Autoimmunity in premature ovarian failure.

We performed laparoscopic ovarian biopsies in 17 of 19 cases with premature ovarian failure. Primordial follicles were found in three cases, corpora albicanti in two, and epithelial-lined cysts in two cases. Chromosome analysis revealed a normal 46XX karyotype in 15 patients, 46XY in two, 45XO in one, and 46XO/46XX mosaicism in one patient. Immunofluorescence studies were performed on ovarian tissue obtained by laparoscopic biopsy in 12 cases with premature ovarian failure. Blood serum was analyzed for circulating anti-ovary and other autoantibodies in all 12 cases. Circulating autoantibodies were found in the serum of six patients, but not in healthy controls. Direct immunofluorescence was positive in 5 of 12 ovarian tissue samples with predominantly vascular wall staining. Indirect immunofluorescence was positive in 10 of 12 cases; antibodies reacting with ovarian stromal components were present in eight cases, antibody reacting with follicular epithelium was present in one case, and antibodies reacting with nuclear antigens were present in five cases. Two of the patients had anti-thyroid microsomal antibodies, and one had antitesticular antibody. We conclude that a significant number of patients with ovarian failure have serologic and biopsy findings suggestive of and consistent with autoimmunity, even though there are no overt clinical manifestations of autoimmune disease.     

Poland's syndrome and premature ovarian failure

A 19-year-old female with Poland's Syndrome with associated left amastia, scoliosis, and left Sprengel deformity developed secondary amenorrhea from premature ovarian failure. Her menarche was at 13 years of age, and periods were regular and monthly until 15 years of age when her periods suddenly stopped. Her hormonal evaluation was significant for elevated FSH (46.5 mIU/ml) and LH (28.5 mIU/ml), and low estradiol (23 pg/ml). Anti-ovarian antibody level was less than 2 units (normal < 4 units). Her chromosomes were 46XX, by both standard karyotype and by fluorescence in situ hybridization. On transabdominal and transvaginal ultrasonography, ovaries were not visualized, the uterus was of normal size and anteverted and both kidneys were normal. The patient began hormone replacement therapy with conjugated estrogen (Premarin) 0.625 mg po daily and progestin (Provera) 5 mg on days 20 to 25. Because of menopausal symptoms, she was switched to a combination oral contraceptive (OC) with 20 mcg ethinyl estradiol that was eventually increased to 30 mcg. Her menopausal symptoms (hot flashes and sweating) improved on the continuous 30 mcg ethinyl estradiol combination OC. Following a comprehensive review of the literature, this is the first reported case of Poland's Syndrome associated with premature ovarian failure; however, this association may be coincidental.     

Incidence of premature ovarian failure

To assess the occurrence of premature ovarian failure, the age-specific incidence rates of natural menopause were determined for a cohort of 1858 women born between 1928 and 1932. These women were identified as Rochester, Minnesota residents in 1950 and were followed for date and type of menopause. A total of nine experienced natural menopause before age 40 years, which represents a 1% risk of natural menopause to age 40. The annual incidence rates of natural menopause per 100,000 person-years were ten for ages 15 to 29 and 76 for ages 30 to 39. In the age group 40 to 44, the incidence of natural menopause increased greatly to 881 per 100,000 person-years at risk.     

原发性卵巢功能不全与卵巢早衰的病因学研究进展

目前,卵巢早衰(premature ovarian failure,POF)是被广泛接受和应用的专业术语,通常是指女性40岁之前闭经,伴有高卵泡刺激素(FSH)和低雌激素水平.由于临床治疗很棘手,如何预防和预测POF的发生风险,成为临床医生关注的焦点.尽管在POF发病机制的探讨中,染色体结构或数目异常、自身免疫功能、医源性及环境等相关因素与POF发病的相关性研究已取得很大进展,但仍有部分POF患者的病因不清,称为"特发性POF".     

