Primary ovarian insufficiency: Autoimmune causes

Mother-Infant Department, Section of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy.
Current opinion in obstetrics & gynecology (Impact Factor: 2.07). 08/2010; 22(4):277-82. DOI: 10.1097/GCO.0b013e32833b6c70
Source: PubMed


To review the pathogenesis of premature ovarian insufficiency due to steroid cell autoimmunity (SCA-POI).
Autoimmune oophoritis is characterized by a selective mononuclear cell infiltration into the theca layer of large, antral follicles, with earlier stage follicles consistently free of lymphocytic infiltration. SCA-POI is caused by the selective autoimmune destruction of theca cells with preservation of granulosa cells that produce low amounts of estradiol because of lack of substrates. Typically, serum concentrations of inhibins are increased in women with SCA-POI, as compared to both healthy fertile women and women with other forms of ovarian insufficiency. Normal serum antimüllerian hormone (AMH) concentrations were detected in two-thirds of women with recently diagnosed SCA-POI, which demonstrates that this form of ovarian insufficiency is associated with a preserved pool of functioning follicles.
The combined measurement of autoantibodies and markers of ovarian reserve (as inhibin B and AMH) may permit to identify women with POI due to steroid cell autoimmunity with a preserved proportion of primordial and primary follicles. In the future the development of techniques of in-vitro folliculogenesis may permit new treatment strategies for women with SCA-POI-related infertility.

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Available from: Antonio La Marca, Oct 09, 2015
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    • "Besides, a high correlation between POR and the presence of ovarian auto-antibody was seen (52, 53). These autoimmune responses primarily targets theca and granulosa cells (54), yielding dramatically reduced FSH receptor (FSHR) in POR. In a previous study, it has been shown that relative quantity of FSHR is positively correlated with two markers of ovarian response including number of mature oocytes and the peak level of serum E2 (3). "
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    ABSTRACT: Background: Poor ovarian response (POR) to gonadotropin stimulation has led to a significant decline in success rate of fertility treatment. The immune system may play an important role in pathophysiology of POR by dysfunctions of cytokines and the growth factor network, and the presence of ovarian auto-antibodies. The aim of this study is to investigate the expression of toll-like receptors (TLR) 1, 2, 4, 5, 6 and cyclooxygenase (COX) 2 genes in follicular cells and concentration of interleukin (IL)-6, IL-8 and macrophage migration inhibitory factor (MIF), as major parts of innate immunity, in follicular fluid (FF) obtained from POR women in comparison with normal women. Materials and methods: In this case-control study, 20 infertile POR patients and 20 normal women took part in this study and underwent controlled ovarian stimulation. The FF was obtained from the largest follicle (>18 mm). The FF was centrifuged and cellular pellet was then used for evaluation of expression of TLRs and COX2 genes by real-time PCR. FF was used for quantitative analysis for IL-6, IL-8 and MIF by enzyme-linked immunosorbent assay (ELISA). Results: TLR1, 2, 4, 5, 6 and COX2 gene expression were significantly higher in POR (p<0.05). Concentration of IL-6, IL-8 and MIF proteins was significantly increased in POR compared with normal women (p<0.05). Conclusion: These findings support the hypothesis that the immune system may be involved in pathophysiology of POR through TLRs.
    International journal of fertility & sterility 07/2014; 8(2):183-92. · 0.47 Impact Factor
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    • "Substantial evidence from a number of sources demonstrates serum AMH levels are associated with other diseases. For example, AMH is significantly lower in autoimmune disorders [64] such as lupus [65▪▪,66] and Crohn's disease [67▪]. Elevated AMH levels can also be useful in postmenopausal women as a strong indicator of granulosa cell tumors (GCTs) and for monitoring for the recurrence of GCTs, though in asymptomatic, premenopausal women, elevated AMH is too nonspecific for clinical utility as a screening test for these tumors [68,69]. "
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    ABSTRACT: Purpose of review To provide an update on the latest clinical applications of serum antimüllerian hormone (AMH) testing with practical approaches to mitigate the impact of significant variability in AMH results. Recent findings Recent studies continue to demonstrate that AMH is the best single serum test for ovarian response management with, at most, a weak-to-moderate age-independent association with live-birth rate and time to conception. Data confirm serum AMH levels improve menopause prediction, monitoring of ovarian damage, and identification of women at risk for several ovary-related disorders such as polycystic ovary syndrome and premature or primary ovarian insufficiency. However, it is now recognized that serum AMH results can have dramatic variability due to common, biologic fluctuations within some individuals, use of hormonal contraceptives or other medications, certain surgical procedures, specimen treatment, assay changes, and laboratory calibration differences. Practical guidelines are provided to minimize the impact of variability in AMH results and maximize the accuracy of clinical decision-making. Summary AMH is an ovarian biomarker of central importance which improves the clinical management of women's health. However, with the simultaneous rapid expansion of AMH clinical applications and recognition of variability in AMH results, consensus regarding the clinical cutpoints is increasingly difficult. Therefore, a careful approach to AMH measurement and interpretation in clinical care is essential.
    Current Opinion in Obstetrics and Gynecology 06/2014; 26(4). DOI:10.1097/GCO.0000000000000087 · 2.07 Impact Factor
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    • "We thought that this was the reason we could not find lymphocytic and plasma cell infiltration representing AO. However, it has been recently reported that lymphocytic and plasma cell infiltration may be absent and selective mononuclear cell infiltration free of lymphocytes may be observed in AO (23). Antibodies against steroid cell antigens obtained from adrenal tissue substrates are the most validated marker for the diagnosis of APOF that correlates with ovarian inflammation (7). "
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    ABSTRACT: Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies against acetylcholine receptors. MG is generally an isolated disorder but may occur concomitantly with other autoimmune diseases. We describe an eighteen-year-old girl with MG who was admitted to our clinic with secondary amenorrhea and diagnosed as autoimmune oophoritis. Since her myasthenic symptoms did not resolve with anticholinesterase therapy, thymectomy was performed. After thymectomy, her menses have been regular without any hormonal replacement therapy. To our knowledge, this is the first report on a patient with autoimmune ovarian insufficiency and MG in whom premature ovarian insufficiency resolved after thymectomy, without hormonal therapy. Conflict of interest:None declared.
    Journal of Clinical Research in Pediatric Endocrinology 12/2011; 3(4):212-5. DOI:10.4274/jcrpe.378
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