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    Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.
    Endocr Dev 2018 12;33:113-127. Epub 2018 Jun 12.
    Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Read More

    Fertility Preservation in Endocrine Disorders during Transition for Girls.
    Endocr Dev 2018 8;33:128-148. Epub 2018 Jun 8.
    Recent advances in fertility preservation (FP) techniques have led to a wide spread of indications. FP should now be discussed not only for young girls having to receive gonadotoxic treatments for cancer, but also for those with genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency. For premenarchal girls, ovarian tissue cryopreservation is still the only available technique. Read More

    MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series.
    J Assist Reprod Genet 2018 Jun 7. Epub 2018 Jun 7.
    Laboratoire Clement, Avenue d'Eylau, 75016, Paris, France.
    Purpose: To evaluate the possibility of correcting metabolic defects in gametes and embryos due to methylene tetra hydrofolate reductase (MTHFR) isoforms C677T and A1298C, by supplementation with 5-methyl THF instead of synthetic folic acid. In these couples, high doses of folic acid lead to UMFA (un-metabolized folic acid) syndrome.

    Methods: Thirty couples with fertility problems lasting for at least 4 years, such as recurrent fetal loss, premature ovarian insufficiency, or abnormal sperm parameters, with two thirds of them having failed assisted reproductive technology (ART) attempts were included in this program. Read More

    Reproductive Function and Outcomes in Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Review.
    J Clin Oncol 2018 Jun 6:JCO2017763441. Epub 2018 Jun 6.
    Wendy van Dorp, Erasmus University Medical Center, Rotterdam; Renee L. Mulder, Emma Children's Hospital and Academic Medical Center; Eline van Dulmen-den Broeder, VU University Medical Center, Amsterdam; Marry M. van den Heuvel-Eibrink, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands; Riccardo Haupt, Istituto Giannina Gaslini, Genoa, Italy; Richard A. Anderson and W. Hamish Wallace, University of Edinburgh; W. Hamish Wallace, Royal Hospital for Sick Children, Edinburgh, United Kingdom; H. Irene Su, University of California, San Diego, CA; Jeanette Falck Winther, Danish Cancer Society Research Center, Copenhagen, and Aarhus University, Aarhus, Denmark; Melissa M. Hudson, St Jude Children's Research Hospital, Memphis, TN; and Jennifer M. Levine, Weill Cornell Medicine, New York, NY.
    Some survivors of childhood, adolescent, and young adult cancer are at increased risk of gonadal dysfunction and adverse pregnancy outcomes. We reviewed currently available literature that evaluated reproductive function and pregnancy outcomes of female cancer survivors diagnosed before the age of 25 years. High-dose alkylating agent chemotherapy and abdominal/pelvic radiotherapy adversely affect gonadal function in a dose-related fashion, with older age at exposure conferring greater risk as a result of the age-related decline in ovarian reserve. Read More

    Premature ovarian insufficiency and early depletion of the ovarian reserve in the monogenic Mulibrey nanism disorder.
    Hum Reprod 2018 Jun 1. Epub 2018 Jun 1.
    Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 HUS, Helsinki, Finland.
    Study Question: What is the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gene?

    Summary Answer: The number of ovarian follicles is highly reduced already in infant and young MUL girls and the majority of them will have early depletion of follicles resulting in clinical and biochemical signs of POI.

    What Is Known Already: Both female and male patients with MUL show failure of sexual maturation, signs of hypogonadism and infertility.

    Study Design, Size, Duration: We studied the gonadal function, pubertal development and ovarian reserve in 33 MUL patients aged 5. Read More

    Mechanism of resveratrol in improving ovarian function in a rat model of premature ovarian insufficiency.
    J Obstet Gynaecol Res 2018 May 30. Epub 2018 May 30.
    Department of Obstetrics and Gynecology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
    Aim: To investigate the mechanism of resveratrol treatment in chemically induced premature ovarian insufficiency (POI) in rats.

    Methods: Five-week-old specific pathogen-free healthy Sprague-Dawley female rats (n = 90) were randomly divided into five groups (n = 18): low-dose resveratrol (group A), moderate-dose resveratrol (group B), high-dose resveratrol (group C), model control group (group D) and blank control group (group E). POI was induced in rats from the resveratrol-treated groups and the model control group according to observed indexes using a previously established model (oral administration of tripterygium wilfordii polyglycoside tablet 50 mg/kg/day for 14 days). Read More

    Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients, refusing oocyte donation: a retrospective cohort study.
    Gynecol Endocrinol 2018 May 30:1-6. Epub 2018 May 30.
    e Obstetrics and Gynecology Department , McGill University , Montreal , Canada.
    The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. Read More

