Primary Ovarian Insufficiency due to Steroidogenic Cell Autoimmunity Is Associated with a Preserved Pool of Functioning Follicles

Mother-Infant Department, Section of Obstetrics and Gynecology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 08/2009; 94(10):3816-23. DOI: 10.1210/jc.2009-0817
Source: PubMed


Primary ovarian insufficiency (POI) is defined as hypergonadotropic amenorrhea before the age of 40 yr. In 4-5% of patients with POI, an ovarian autoimmune process is present.
Serum concentrations of antimüllerian hormone (AMH) have been determined in 26 women with POI due to steroidogenic cell autoimmunity (SCA-POI), 66 with nonautoimmune idiopathic POI (iPOI), 40 postmenopausal women (PMW), and 44 healthy fertile women (HW). SCA-POI was diagnosed according to presence of steroidogenic enzyme autoantibodies (17alpha-hydroxylase, side chain cleavage, and 21-hydroxylase autoantibodies).
AMH concentrations were significantly higher in women with SCA-POI than women with iPOI (P = 0.018) or PMW (P = 0.03) but significantly lower than HW (P < 0.0001). AMH was detected in 11 of 26 women with SCA-POI (42%) and seven of 66 with iPOI (11%) (P = 0.002). Serum concentrations above the fifth percentile of the normal range (0.6 ng/ml) were detected in nine of 26 women with SCA-POI (35%) and four of 66 with iPOI (6%) (P = 0.001). Eight of 12 women with SCA-POI with less than 5 yr (67%) and one of 14 with longer disease duration (7%) had AMH concentrations within the normal range (P = 0.003). AMH concentrations correlated inversely with disease duration in women with SCA-POI (rho = -0.563, P = 0.003) but not women with iPOI. AMH correlated inversely with FSH serum concentrations in HW (rho = -0.584, P < 0.001) but not PMW or women with POI.
Two thirds of women with recent-onset SCA-POI had normal AMH concentrations. Women with SCA-POI, differently from those with iPOI, present a preserved ovarian follicle pool for several years after diagnosis of ovarian insufficiency.

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    • "In contrast, AMH levels are undetectable in the great majority of women diagnosed with primary ovarian insufficiency (POI) (WHO group 3) suggesting premature follicle pool exhaustion (Knauff et al., 2009). Moreover, AMH may provide useful information regarding the extent of follicle pool depletion in various POI-like conditions, such as incipient ovarian failure (Knauff et al., 2009), ovarian failure due to autoimmunity (La Marca et al., 2009) or FSH receptor loss of function mutation (Kallio et al., 2012). In this context, it should be noted that current criteria used to define POI (such as FSH concentrations .40 "
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    ABSTRACT: BACKGROUND In women, anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells of ovarian follicles during the early stages of follicle development. After an initial increase until early adulthood, AMH concentrations slowly decrease with increasing age until becoming undetectable ∼5 years before menopause when the stock of primordial follicles is exhausted. However, major individual variability exists in the pace of follicle pool depletion and the initial size of the follicle pool, reflected by a wide range of age at menopause. Individual AMH serum concentration does accurately reflect the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles. Accordingly, AMH levels may vary significantly in women of the same chronological age, allowing AMH to predict the remaining length of a woman's reproductive lifespan.
    Human Reproduction Update 05/2014; 20(5). DOI:10.1093/humupd/dmu020 · 10.17 Impact Factor
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    • "We recently documented normal serum AMH concentrations in two-thirds of women with recently diagnosed autoimmune POI (La Marca et al, 2009), which provides the first demonstration of the existence of a subgroup of women with POI with a preserved ovarian follicle pool for several years. Since AMH is the best biochemical marker of residual follicle pool, the results of our study (La Marca et al, 2009) are highly relevant for the future planning of clinical trials of immunotherapy aimed at preserving the residual functional tissue and/or delay the progression of the destructive ovarian autoimmune process in women with autoimmune POI. "

    Contemporary Aspects of Endocrinology, 11/2011; , ISBN: 978-953-307-357-6
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    • "Even POF/POI, and in physiologic menopause ovaries still contain substantial numbers of NGFs. A form of POF/POI, characterized by steroidogenic cell autoimmunity, demonstrates almost uniformly preserved follicle pools on ultrasound [28]. Indeed, in the past considered a rare finding, follicles can be seen on ultrasound in over a third of POF/POI cases [42]. "
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    ABSTRACT: Though a widely utilized term and clinical concept, ovarian reserve (OR) has been only inadequately defined. Based on Medline and PubMed searches we here define OR in its various components, review genetic control of OR, with special emphasis on the FMR1 gene, and discuss whether diminished OR (DOR) is treatable. What is generally referred to as OR reflects only a small portion of total OR (TOR), a pool of growing (recruited) follicles (GFs) at different stages of maturation. Functional OR (FOR) depends on size of the follicle pool at menarche and the follicle recruitment rate. Both vary between individuals and, at least partially, are under genetic control. The FMR1 gene plays a role in defining FOR at all ages. Infertility treatments have in the past almost exclusively only centered on the last two weeks of folliculogenesis, the gonadotropin-sensitive phase. Expansions of treatments into earlier stages of maturation will offer opportunity to significantly improve ovarian stimulation protocols, especially in women with DOR. Dehydroepiandrosterone (DHEA) may represent a first such intervention. Data generated in DHEA-supplemented women, indeed, suggest a new ovarian aging concept, based on aging of ovarian environments and not, as currently is believed, aging oocytes.
    Reproductive Biology and Endocrinology 02/2011; 9(1):23. DOI:10.1186/1477-7827-9-23 · 2.23 Impact Factor
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