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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of premature ovarian failure is based on the finding of amenorrhoea before age 40 associated with follicle-stimulating hormone levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work up. There is no role for ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the most successful being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue or oocyte cryopreservation and in vitro maturation of oocytes hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.
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PMID:Premature ovarian failure. 1749 81

Gonadal dysfunction and fertility problems are adverse effects of cancer treatment or may be associated with specific malignancies. This review focuses on these problems in the young cancer survivors, where methods of protecting or restoring endocrine function and fertility need to be considered. In females, treatment adverse effects can result in infertility, but premature ovarian failure (POF) is probably relevant for more female cancer survivors, affecting also those who do not wish post-treatment parenthood. POF affects present and future health, especially through oestrogen deficiency symptoms and an increased risk of developing osteoporosis. A lower risk of developing POF has been considered in young females than in older due to a larger pool of oocytes. However, a recent long-term follow-up study reported a prevalence of POF in young females with Hodgkin's lymphoma of 37% showing that young age at time of treatment only delays the development of POF. In male gonads, germ cells are much more sensitive to irradiation and chemotherapy than Leydig cells. Thus, infertility is a more common adverse effect than hypogonadism. Some malignancies are particular relevant. Persistent azoospermia was formerly common after treatment for Hodgkin's lymphoma, but currently, most patients recover spermatogenesis. Modern treatment of childhood acute lymphoblastic leukemia is also unlikely to cause infertility. Norwegian testicular cancer survivors diagnosed in 1980-1994 who attempted conception had an overall 15-year actuarial post-treatment paternity rate of 71% (range 48-92% depending on the treatment). However, the rate was significantly higher among men diagnosed in1989-1994 (over 80%) than in 1980-1988 (about 63%). Patients at risk for hypogonadism and infertility should be defined prior to treatment, and available methods for gonadal preservation should maximally be utilised. During follow-up, oncologists should routinely address these issues.
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PMID:Gonadal dysfunction and fertility problems in cancer survivors. 1749 15

In humans, the molecular mechanisms underlying ovarian follicle endowment and activation, which are closely related to the control of female reproduction, occurrence of menopause, and related diseases such as premature ovarian failure, are poorly understood. In the current study, we provide several lines of genetic evidence that the cyclin-dependent kinase (Cdk) inhibitor 1B (commonly known as p27(kip1) or p27) controls ovarian development in mice by suppressing follicle endowment and activation, and by promoting follicle death. In p27-deficient (p27(-/-)) mice, postnatal follicle assembly was accelerated, and the number of endowed follicles was doubled as compared with p27(+/+) mice. Moreover, in p27(-/-) ovaries the primordial follicle pool was prematurely activated once it was endowed, and at the same time the massive follicular death that occurs before sexual maturity was rescued by loss of p27. In early adulthood, however, the overactivated follicular pool in p27(-/-) ovaries was largely depleted, causing premature ovarian failure. Furthermore, we have extensively studied the molecular mechanisms underlying the above-mentioned phenotypes seen in p27(-/-) ovaries and have found that p27 controls follicular development by several distinct mechanisms at different stages of development of the ovary. For example, p27 controls oocyte growth by suppressing the functions of Cdk2/Cdc2-cyclin A/E1 in oocytes that are arrested at the diplotene stage of meiosis I. This function of p27 is distinct from its well-known role as a suppressor of cell cycle progression. In addition, we have found that p27 activates the caspase-9-caspase-3-caspase-7-poly (ADP-ribose) polymeraseapoptotic cascade by inhibiting Cdk2/Cdc2-cyclin A/B1 kinase activities in follicles, thereby inducing follicle atresia. Our results suggest that the p27 gene is important in determining mammalian ovarian development. This study therefore provides insight into ovary-borne genetic aberrations that cause defects in folliculogenesis and infertility in humans.
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PMID:p27kip1 (cyclin-dependent kinase inhibitor 1B) controls ovarian development by suppressing follicle endowment and activation and promoting follicle atresia in mice. 1756 40

Genes for reproduction are enriched on the sex chromosomes and they may be involved in the many forms of X- or Y-linked infertility. Here we review the X-linked disorders of ovulation and we show that despite the relatively frequent observation of X chromosome rearrangements in women with ovarian dysgenesis or ovarian failure, the search for X-linked genes has not yet been very fruitful: only two genes have been demonstrated definitively, BMP15 and FMR1. However, the size of the rearrangements and the characteristics of some of the genes suggest that many of the X-linked genes only rarely may be causative and more frequently they may represent risk factors for premature ovarian failure (POF) and will have to be identified by specific approaches. Moreover, recent data seem to suggest a structural and novel role for the X chromosome in some of the POF rearrangements, and also that X-linked POF is not always dependent from the presence of X-linked genes.
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PMID:X chromosome and ovarian failure. 1759 7

Breast cancer is the most frequent cancer in reproductive age women. Although well known causal link between estrogen and breast cancer, the impact of ovulation induction on the risk of breast cancer still remains to be clarified. One of the recently recognized long term adverse effects of adjuvant cytotoxic chemotherapy given for breast cancer is premature ovarian failure and infertility, both of which significantly compromise the quality of life of a cancer survivor. Thanks to significant developments in assisted reproductive technologies these patients may benefit from a wide range of fertility preservation options. The most established technique is embryo cryopreservation; oocyte cryopreservation can be considered in single women; both of which require at least 2 weeks of ovarian stimulation beginning with the onset of the patient's menstrual cycle. Novel ovarian stimulation protocols using tamoxifen and letrozole can be used to increase the margin of safety in estrogen sensitive breast tumors. When there is no time available for ovulation induction, ovarian tissue can be cryopreserved for future transplantation without delay in cancer therapy. The benefit of ovarian protection by gonadotropin-releasing hormone analogues is unproven and unlikely, and thus this treatment should not be recommended as the sole method of fertility preservation.
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PMID:Assisted reproduction and breast cancer. 1792 31