    Orthopedic-orthodontic treatment of the patient with Turner's syndrome: Review of the literature and case report.
    Spec Care Dentist 2018 May 30. Epub 2018 May 30.
    Department of Odontostomatology and Surgery, University of Bari, Bari, Italy.
    Aims: Turner syndrome (TS) patients have phenotypical variable presentations and they are more susceptible to endocrine, auto-immune, and structural anomalies. Typical clinical characteristics are short stature and premature ovarian insufficiency. Patients with TS show a typical cranial-facial morphology with bi-maxillary bi-retrusion, high-arched palate, micrognathia, and class II malocclusion. Read More

    A novel mutation in KHDRBS1 in a patient affected by primary ovarian insufficiency.
    Clin Endocrinol (Oxf) 2018 May 28. Epub 2018 May 28.
    Center for Research in Genetics and Genomics (CIGGUR), School of Medicine and Health Sciences, GENIUROS Research Group, Universidad del Rosario, Bogotá, Colombia.

    [Effects of electroacupuncture at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency].
    Zhongguo Zhen Jiu 2018 May;38(5):5193-26
    Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
    Objective: To explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI).

    Methods: A total of 48 SD female rats with regular estrus were divided into a blank group (=8), a model group (=10), an EA group (=10), a binding group (=10) and a tamoxifen (TAM) group (=10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet. Read More

    Menopause Symptom Management in the United Kingdom.
    Nurs Clin North Am 2018 Jun 7;53(2):263-277. Epub 2018 Apr 7.
    Gynaecology, Guys and St Thomas NHS Foundation Trust, Mcnair Centre, Guys Hospital, Ground Floor Southwark Wing, London SE1 9RT, UK. Electronic address:
    Menopause is a complex time in a woman's life. It is an increasingly a midlife event, when health care professionals should be aiming to optimize a woman's health for the next 30 years or so. Nurses need to be able to give up-to-date information and evidence for all forms of treatment based on a background of complex and ever-changing research. Read More

    Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study.
    Pediatr Blood Cancer 2018 May 11:e27232. Epub 2018 May 11.
    Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
    Background: We reviewed the effect of ovarian transposition (OT) on ovarian function among long-term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.

    Procedure: Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Read More

    Case Report: Cerebral leukodystrophy and the gonadal endocrinopathy: a rare but real association.
    F1000Res 2018 7;7:158. Epub 2018 Feb 7.
    Khyber Teaching Hospital, 25000, Peshawar, Pakistan.
    A 30 year old married Pakistani woman presented in January 2018 with an eight month history of progressive left sided weakness, ataxia, spasticity, underdeveloped secondary sexual characteristics and primary infertility. She was the elder sister of a 19 year old bed bound woman who was diagnosed with vanishing white matter (VWM) disease 12 months previously. The MRI scan of the brain  demonstrated diffuse leukodystrophy and her hormonal assays were significant for premature ovarian insufficiency. Read More

    Presentation, progression, and predictors of ovarian insufficiency in classic galactosemia.
    J Inherit Metab Dis 2018 May 2. Epub 2018 May 2.
    Department of Human Genetics, Emory University School of Medicine, Rm. 325.2 Whitehead Bldg., 615 Michael St., Atlanta, GA, 30322, USA.
    Classic galactosemia (CG) is an inherited metabolic disorder that affects about 1 in 50,000 live births in the United States and many other countries. With the benefit of early detection by newborn screening and rapid dietary restriction of galactose, generally achieved by removing dairy from the diet, most affected infants are spared the acute and potentially lethal symptoms of disease. Despite early detection and life-long dietary intervention, however, most patients grow to experience a constellation of long-term complications that include premature ovarian insufficiency in the vast majority of girls and young women. Read More

    Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data.
    J Clin Oncol 2018 May 2:JCO2018780858. Epub 2018 May 2.
    Matteo Lambertini, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Halle C.F. Moore, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Robert C.F. Leonard, Imperial College, London; Richard A. Anderson, University of Edinburgh, Edinburgh; Douglas J.A. Adamson, Ninewells Hospital, Dundee; Gianfilippo Bertelli, Sussex Cancer Centre, Brighton, United Kingdom; Sibylle Loibl, Keyur Mehta, and Sabine Seiler, German Breast Group, Neu-Isenburg; Bernd Gerber, University Hospital Rostock, Rostock, Germany; Pamela Munster, University of California, San Francisco, San Francisco, CA; Marco Bruzzone, Francesca Poggio, Marcello Ceppi, and Lucia Del Mastro, Ospedale Policlinico San Martino; Francesca Poggio and Lucia Del Mastro, University of Genova, Genova; Luca Boni, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Joseph M. Unger, SWOG Statistical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; Susan Minton, Moffitt Cancer Center, Tampa, FL; Kathy S. Albain, Loyola University Chicago Stritch School of Medicine, Maywood, IL; Amy Cripps, Nexgen Oncology, Dallas, TX; and Ann H. Partridge, Dana-Farber Cancer Institute, Boston, MA.
    Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Read More

