A 19 years old patient with primary amenorrhea was referred to our center. Based on discrepancy between high follicle stimulating hormone (FSH) level and normal ovarian reserve parameters, follicle stimulating hormone...A 19 years old patient with primary amenorrhea was referred to our center. Based on discrepancy between high follicle stimulating hormone (FSH) level and normal ovarian reserve parameters, follicle stimulating hormone receptor (FSHR) mutation was screened. The patient was homozygous in exon 6 of the FSHR gene for the new variant c.479T > C and predicted to result in an aminoacid substitution p.Ile160Thr. One year later, her anti-müllerian hormone (AMH) level inexplicably decreased. Oocyte vitrification was thus offered for fertility preservation. After 17 days of recombinant follicle stimulating hormone (recFSH) (900 IU daily), no follicular growth was seen and estradiol levels remained low. In vitro maturation (IVM) was then suggested. Ten oocytes were successfully vitrified.展开更多
Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but...Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.展开更多
Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three pr...Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.展开更多
Background Primary ovarian insufficiency （POI） is defined as a primary ovarian defect characterized by absent menarche （primary amenorrhea） or premature depletion of ovarian follicles before the age of 40 years. T...Background Primary ovarian insufficiency （POI） is defined as a primary ovarian defect characterized by absent menarche （primary amenorrhea） or premature depletion of ovarian follicles before the age of 40 years. The etiology of primary ovarian insufficiency in human female patients is still unclear. The purpose of this study is to investigate the potential genetic causes in primary amenorrhea patients by high resolution array based comparative genomic hybridization （array-CGH） analysis. Methods Following the standard karyotyping analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15 normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays following the standard protocol. Copy number variations identified by array-CGH were confirmed by real time polymerase chain reaction.展开更多
Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms resu...Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms result from abnormal levels of sex hormones,especially estrogen.The most prevalent treatment is hormone replacement therapy(HRT),which can relieve symptoms and improve quality of life.However,HRT cannot restore ovarian functions,including secretion,ovulation,and fertility.Recently,as part of a developing field of regenerative medicine,stem cell therapy has been proposed for the treatment of POI.Thus,we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment,and sum up the underlying mechanisms of action.A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.展开更多
A matured oocyte has experienced three critical division stages: (1) proliferation in early fetal stage, (2) meiotic arrest at diplotene of prophase I, and (3) meiotic resumption and extrusion of the first polar body....A matured oocyte has experienced three critical division stages: (1) proliferation in early fetal stage, (2) meiotic arrest at diplotene of prophase I, and (3) meiotic resumption and extrusion of the first polar body. The abnormalities of these stages are associated closely with female reproduction problems including primary ovarian insufficiency (POI), the pathogenic mechanisms of which consist of insufficient initial follicle number, accelerated follicle loss, and arrest of follicle development. Recently, many meiotic associated genetic factors were identified to be mutated in POI patients and mouse models, revealing the association between meiosis and ovarian reserve. In this review, we provide an overview of the genetic factors involved in meiotic prophase I and their pathogenic mechanisms in POI.展开更多
