Premature Ovarian Failure

Premature ovarian failure (POF), that is, amenorrhea before 40 years of age can be attributed to a variety of etiologies. Approximately 1% of women before 30 years are diagnosed with POF. Spontaneous ovulation leading to pregnancy in POF is even a rarer entity. We ...

In this prospective randomized study, women with idiopathic karyotypically normal premature ovarian failure (POF) were treated with gonadotrophin-releasing hormone (GnRH) agonist and gonadotrophins with and without the addition of corticosteroids in an attempt to restore ovarian function. The study comprised 58 women with idiopathic POF randomly allocated to either GnRH agonists (GnRHa) plus gonadotrophin therapy with the addition of corticosteroids (29 patients) or GnRHa plus gonadotrophin therapy with placebo (29 patients). Ovulation occurred in six cases (20.7%) in the dexamethasone group versus three cases (10.3%) in the placebo group. There were two singleton pregnancies in the dexamethasone group. There were no reported complications from the use of dexamethasone apart from a sense of sleepiness and fatigue. The combination of corticosteroids with pituitary suppression followed by ovarian stimulation with gonadotrophin appeared to be beneficial in restoring ovarian function in patients with idiopathic POF and normal karyotype.

The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries may cause an accumulation of spontaneously arising or environmentally induced genetic alterations of oocytes, and that may be why aging females have a much higher chance of having oocytes with more mutations in persisting primary follicles.

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

To examine the relationship between spiritual well-being and functional well-being in women who have spontaneous premature ovarian failure. Cross-sectional. The Mark O. Hatfield Clinical Research Center at the US National Institutes of Health. Women diagnosed with spontaneous premature ovarian failure (N = 138) at a median age of 28 years. Administration of validated self-reporting instruments. Functional Well-Being, Spiritual Well-Being, Meaning/Peace, and Faith scores. We found a significant positive correlation between overall spiritual well-being and functional well-being scores. The Meaning/Peace subscale strongly correlated with functional well-being, explaining approximately 62% of the variance. In contrast, the Faith subscale was less strongly correlated with functional well-being, explaining only 7% of the variance. In multiple regression analysis evaluating the relative subscale contributions to functional well-being, only Meaning/Peace remained statistically significant. We found no significant associations between either spiritual well-being or functional well-being and age; age at diagnosis; time since diagnosis; or partner, children, or racial status. This study provides cross-sectional data supporting the need for prospective controlled studies. Strategies to improve spiritual well-being in the domains of meaning, purpose, and inner peace may provide a therapeutic approach to reduce the emotional suffering that accompanies the life-altering diagnosis of premature ovarian failure.

OBJECTIVE:
The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many genetic perturbations are also on the autosomes. The aim of this review is to summarize the knowledge of genetic aberrations on autosomes from chromosomal rearrangement, gene abnormality, genome-wide association studies and epigenetics.
METHODS:
Searches of electronic databases were performed. Articles and abstracts relevant to POI and genetic studies associated with autosomes were summarized in this interpretive literature review.
RESULTS:
Various genetic aberrations located on the autosomes were found. These abnormalities are from chromosomal rearrangement, which might disrupt the critical region on chromosome loci or disturbance of the meiosis process. Specific gene aberrations are also identified. The genes that have functions in ovarian development, folliculogenesis, and steroidogenesis on autosomes are proposed to be involved from gene association studies. Gene-to-gene interaction or epistasis also might play a role in POI occurrence. Recently, genetic techniques to study the whole genome have emerged. Although no specific conclusion has been made, the studies using genome-wide association to find the specific aberration throughout the genome in POI have been published. Epigenetic mechanisms might also take part in the pathogenesis of POI.
CONCLUSIONS:
The considerably complex process of POI is still not well understood. Further research is needed for gene functional validation studies to confirm the contribution of genes in POI, or additional genome-wide association studies using novel clustered regularly interspaced short palindromic repeat/Cas9 technique might make these mechanisms more comprehensible.