    Successful fertility following optimized perfusion and cryopreservation of whole ovary and allotransplantation in a premature ovarian insufficiency rat model.
    J Ovarian Res 2018 May 2;11(1):35. Epub 2018 May 2.
    Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
    Background: Fertility preservation by whole ovary cryopreservation and transplantation (WOCP&TP) with vascular anastomosis requires successful cryopreservation. In this study, we investigated the possibility of restoring ovarian function and natural fertility after WOCP&TP in a premature ovarian insufficiency (POI) rat model. The influence of cryopreservation on the offspring of rats following WOCP&TP was also explored. Read More

    Identification of variants in pleiotropic genes causing "isolated" premature ovarian insufficiency: implications for medical practice.
    Eur J Hum Genet 2018 Apr 30. Epub 2018 Apr 30.
    Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
    Next-generation sequencing (NGS) is increasingly being used in a clinical setting for the molecular diagnosis of patients with heterogeneous disorders, such as premature ovarian insufficiency (POI). We performed NGS of ~1000 candidate genes in four unrelated patients with POI. We discovered the genetic cause of "isolated" POI in two cases, both of which had causative variants in surprising genes. Read More

    Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency.
    Trends Endocrinol Metab 2018 Jun 26;29(6):400-419. Epub 2018 Apr 26.
    Medical Faculty, Univ. Paris Sud and Paris Saclay, Bicetre Hospital 94275, Le Kremlin Bicêtre, France. Electronic address:
    Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Read More

    Challenges of fertility preservation in leukemia patients.
    Minerva Ginecol 2018 Apr 24. Epub 2018 Apr 24.
    Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel -
    An ongoing increase in survival rates among young leukemia patients is accompanied by a growing attention to possible long-term complications such as chemotherapy induced ovarian insufficiency and infertility. Therefore, an important element of the management of these patients is fertility preservation, which is challenged by considerations specific for leukemia. Such considerations include prepuberty, poor medical condition on presentation and the need for urgent chemotherapy, all of which may preclude the use of conventional assisted reproductive technologies. Read More

    [Protective effects of electroacupuncture pretreatment on ovarian in rats with premature ovarian insufficiency].
    Zhongguo Zhen Jiu 2018 Apr;38(4):405-11
    Departmentof Acupuncture and Moxibustion, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing 100053, China.
    Objective: To explore the protective effect and possible mechanism of electroacupuncture (EA) pretreatment at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian in rats with premature ovarian insufficiency (POI).

    Methods: A total of 32 SD female rats with regular estrus were randomly divided into a blank group, a model group, an EA group and an immobilization group, 8 rats in each one. The rats in the model group, EA group and immobilization group were treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (160 mg/kg) for 15 days to establish the model. Read More

    Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age.
    Sci Rep 2018 Apr 25;8(1):6516. Epub 2018 Apr 25.
    Ovarian Biology Laboratory, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
    Dacarbazine is commonly administered for the treatment of cancers prevalent in reproductive age females. However, investigations of off-target effects of dacarbazine on the ovary are limited. We assessed the impact of dacarbazine on the ovarian reserve of primordial follicles, essential for fertility. Read More

    Biomechanics and mechanical signaling in the ovary: a systematic review.
    J Assist Reprod Genet 2018 Apr 24. Epub 2018 Apr 24.
    Howard W. and Georgeanna Seegar Jones Division of Reproductive Sciences and Women's Health Research, Baltimore, MD, USA.
    Purpose: Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Read More

    [FMR1 PREMUTATION CARRIERS - ARE THEY REALLY ASYMPTOMATIC?]
    Harefuah 2018 Apr;157(4):241-244
    The Child Development Center, Sheba Medical Center, Tel Hashomer.
    Introduction: Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP). Read More

    Discordance between serum anti-Müllerian hormone concentrations and antral follicle counts: not only technical issues.
    Hum Reprod 2018 Jun;33(6):1141-1148
    CHU Lille, Service de Gynécologie Endocrinienne et Médecine de la Reproduction, Hôpital Jeanne de Flandre, F-59037 Lille, France.
    Study Question: Do patient-specific features contribute to the differences between measured serum anti-Müllerian hormone (AMH) concentrations and AMH values expected from the corresponding antral follicle count (AFC)?

