Special Issue "Pathogenesis, Diagnosis and Therapy of Ovarian Disorders and Infertility"

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Therapeutic Strategies in Different Diseases".

Deadline for manuscript submissions: closed (31 October 2018).

Special Issue Editor

Prof. Ayman Al-Hendy
Website
Guest Editor
Division of Translational Research, Department of Obstetrics and Gynecology, University of Illinois/Chicago (UIC), 820 South Wood Street, 2nd Fl (M/C 808), Chicago, IL 60612, USA
Interests: premature ovarian insufficiency; premature ovarian failure; polycystic ovary syndrome; genetics; diagnosis; ovarian function; IVF; egg donation; gene therapy; stem cell therapy; hormone replacement therapy; patient perspective

Special Issue Information

Dear Colleagues,

Diseases of the ovary which most frequently cause infertility are: chronic anovulation syndromes, within which polycystic ovary syndrome plays a major role, and premature ovarian insufficiency (POI). In this special issue, we will provide the readers with an update of this broad cluster of disorders that negatively affect women’s ability to accomplish a pregnancy with an intentional focus on POI. Premature ovarian insufficiency (POI), also known as premature ovarian failure (POF), is defined as hypergonadotropic ovarian failure occurring prior to 40 years of age. It is surprisingly common and affects approximately 1% of women below 40 years of age. The incidence is 10% to 28% in women with primary amenorrhea and 4% to 18% in women with secondary amenorrhea. Affected women often face this devastating disease suddenly and start to endure a diagnosis of irreversible infertility at a young age. Many learn to live with great uncertainty about their ability to create a family—a core identity issue for many women from various cultural, religious and ethnic backgrounds. The majority of patients with POI/POF are considered to have idiopathic premature ovarian failure because usually no cause can be identified. Recent advances in understanding the etiology of POI/POF are encouraging. Clearly, the more we learn about the molecular events of early ovarian folliculogenesis, follicular atresia, ovarian stem cell biology and egg maturation, the more we can envision innovative therapeutics for POI/POF patients. Along these lines, early attempts at gene and stem cell therapy for POI/POF in preclinical models and in patients also show some promise.  In this Special Issue, we want to present the most current and cutting edge information on the etiology, pathogenesis and therapy of POI/POF. We anticipate that this Special Issue will therefore be an excellent contribution to the field and will constitute an up-to-date modern practical reference for OB/GYNs, reproductive medicine specialists, primary care practitioners and any clinician, nurse or health care worker caring for women living with POI/POF.

Prof. Ayman Al-Hendy
Guest Editor

Manuscript Submission Information

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Keywords

  • Premature ovarian insufficiency
  • Premature ovarian failure
  • Polycystic ovary syndrome
  • Chronic anovulation
  • Genetics, diagnosis
  • Ovarian function
  • IVF
  • Egg donation
  • Gene therapy
  • Stem cell therapy
  • Hormone replacement therapy
  • Patient perspective

Published Papers (5 papers)

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Research

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Open AccessArticle
Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency
Biomedicines 2019, 7(1), 7; https://doi.org/10.3390/biomedicines7010007 - 18 Jan 2019
Cited by 3
Abstract
Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control [...] Read more.
Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials. Full article
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Open AccessArticle
Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure
Biomedicines 2018, 6(3), 93; https://doi.org/10.3390/biomedicines6030093 - 15 Sep 2018
Cited by 2
Abstract
Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of [...] Read more.
Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. In addition, CTX decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR (steroidogenic acute regulatory protein), and Connexin-43 protein expression in the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (p < 0.05). When both CTX and untreated control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (p < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells. Full article
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Review

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Open AccessReview
Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility
Biomedicines 2019, 7(1), 5; https://doi.org/10.3390/biomedicines7010005 - 04 Jan 2019
Cited by 2
Abstract
The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. [...] Read more.
The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. Group II disorders display a eugonadal state commonly associated with a wide range of endocrinopathies. Finally, group III constitutes hypergonadotropic hypogonadism secondary to depleted ovarian function. Optimal evaluation and management of these disorders is based on a careful analysis tailored to each patient. This article reviews ovulation disorders based on pathophysiologic mechanisms, evaluation principles, and currently available management options. Full article
Open AccessReview
Premature Ovarian Insufficiency: Procreative Management and Preventive Strategies
Biomedicines 2019, 7(1), 2; https://doi.org/10.3390/biomedicines7010002 - 28 Dec 2018
Cited by 1
Abstract
Premature ovarian insufficiency (POI) is the loss of normal hormonal and reproductive function of ovaries in women before age 40 as the result of premature depletion of oocytes. The incidence of POI increases with age in reproductive-aged women, and it is highest in [...] Read more.
Premature ovarian insufficiency (POI) is the loss of normal hormonal and reproductive function of ovaries in women before age 40 as the result of premature depletion of oocytes. The incidence of POI increases with age in reproductive-aged women, and it is highest in women by the age of 40 years. Reproductive function and the ability to have children is a defining factor in quality of life for many women. There are several methods of fertility preservation available to women with POI. Procreative management and preventive strategies for women with or at risk for POI are reviewed. Full article
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Open AccessReview
The Role of Gene Therapy in Premature Ovarian Insufficiency Management
Biomedicines 2018, 6(4), 102; https://doi.org/10.3390/biomedicines6040102 - 01 Nov 2018
Cited by 2
Abstract
Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before the age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g.; anticancer treatment, genetic disorders, and enzymatic defects) could be [...] Read more.
Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before the age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g.; anticancer treatment, genetic disorders, and enzymatic defects) could be identified. Although hormone-replacement therapy, the principal therapeutic approach for POI, helps alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, an effective approach to manage patients with POI is highly warranted. Several mechanisms associated with POI have been identified, including the lack of function of the follicle-stimulating hormone (FSH) receptor, alterations in apoptosis control, mutations in Sal-like 4 genes, and thymulin or basonuclin-1 deficiency. The above mentioned may be good targets for gene therapy in order to correct defects leading to POI. The goal of this review is to summarize current experiences on POI studies that employed gene therapy, and to discuss possible future directions in this field. Full article
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