Premature ovarian failure occurs in approximately 1:1000 women before 30 years, 1:250 by 35 years and 1:100 by the age of 40. It is characterized by primary or secondary amenorrhea and cannot be considered as definitive because spontaneous conception may occur in 5 to 10% of cases. In 95% of cases, premature ovarian failure is sporadic. The known causes of premature ovarian failure include chromosomal defects, autoimmune diseases, exposure to radiation or chemotherapy, surgical procedures, and certain drugs. Frequently, however, the etiology is not clear and these cases are considered to be idiopathic. Premature ovarian failure is defined by gonadal failure and high serum follicle-stimulating hormone (FSH) levels. Clinical approach includes emotional support, hormonal therapy with estrogens and progesterone or progestogens, infertility treatment, and prevention of osteoporosis and potential cardiovascular risk.
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PMID:[Premature ovarian failure: present aspects]. 1793 58

Female fragile X premutation carriers are at approximately 10-fold increased risk of premature ovarian failure (follicle stimulating hormone >40 mIU/mL, amenorrhea, age <40). A milder degree of premature ovarian aging (diminished ovarian reserve, where follicle stimulating hormone levels are typically 10-20 mIU/mL) results in infertility. Approximately 10% of fertility clinic patients have this diagnosis. A cohort of 20 women diagnosed with diminished ovarian reserve provided a blood specimen (confidential results), and completed structured questionnaires that assessed emotional reactions to potentially being a premutation carrier (pretest questionnaire, n = 20) and the posttest known carrier status (3 month follow-up questionnaire, n = 18 non-carriers). Responses were measured using 9-point scales, and analyzed with Fisher exact and Wilcoxon exact tests. While most participants did not view fragile X premutations as a serious medical condition, perceptions of seriousness were positively correlated with anger and regret about not knowing sooner of the potential association of these premutations with infertility. Overall, when women (pretest) imagined themselves as carriers, their self-esteem and Health Orientation Scale responses were unchanged with the exception of feeling more afraid (p = 0.004). Despite strongly wishing for negative test results, they were glad to know there might be a medical explanation for their infertility.
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PMID:Emotional reaction to fragile X premutation carrier tests among infertile women. 1796 39

Premature ovarian failure (POF) occurs in 1% of the general population and affects approximately 10% of non-ovulating women, resulting in infertility and sex steroid deficiency. The forkhead domain transcription factor (FOXL2) gene is one of the candidate genes associated with POF. This case-control study was designed for mutational analysis of the coding region of the FOXL2 gene in 80 cases of POF patients, 50 controls and 17 family members of 11 index cases using restriction fragment length polymorphism, single-stranded conformational polymorphism, heteroduplex analysis and direct DNA sequencing. A 738C-->T transition and a 773C-->G transversion were detected in two of the 80 patients and a family member of one index case, but in none of the 50 controls screened. No other alterations in the coding region of FOXL2 gene were detected. These data suggest that FOXL2 gene mutations are a rare occurrence in isolated POF cases and may not be involved in the pathogenesis of POF.
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PMID:Screening for FOXL2 gene mutations in women with premature ovarian failure: an Indian experience. 1802 47

The immune system, besides orchestrating the immune response, plays an important role in the regulation of tissue homeostasis. We refer to this later activity as 'immune physiology.' In human ovaries, immune system-related cells and molecules accompany corpus luteum development and regression and cancer progression. They also accompany the origination of new rat and human germ cells by asymmetric division of ovarian surface epithelium cells, symmetric division and migration of germ cells, and follicular growth. Currently prevailing dogma on the preservation of human oocytes from the fetal period until menopause ('storage' doctrine) vs. oocyte renewal in invertebrates and lower vertebrates ('continued formation' doctrine) raises question as to the disadvantage from an evolutionary point of view of prolonged oocyte storage in humans. We attempted to reconcile these two opposing views by proposing the prime reproductive period (PRP) doctrine as follows: The 'storage' doctrine fits two periods of the life in human females, that between the termination of fetal oogenesis and puberty or pre-menarcheal period (about 10-12 years), and also that period from the end of PRP (at about 38 years of age) until menopause. On the contrary, the 'continued formation' doctrine accounts for oocyte and follicular renewal during the PRP, and insures the availability of fresh oocytes for the development of healthy progeny. Further study on 'immune physiology' may help us better understand ovarian physiology and pathology in general, including infertility caused by premature ovarian failure, the pathophysiology of degenerative diseases and mechanisms of malignancy and metastasis.
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PMID:Immune physiology of the mammalian ovary - a review. 1815 92

Premature ovarian failure (POF) is a common pathology leading to infertility affecting about 1% of women under 40 years old. In POF patients, the ovarian dysfunction is characterized by the lack of the ovarian response to close a negative feedback loop on the synthesis of pituitary gonadotropins. Although the majority of cases are considered as idiopathic, diverse aetiologies have been associated, including genetic factors. Up to now, the potential genetic causes of non-syndromic POF have been established mainly by genetic linkage analysis of familial cases or by the screening of mutations in candidate genes based on animal models. Here, we review recent advances in the study of candidate genes.
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PMID:Recent advances in the study of genes involved in non-syndromic premature ovarian failure. 1816 39


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