    Summary Answer: Patient-specific features contribute to the differences between measured AMH values and AMH values expected from the corresponding AFC (AMHp), potentially through their effect on follicular AMH production.

    What Is Known Already: Both patient counselling and patient management could be hampered by finding of disagreement between AFC and AMH if both are used for the prediction of ovarian response. The difference between measured AMH concentrations and AMH values expected according to the corresponding AFC cannot be entirely explained by the technical limitations of counting of antral follicles and analytical variability of the AMH assay used. Read More

    Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects.
    J Inherit Metab Dis 2018 Apr 18. Epub 2018 Apr 18.
    Department of Pediatrics and Department of Clinical Genetics, Maastricht University Medical Center+, P. Debeylaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
    Classic galactosemia is a rare inherited disorder of galactose metabolism. Primary ovarian insufficiency (POI) with subfertility affects > 80% of female patients and is an important concern for patients and their parents. Healthcare providers are often consulted for subfertility treatment possibilities. Read More

    Risk of transplanting malignant cells in cryopreserved ovarian tissue.
    Minerva Ginecol 2018 Apr 11. Epub 2018 Apr 11.
    Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
    Improvements in cancer treatments have increased the chances of survival of young cancer patients, but have given rise to other issues, like premature ovarian insufficiency and infertility. Preservation and subsequent restoration of ovarian function in these patients is now possible thanks to ovarian tissue cryopreservation and transplantation. However, safety concerns about the possible presence of cancerous cells in the tissue to be cryopreserved must be addressed. Read More

    Fertility preservation in women with ovarian endometriosis.
    Minerva Ginecol 2018 Apr 11. Epub 2018 Apr 11.
    Gynecology Department, Cliniques Universitaires Saint Luc, Brussels, Belgium.
    Endometriosis is a frequently encountered benign gynecological disease that may be responsible for infertility. Treatment of endometriosis-associated infertility has been investigated using both medical and surgical therapeutic modalities. Therapy has essentially three main objectives: (i) to preserve and improve fertility, (ii) to reduce pain, and (iii) to delay recurrence. Read More

    [Fragile X syndrome and FMR1-dependent diseases - clinical presentation, epidemiology and molecular background].
    Dev Period Med 2018 ;22(1):14-21
    Zakład Genetyki Medycznej, Instytut Matki i Dziecka, Warszawa, Polska.
    Fragile X syndrome (FXS) is the second most common inherited cause of intellectual disability (ID), after Down syndrome. The severity of ID in FXS patients varies and depends mainly on the patient's sex. Besides intellectual disorders, additional symptoms, such as psychomotor delay, a specific behavioral phenotype, or emotional problems are present in FXS patients. Read More

    Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update.
    J Clin Oncol 2018 Apr 5:JCO2018781914. Epub 2018 Apr 5.
    Kutluk Oktay and Hugh S. Taylor, Yale University School of Medicine, New Haven, CT; Brittany E. Harvey, American Society of Clinical Oncology, Alexandria, VA; Ann H. Partridge, Dana-Farber Cancer Institute, Boston, MA; Gwendolyn P. Quinn, New York University School of Medicine, New York, NY; Joyce Reinecke, Alliance for Fertility Preservation, Lafayette; Erica T. Wang, Cedars-Sinai Medical Center, Los Angeles, CA; W. Hamish Wallace, The Hospital for Sick Children, Edinburgh, United Kingdom; Alison W. Loren, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA.
    Purpose To provide current recommendations about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from January 2013 to March 2017 was completed using PubMed and the Cochrane Library. An Update Panel reviewed the identified publications. Read More

    In vitro maturation of oocytes from excised ovarian tissue in a patient with autoimmune ovarian insufficiency possibly associated with Epstein-Barr virus infection.
    Reprod Biol Endocrinol 2018 Apr 5;16(1):33. Epub 2018 Apr 5.
    Reproductive Unit, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Zaloska cesta 002, 1000, Ljubljana, SI, Slovenia.
    Background: Some reports show that it is possible to isolate immature oocytes from human ovarian tissue retrieved by a cortex biopsy or ovariectomy of non-stimulated ovaries and mature them in vitro. The mature oocytes can be vitrified and stored for in vitro fertilization, which, along with ovarian tissue cryopreservation, is mostly practiced in young cancer patients to preserve their fertility. There is much less data on this new approach in women with a natural ovarian insufficiency, which can be caused by different factors, including viral infection. Read More

    Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency.
    Fertil Steril 2018 Apr 28;109(4):594-600.e1. Epub 2018 Mar 28.
    Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
    Objective: To evaluate the association between estrogen (E) exposure and deficiency and cardiovascular disease (CVD) risk among women with primary ovarian insufficiency (POI).