Background: The aim of this study is to investigate the prevalence of the fragile X mental retardation 1(FMR1) gene premutation in Han Chinese women with primary ovarian insufficiency(POI) using a rapid and cost-effec...Background: The aim of this study is to investigate the prevalence of the fragile X mental retardation 1(FMR1) gene premutation in Han Chinese women with primary ovarian insufficiency(POI) using a rapid and cost-effective method. Methods: A total of 153 Han Chinese women with sporadic POI were systematically analyzed for trinucleotide repeats within the FMR1 gene. We employed an improved strategy to screen for cytosine-guanine-guanine repeats in the 5’ untranslated region of the FMR1 gene. Before using the previously reported Fragil Ease polymerase chain reaction(PCR) method for premutation identification, we developed a new cost-effective PCR-based method to exclude most of the normal allele carriers during the initial screening stage. Results: In our initial screening, 62.1% of women with POI were found to carry heterozygous normal alleles of FMR1, which were recognized by our sensitive and cost-effective method. The remaining women were further screened for the presence of the FMR1 premutation. We identified a Han Chinese woman with a premutation allele of FMR1 out of 153 sporadic POI women(0.7%). Conclusions: The frequent FMR1 premutation in Caucasian individuals with POI may not be a common genetic cause of sporadic POI in the Han Chinese population.展开更多
目的研究血清中25(OH)D水平对隐匿型原发性卵巢功能不全(occult primary ovarian insufficiency,oPOI)患者妊娠结局的影响。方法回顾性分析2018年9月至2022年12月在广东省妇幼保健院生殖中心行辅助生殖治疗的218例患者的临床资料。将符...目的研究血清中25(OH)D水平对隐匿型原发性卵巢功能不全(occult primary ovarian insufficiency,oPOI)患者妊娠结局的影响。方法回顾性分析2018年9月至2022年12月在广东省妇幼保健院生殖中心行辅助生殖治疗的218例患者的临床资料。将符合纳入标准的对照组和oPOI组患者按孕产妇的年龄节点分为≤35岁和>35岁,比较各组的25(OH)D浓度及妊娠结局的差异,随后对oPOI患者进行维生素D补充,追踪助孕结局。结果在≤35岁患者中,oPOI组的25(OH)D水平及妊娠率显著低于对照组(41.62±11.90 vs 63.04±16.26,42.37±4.62 vs 53.33±1.97,P<0.05),在>35岁患者中,25(OH)D水平及妊娠率均无显著性差异。在≤35岁oPOI患者中,25(OH)D干预组的血清25(OH)D浓度和优质胚胎率显著高于25(OH)D未干预组,差异具有统计学意义(42.13±12.91 vs 78.26±23.91,55.74±25.16 vs 80.39±29.05,P<0.05),但两组间的获卵数、受精率、临床妊娠率和着床率均没有显著差异;在>35岁的oPOI患者中,25(OH)D干预组与未干预组的血清25(OH)D浓度、获卵数、受精率、优质胚胎率、临床妊娠率和着床率均未见显著差异。结论≤35岁的女性不孕患者中,oPOI患者的维生素D水平低于其他因素不孕的患者,给予维生素D补充后可改善oPOI患者25(OH)D水平及优质胚胎率,但未改变oPOI患者的妊娠结局。展开更多
文摘A 19 years old patient with primary amenorrhea was referred to our center. Based on discrepancy between high follicle stimulating hormone (FSH) level and normal ovarian reserve parameters, follicle stimulating hormone receptor (FSHR) mutation was screened. The patient was homozygous in exon 6 of the FSHR gene for the new variant c.479T > C and predicted to result in an aminoacid substitution p.Ile160Thr. One year later, her anti-müllerian hormone (AMH) level inexplicably decreased. Oocyte vitrification was thus offered for fertility preservation. After 17 days of recombinant follicle stimulating hormone (recFSH) (900 IU daily), no follicular growth was seen and estradiol levels remained low. In vitro maturation (IVM) was then suggested. Ten oocytes were successfully vitrified.
基金This work was supported by the Science Fund of the Republic of Serbia(IDEAS),Project Number:7750154(NPATPETTMPCB).Project Title:New Prognostic and Theranostic Potential of Enzymes Involved in CoTranscriptional Cleavage and Co-Translational Modification in Prostate,Colorectal,and Breast Cancer Tissue.
文摘Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.
文摘Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.
文摘Background Primary ovarian insufficiency （POI） is defined as a primary ovarian defect characterized by absent menarche （primary amenorrhea） or premature depletion of ovarian follicles before the age of 40 years. The etiology of primary ovarian insufficiency in human female patients is still unclear. The purpose of this study is to investigate the potential genetic causes in primary amenorrhea patients by high resolution array based comparative genomic hybridization （array-CGH） analysis. Methods Following the standard karyotyping analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15 normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays following the standard protocol. Copy number variations identified by array-CGH were confirmed by real time polymerase chain reaction.
基金This work was supported by the Beijing Dongcheng Department of Science,Technology,and Information(BJ-2019-103 to Shaowei Wang).