X chromosome genes and premature ovarian failure

Premature ovarian failure (POF) is a disorder characterized by lack of ovulation and elevated levels of serum gonadotropins before the age of 40. The etiology of POF is not known but different environmental and genetic factors are involved, suggesting high heterogeneity of the disorder. The involvement of X-linked genes in the etiology of POF was hypothesized on the basis of its frequent association with chromosomal rearrangements and monosomies. In recent years a number of genes were described. Two genes, FRAXA and POF1B, have been formally demonstrated to be responsible for POF. Other genes have been proposed as candidates, but their role remains to be demonstrated.     

Genetic basis of premature ovarian failure

Patients' perception of family life after a multiple birth: euphoria or Pandora's box? The aim of this article is to explore the realities of parenting children from a multiple pregnancy as an aid to decision-making about the number of embryos transferred. Outcome research regarding parenting of children from twin, triplet and higher order births is described and, in particular, children of multiple births from assisted reproductive technology. Current understanding of interpersonal relationships in multiple birth families is also discussed. The evidence from these various sources is put in the framework of social risk factors as an aid to predicting outcomes and as an essential part of decision-making with the full participation of patients. The implications of such an approach is presented in relation to support for such families. Case studies are included of three triplet families. Reference is made to fetal reduction as an option.     

自噬机制与卵巢早衰的关系

细胞自噬是哺乳动物细胞物质代谢的一种重要机制,细胞自噬异常将导致细胞功能异常甚至死亡。细胞自噬异常在卵巢早衰(POF)的发病中扮演着重要的角色,细胞自噬与细胞凋亡之间存在着许多分子联系,凋亡相关蛋白Bcl-2、Caspase与自噬相关蛋白Beclin-1互相作用,可以引起卵巢发育异常;凋亡蛋白Bim、Fas与自噬相关信号通路PTEN-PI3K及下游转录因子Fox O蛋白互相作用,可以导致卵巢卵泡激活异常;激素异常通过TGF-β/Smad3通路介导凋亡和自噬相关蛋白异常,导致卵泡闭锁,从而可以导致POF的发病。细胞自噬极有可能与细胞凋亡一起,是POF的主要发病机制。     

Diagnostic and clinical status of premature ovarian failure

Premature Ovarian Failure is a heterogeneous disorder with numerous causes. The exact prevalence of POF is unknown. In this study, we want to make Differentiate diagnosis of hypergonadotropic amenorrhea and to determine the difference between them. Retrospective, we follow up 475 women at which we perform ovarian stimulation and we observe that 6 (1.3%) have Gonadotropin resistant ovary syndrome in IVF-centre--MU--Varna.     

The lived experience of premature ovarian failure

OBJECTIVE: To describe the lived experience of women who have been diagnosed with idiopathic premature ovarian failure (POF). DESIGN: Phenomenology was used to achieve the purpose. Women were asked to share their experiences in living with premature ovarian failure during an approximately 1-hour interview. The interviews were tape-recorded, transcribed, and analyzed for emergent themes. SETTING: Interviews were conducted in the participants' homes and in a conference room in a hospital. PARTICIPANTS: The six participants were drawn from a multicultural sample of women with idiopathic POF. RESULTS: The women in this study expressed anger at their health care providers for their perceived lack of quality care they had experienced and at the insurance industry for its lack of reimbursement for fertility interventions; they expressed depression and sadness at the prospective outcome of the diagnosis, mixed emotions regarding their significant others, and sadness and resignation about their menopausal symptoms. CONCLUSIONS: Health care providers who create an environment in which women and their significant others will feel supported in asking questions, be assured that their concerns are taken seriously, and be provided with the physical and emotional resources they need can help these women to continue to build and live their lives.     

