Ovarian tissue and oocyte cryopreservation prior to iatrogenic premature ovarian insufficiency

Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.

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Association between Serum Vitamin A Levels and Premature Ovarian Insufficiency Risk

10.21203/rs.3.rs-192703/v1 ◽

2021 ◽

Author(s):

Yang Song ◽

Peiqiong Chen ◽

Wenxian Xu ◽

Yizhou Huang ◽

Yingxian Jia ◽

...

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Lipid Level ◽

Ovarian Tissue ◽

Serum Vitamin ◽

Premature Ovarian Insufficiency ◽

Control Group ◽

Binary Logistic Regression Analysis ◽

Ovarian Insufficiency ◽

Negatively Associated

Abstract Purpose: The aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). Methods: In this cross-sectional survey, women with POI (n = 47) and normo-ovulatory controls (n = 67) were enrolled from December 2016 to May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of vitamin A levels with POI risk was assessed using binary logistic regression analysis. Results: Serum vitamin A levels seems slightly higher in the POI group than in the control group (728.00 ± 176.00 vs 503.93 ± 145.64 µg/L, p = 0.133). But after adjust with serum lipid level, serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs 157.56 ± 35.21 µg/mmol, p = 0.035). Further, serum vitamin A/TC ratio was significantly and negatively associated with POI risk [unadjusted odds ratio (OR) = 0.988, 95% confidence interval (CI): 0.977–0.999, p = 0.039]. The same trend was found after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972–0.999, p = 0.040). Conclusion: Serum vitamin A/TC ratio was negatively associated with POI risk, indicating that vitamin A deficiency may be a risk factor for POI development. Serum vitamin A/TC ratio may serve as a predictive factor for POI incidence. Thus, vitamin A may serve a protective role in ovarian tissue.

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iPSC-Derived Ovarian Tissue Restores Ovarian Function in Subfertile Mice and After Gonadotoxic Chemotherapy

10.1101/697532 ◽

2019 ◽

Author(s):

K.M. Elias ◽

N.W. Ng ◽

K.U. Dam ◽

A. Milne ◽

E.R. Disler ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Nude Mice ◽

Ovarian Tissue ◽

Stem Cell Differentiation ◽

Reproductive Hormones ◽

Reproductive Age ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Hormone Synthesis

AbstractMany reproductive age women with cancer who receive chemotherapy are exposed to gonadotoxic agents and risk diminished ovarian reserve, sterility, and premature menopause. Previously, we reported the derivation of steroidogenic ovarian cells from induced pluripotent and embryonic stem cells. Derived cells not only produced reproductive hormones, but also displayed markers of ovarian tissue and primordial gametes. Here, we describe that human follicular fluid (HFF), when added to our stem cell differentiation system, enhances the steroidogenic potential of differentiating stem cells and increases the subpopulation of cells that express the ovarian and germ cell markers GJA1 and ZP1, respectively. More importantly, using an in vivo model of chemotherapy-induced premature ovarian insufficiency in subfertile nude mice, we demonstrate that orthotopic implantation of these derived cells restores ovarian hormone synthesis and produces functional stem cell-derived oocytes. Additionally, these cells also ameliorate subfertility in nude mice, as demonstrated by the delivery of multiple litters of healthy pups from stem cell-derived oocytes. Collectively, these data support the hypothesis that stem cell-derived steroidogenic ovarian tissue could be used to promote neo-gametogenesis and treat the endocrinologic and reproductive sequelae of premature ovarian insufficiency.One Sentence SummaryWe show that orthotopic injection of sorted, differentiated iPSCs in ovaries of subfertile mice restores reproductive hormone synthesis and fertility.

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First pregnancy in China after ovarian tissue transplantation to prevent premature ovarian insufficiency

Climacteric ◽

10.1080/13697137.2021.1956453 ◽

2021 ◽

pp. 1-5

Author(s):

X. Ruan ◽

J. Du ◽

D. Lu ◽

W. Duan ◽

F. Jin ◽

...

Keyword(s):

Ovarian Tissue ◽

Tissue Transplantation ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Ovarian Tissue Transplantation

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CUMS Promotes the Development of Premature Ovarian Insufficiency Mediated by Nerve Growth Factor and Its Receptor in Rats

BioMed Research International ◽

10.1155/2020/1946853 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Xiaoyan Fu ◽

Qun Zheng ◽

Ning Zhang ◽

Mingxing Ding ◽

Xiaoming Pan ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Ovarian Function ◽

Ovarian Tissue ◽

Premature Ovarian Insufficiency ◽

Mild Stress ◽

Ovarian Insufficiency ◽

Female Population ◽

Nerve Growth

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF in vitro. Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH in vitro, and improve the rat ovarian function. Future studies may associate these results with female population.

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Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency

HORMONES ◽

10.1007/s42000-019-00134-4 ◽

2019 ◽

Vol 18 (4) ◽

pp. 409-415 ◽

Cited By ~ 2

Author(s):

Nikolaos Thanatsis ◽

Apostolos Kaponis ◽

Vasiliki Koika ◽

Neoklis A. Georgopoulos ◽

George O. Decavalas

Keyword(s):

Mrna Expression ◽

Ovarian Tissue ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Human Ovarian Tissue

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Association of Coenzyme Q10 with Premature Ovarian Insufficiency

10.21203/rs.3.rs-103183/v1 ◽

2020 ◽

Author(s):

Linjuan Ma ◽

Xiaojun Li ◽

Chunming Li ◽

Peiqiong Chen ◽

Yibing Lan ◽

...

Keyword(s):

Total Cholesterol ◽

Coenzyme Q10 ◽

Protective Factor ◽

Ovarian Tissue ◽

Premature Ovarian Insufficiency ◽

Annual Household Income ◽

Ovarian Insufficiency ◽

Cross Sectional ◽

Menstrual Cycles ◽

Cholesterol Ratio

Abstract ObjectiveThe aim of the study was to analyze the relationship between levels of coenzyme Q10 (CoQ10) and the risk of premature ovarian insufficiency (POI).MethodsIn this cross-sectional case-control study, 32 women with POI and 58 women with normal menstrual cycles were recruited. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), CoQ10 and total cholesterol were measured. The association of CoQ10 with POI was assessed using binary logistic regression analysis.ResultsThe CoQ10/total cholesterol ratio was significantly lower in the women with POI than in the women with normal menstrual cycles (120.94 ± 25.35 nmol/mmol vs 138.97 ± 39.19 nmol/mmol, P = 0.021). The serum CoQ10/total cholesterol ratio was inversely associated with POI (the unadjusted odds ratio (OR) = 0.984, 95% CI: 0.970 - 0.998, P = 0.027). The same trend was found after adjusting for confounding factors (such as age, body mass index, annual household income and education) (OR = 0.976, 95% CI: 0.956 - 0.996, P = 0.020).ConclusionsThe serum CoQ10/total cholesterol ratio was inversely associated with POI, indicating that antioxidant deficiency may be a risk associated with the development of POI. CoQ10 may be a protective factor for ovarian tissue.

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