文摘Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms result from abnormal levels of sex hormones,especially estrogen.The most prevalent treatment is hormone replacement therapy(HRT),which can relieve symptoms and improve quality of life.However,HRT cannot restore ovarian functions,including secretion,ovulation,and fertility.Recently,as part of a developing field of regenerative medicine,stem cell therapy has been proposed for the treatment of POI.Thus,we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment,and sum up the underlying mechanisms of action.A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.
基金This work was supported by funding from the National Key R&D Program of China(2016YFC1303100)。
文摘A matured oocyte has experienced three critical division stages: (1) proliferation in early fetal stage, (2) meiotic arrest at diplotene of prophase I, and (3) meiotic resumption and extrusion of the first polar body. The abnormalities of these stages are associated closely with female reproduction problems including primary ovarian insufficiency (POI), the pathogenic mechanisms of which consist of insufficient initial follicle number, accelerated follicle loss, and arrest of follicle development. Recently, many meiotic associated genetic factors were identified to be mutated in POI patients and mouse models, revealing the association between meiosis and ovarian reserve. In this review, we provide an overview of the genetic factors involved in meiotic prophase I and their pathogenic mechanisms in POI.
基金supported by the National Key Research and Development Program of China(2016YFC0905100)the National Natural Science Foundation of China(31625015,31521003,and 31571297).
文摘Background: The aim of this study is to investigate the prevalence of the fragile X mental retardation 1(FMR1) gene premutation in Han Chinese women with primary ovarian insufficiency(POI) using a rapid and cost-effective method. Methods: A total of 153 Han Chinese women with sporadic POI were systematically analyzed for trinucleotide repeats within the FMR1 gene. We employed an improved strategy to screen for cytosine-guanine-guanine repeats in the 5’ untranslated region of the FMR1 gene. Before using the previously reported Fragil Ease polymerase chain reaction(PCR) method for premutation identification, we developed a new cost-effective PCR-based method to exclude most of the normal allele carriers during the initial screening stage. Results: In our initial screening, 62.1% of women with POI were found to carry heterozygous normal alleles of FMR1, which were recognized by our sensitive and cost-effective method. The remaining women were further screened for the presence of the FMR1 premutation. We identified a Han Chinese woman with a premutation allele of FMR1 out of 153 sporadic POI women(0.7%). Conclusions: The frequent FMR1 premutation in Caucasian individuals with POI may not be a common genetic cause of sporadic POI in the Han Chinese population.
文摘目的研究血清中25(OH)D水平对隐匿型原发性卵巢功能不全(occult primary ovarian insufficiency,oPOI)患者妊娠结局的影响。方法回顾性分析2018年9月至2022年12月在广东省妇幼保健院生殖中心行辅助生殖治疗的218例患者的临床资料。将符合纳入标准的对照组和oPOI组患者按孕产妇的年龄节点分为≤35岁和>35岁,比较各组的25(OH)D浓度及妊娠结局的差异,随后对oPOI患者进行维生素D补充,追踪助孕结局。结果在≤35岁患者中,oPOI组的25(OH)D水平及妊娠率显著低于对照组(41.62±11.90 vs 63.04±16.26,42.37±4.62 vs 53.33±1.97,P<0.05),在>35岁患者中,25(OH)D水平及妊娠率均无显著性差异。在≤35岁oPOI患者中,25(OH)D干预组的血清25(OH)D浓度和优质胚胎率显著高于25(OH)D未干预组,差异具有统计学意义(42.13±12.91 vs 78.26±23.91,55.74±25.16 vs 80.39±29.05,P<0.05),但两组间的获卵数、受精率、临床妊娠率和着床率均没有显著差异;在>35岁的oPOI患者中,25(OH)D干预组与未干预组的血清25(OH)D浓度、获卵数、受精率、优质胚胎率、临床妊娠率和着床率均未见显著差异。结论≤35岁的女性不孕患者中,oPOI患者的维生素D水平低于其他因素不孕的患者,给予维生素D补充后可改善oPOI患者25(OH)D水平及优质胚胎率,但未改变oPOI患者的妊娠结局。