The genetic basis of premature ovarian failure

Premature ovarian failure (POF) is a common condition, affecting approximately 1:100 women. It is characterised by amenorrhea, hypoestrogenism, and elevated gonadotrophin levels in women under the age of 40. It is often an unexpected and distressing diagnosis, which coincides with infertility and menopausal symptoms. There is a well recognised genetic basis to the development of POF. Our laboratory has identified several candidate genes associated with POF.     

The genetic basis of premature ovarian failure

Premature ovarian failure is defined by the association of amenorrhea, elevated levels of serum gonadotropins and hypoestrogenism occuring before the age of forty. In a growing number of these cases, genetic disorders have been shown to be involved. Cytogenetic abnormalities predominantly concern the X chromosome, including Turner syndrome, but also rearrangements such as deletions and X-autosome translocations. Molecular investigation of these abnormalities has led to the identification of a number of candidate genes most of them still having unknown functions. Testing for premutation of the FMR1 gene, whose full mutation determines the fragile X syndrome, is particularly worthwhile in these patients because of its high frequency, not only among the patients with ovarian failure but also in the general population. Other, much less frequent mutations have been located for example in the gonadotropin and gonadotropin receptor genes and their study contributes to the understanding of ovarian physiology. Here we review most of the etiologies which have to be taken in account in the genetic screening of premature ovarian failure patients.     

卵巢早衰的遗传学研究进展

卵巢早衰(POF)是一种临床高度异质且病因复杂的疾病,遗传因素是其重要的发病原因。遗传因素主要包括X染色体、常染色体异常、微小RNA表达异常等。全基因组关联研究(GWAS)、高通量测序(NGS)技术等迅猛发展,可对基因标志物或核苷酸多态性进行统计分析,发现其间的内部联系,揭示新的致病基因,为POF的遗传学基础研究提供崭新的平台。     

卵巢早衰治疗策略探讨

目的　评价性激素替代治疗 (hormonereplacementtreatment,HRT)对卵巢早衰 (prematureovarianfail ure ,POF)患者的疗效 ,探讨卵巢早衰可能有效的促排卵方案。方法　采用前瞻性研究方法对 19例卵巢早衰患者 ,行HRT共 3～ 6个周期 ,观察服药前后临床症状、盆腔超声相、血清生殖激素变化及停药后卵泡发育情况 ,并对个别患者行促排卵治疗观察疗效。结果　 19例患者经HRT临床症状明显缓解。与服药前比较 ,血清卵泡刺激素 (FSH)水平明显下降 (P <0 0 1) ,血清黄体生成素 (LH)水平显著下降 (P <0 0 5 )。双侧卵巢及子宫体积无显著变化 (P >0 0 5 ) ,子宫内膜明显增厚 (P <0 0 1)。停药后 1例自然妊娠 ,1例自发排卵 ,1例用促性腺激素释放激素激动剂 (GnRHa) /绝经期促性腺激素 (HMG) /绒毛膜促性腺激素 (HCG)治疗有排卵。服药期间无肝功能损伤及其它副反应。结论　性激素替代治疗卵巢早衰 3～ 6个周期 ,可使临床症状缓解 ,血清FSH、LH明显下降 ,利于促排卵治疗成功。     

Circulating antiovarian antibodies in premature ovarian failure

The presence of antiovarian antibodies in sera of women with premature ovarian failure was determined by an indirect fluorescent antibody assay using human ovarian tissue. Of 27 patients, 14 had positive ovarian fluorescence, compared with zero of 24 normal cycling controls (P less than .001) and one of 22 postmenopausal controls (P less than .01). In patients with autoimmune diseases, five of 17 demonstrated positive fluorescence compared with zero of 24 premenopausal controls (P less than .01). Immunoperoxidase staining revealed antigen concentrated at the granulosa cells and oocyte in nine of the 14 ovarian failure cases. The finding that a significant proportion of patients with premature ovarian failure have circulating antiovarian antibodies confirms previous studies, but localization of peroxidase staining to granulosa cells and/or oocytes represents a new finding in this study.