Premature ovarian failure (POF) is a heterogeneous syndrome, possibly due to mutations of genes involved in the normal development of the ovary and/or the follicles. Based essentially on animal models, these mutations are associated with various ovarian histological phenotypes, from a complete absence of to a partial follicular maturation. The aims of our work were in one hand to determine if ovarian histology, compared to pelvic ultrasonography, would be helpful either in identifying which patients display an impaired follicular growth or in the orientation of the POF etiology; on the other hand, since developing follicles up to the antral stage are reported in POF and that Anti-Müllerian hormone (AMH) might be a good indicator of follicular presence, we decided to determine whether AMH should be a better marker to determine the presence of an ovarian reserve in POF patients. To try to answer to the first question, we studied first 166 patients suffering from POF with a normal kary...

Introduction: Stem cells (sc) are the foundation cells for every organ, tissue and cell in the body. They are self sustaining and can replicate themselves for long periods of time. Stem cells can differentiate into different types of cells. Women below the age of forty and showing ovarian function loss are defined to have premature ovarian failure (POF). It is associated with sex steroid deficiency, amenorrhea, infertility, and elevated serum gonadotropins.
Aim: To evaluate the therapeutic potential of autologous Mesenchymal sc (MSC) transplantation in women suffering from POF. Out of 112 high risk patients for POF(cases with amenorrhoea befor the age of forty), diagnosis was confirmed in10 cases. The ten POF patients were scheduled for MSC transplantation at Al- Azhar University Hospitals. MSC preparation from the bone marrow of the iliac crest was laparoscopically injected into the ovaries. Endometrial fractional biopsy was histopathologicaly (HP) and Immunohistochemically (IH) stained and evaluated according to Edessy stem cells score (ESS). Ovarian reserve was evaluated according to Edessy ovarian reserve score (EORS). Results: Showed that after transplantation two cases (20%) (ESS = 5 and 6) resumed menstruation after 3 months, one of them (10%) (Case no 5) (ESS = 6) got pregnancy after 11 months and delivered a healthy full term baby (Zeinab).Ten months after transplantation EORS of patient who developed pregnancy (case no 6) was found to be 7 after being 0 before therapy. EORS of the other menstruating case (case no 10) was 5 after being 0. The 2 menstruating cases showed focal secretory changes after being atrophic endometrium in case 5 and distorted proliferative endometrium in case 10. Conclusion: Stem cell transplantation is a good procedure and regarded as a real and hope to get healthy pregnancy and baby for cases ofPOF. It showed good clinical, HP and IH outcome

To determine whether perturbations of the growth differentiating factor-9 (GDF9) gene are associated with premature ovarian failure (POF). Mutational analysis of the GDF9 gene in 61 women with POF. Academic institution. Sixty-one women with POF; 60 control women. Peripheral blood sampling, genomic DNA extraction, mutational screening, and DNA sequencing. Genetic perturbations in GDF9 that are associated with POF. A single missense mutation, substitution of a cytosine residue with thymidine in exon 1 of GDF9, was found in a white woman in whom POF developed at age 22. This mutation occurred in a highly conserved proprotein region and resulted in replacement of a nonpolar amino acid (proline) with a polar amino acid (serine) at position 103. Neither 60 control women nor 60 other women with POF demonstrated this genetic perturbation. Exon 2 showed only previously recognized single nucleotide polymorphisms. GDF9 mutations may be one explanation for POF, albeit uncommon.

We report a case of pelvic organ prolapse quantification (POPQ) stage III uterine prolapse in a 25-year-old nulligravida. Premature ovarian failure was diagnosed after 1 year of amenorrhea. Localized scleroderma was noticed on her thigh and lower back. We discuss the possible role of scleroderma and ovarian failure on the occurrence of uterine prolapse in light of the literature.

Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes in a population with premature ovarian failure (POF) identified no new mutations. However, three single nucleotide polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and 71C>G) and another in exon 1 (387G>A), were found to be common in both POF and control groups.