalities have long been recognized as a cause of menstrual cycle disorders, premature ovarian insufficiency, and recurrent pregnancy loss. In women with X chromosome abnormalities, premature ovarian insufficiency is mainly a consequence of ovarian follicle depletion, due to insufficient initial follicle number and/or spontaneous accelerated follicle loss. The level of X chromosome mosaicism and its reproductive significance is still under debate. In our study, we evaluated the contribution of X chromosome abnormalities in women with sporadic idiopathic premature ovarian insufficiency (POI) and in women with a history of recurrent pregnancy loss. The results show that X aneuploidy and low-level mosaicism have reproductive significance in the phenotypically normal women with recurrent pregnancy loss and/or fertility problems. These results have practical implications for genetic counseling and fertility treatment

    Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

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    Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

    Spontaneous pregnancy in a patient with premature ovarian insufficiency after a failed attempt of ovulation induction

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    Premature ovarian insufficiency (POI) is defined as intermittent or permanent gonadal insufficiency before age of 40 years. POI causes female infertility hence pregnancies are uncommon but not impossible. Ovarian failure is not permanent, unlike menopause. There could be intermittent ovulation and spontaneous pregnancy. Many protocols aimed to restore ovarian functions have been described in the recent years. This is a case of POI women who conceived spontaneously in the immediate menstrual cycle after a failed attempt at ovarian stimulation following many years on hormone replacement therapy (HRT). She had an unremarkable pregnancy and delivered a healthy baby via caesarean section

    Premature Ovarian Insufficiency

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    Premature ovarian insufficiency (POI) is a heterogeneous disorder, affecting approximately 1% of women before the age of 40. Heterogeneity of POI is reflected by various causes. The known causes are genetic defects, autoimmune ovarian damage, metabolic, iatrogenic following surgery, cancer therapy, and environmental factors. However, in most cases, the cause remains unknown (idiopathic POI). The main symptom is the absence of regular menstrual cycles, and the diagnosis is confirmed by the raised gonadotropins and low estradiol. The disorder usually leads to infertility and has long-term comorbidities such as cardiovascular diseases, osteoporosis, and cognitive impairments. Management includes the use of hormone replacement therapy till the age of natural menopause. In women having fertility issues, the spontaneous conception varies between 5 and 10%, and in vitro fertilization with donor oocytes remains the treatment of choice. Moreover, fertility preservation options can be offered to some patients with cancer and those at risk of early menopause, such as those with familial cases of POI. Further research is clearly needed, to identify new mechanisms which may improve the prediction of the early onset of the disease

    Premature ovarian insufficiency

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    Premature ovarian insufficiency (POI) is a clinical syndrome defined as the loss of ovarian activity before the age of 40. POI is a life-changing diagnosis, with profound physical and psychological consequences. Spontaneous POI affects approximately 1% of women under the age of 40. However, the rising incidence of iatrogenic POI is of increasing concern. POI is a heterogeneous, multifactorial disorder, and in the majority of cases the etiology is unknown. The diagnosis of POI is based on the presence of amenorrhea and of an elevated gonadotropin level. Hormone replacement therapy should be used at least until the average age of menopause to alleviate the symptoms of hypoestrogenism and to prevent severe long term consequences especially those of cardiovascular diseases and osteoporosis. The treatment of these women should be coordinated by a multidisciplinary team. Women with POI should be informed that there is a small chance of spontaneous pregnancy. IVF with donor oocytes represents the highest chance for pregnancy in these patients. Further research is needed to identify the population in risk in a timely manner and to find mechanisms that can prolong, recover, or preserve ovarian function

    Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

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    The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2 ng/mL (sensitivity 73.3 %, specificity 84 %) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26 % of women without gynecologic diseases, in 80 % of women with recent diagnosis of ovarian cancer and in 24 % women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73 % women with recurrent ovarian cancer and in 47 % women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also
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