    Design: Cross-sectional study conducted between 1996 and 2016.

    Setting: Tertiary referral centers. Read More

    Clinical implication of FMR1 intermediate alleles in a Spanish population.
    Clin Genet 2018 Jul;94(1):153-158
    Biochemistry and Molecular Genetics Department, Hospital Clinic, Barcelona, Spain.
    FMR1 premutation carriers (55-200 CGGs) are at risk of developing Fragile X-associated primary ovarian insufficiency as well as Fragile X-associated tremor/ataxia syndrome. FMR1 premutation alleles are also associated with a variety of disorders, including psychiatric, developmental, and neurological problems. However, there is a major concern regarding clinical implications of smaller CGG expansions known as intermediate alleles (IA) or gray zone alleles (45-54 CGG). Read More

    Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion.
    Fertil Steril 2018 May 22;109(5):908-918.e2. Epub 2018 Mar 22.
    IVI Foundation, Valencia, Spain; Reproductive Medicine Research Group, Valencia, Spain.
    Objective: To assess if infusion of human bone marrow-derived stem cells (BMDSCs) could promote follicle development in patients with impaired ovarian functions.

    Design: Experimental design.

    Setting: University research laboratories. Read More

    Current approaches for the treatment of premature ovarian failure with stem cell therapy.
    Biomed Pharmacother 2018 Jun 22;102:254-262. Epub 2018 Mar 22.
    Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:
    One of the common disorders found in women is premature ovarian failure (POF). Recently some studies have explained premature ovarian insufficiency (POI). The causes of it are unknown although various types of study have been done. Read More

    Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency.
    Hum Mol Genet 2018 Jun;27(11):1913-1926
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
    Primary ovarian insufficiency (POI) is characterized by amenorrhea and loss or dysfunction of ovarian follicles prior to the age of 40. POI has been associated with autosomal recessive mutations in genes involving hormonal signaling and folliculogenesis, however, the genetic etiology of POI most often remains unknown. Here we report MRPS22 homozygous missense variants c. Read More

    Service evaluation project - Are local recommendations for onward referral to a specialist menopause clinic required to translate guidelines into practice?
    Post Reprod Health 2018 Jan 1:2053369118762241. Epub 2018 Jan 1.
    iCASH Clinic, Cambridge, UK.
    Objective Referral audit - are local recommendations required to translate guideline to practice? Study design In total, 50 consecutive, anonymised referral letters reviewed during the initial consultation in a specialist menopause clinic; the reasons for referral along with the patient's age and the source of referral were analysed. Results Several common reasons for referral were identified. Sexual dysfunction, including loss of libido and dyspareunia, resulted in 11 (22%) referrals. Read More

    Fertility and infertility: Definition and epidemiology.
    Clin Biochem 2018 Mar 16. Epub 2018 Mar 16.
    Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium. Electronic address:
    Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Males are found to be solely responsible for 20-30% of infertility cases but contribute to 50% of cases overall. Read More

    With low ovarian reserve, Highly Individualized Egg Retrieval (HIER) improves IVF results by avoiding premature luteinization.
    J Ovarian Res 2018 Mar 16;11(1):23. Epub 2018 Mar 16.
    The Center for Human Reproduction, New York, NY, 10021, USA.
    Background: Highly Individualized Egg Retrieval (HIER), defined as age-specific early oocyte retrieval (ER), has been demonstrated to avoid premature luteinization in women ≥43. We here investigated whether HIER also applies to younger women with premature ovarian aging (POA), and what best lead follicle size should be for administration of ovulation-triggers.

    Methods: Fifty-six women ≥43, and 37 POA patients underwent IVF cycles. Read More

    Molecular Aspects and Clinical Relevance of GDF9 and BMP15 in Ovarian Function.
    Vitam Horm 2018 ;107:317-348
    University of California San Diego, School of Medicine, La Jolla, CA, United States. Electronic address:
    Growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors with a leading role in the control of ovarian function in female reproduction, modulating both the cell fate of the somatic granulosa cells and the quality and developmental competence of the egg. This short review aims to consolidate the molecular aspects of GDF9 and BMP15 and their integral actions in female fertility to understand particularly their effects on oocyte quality and fetal growth. The significant consequences of mutations in the GDF9 and BMP15 genes in women with dizygotic twins as well as the clinical relevance of these oocyte factors in the pathogenesis of primary ovarian insufficiency and polycystic ovary syndrome are also addressed. Read More

    22q11.2 rearrangements found in women with low ovarian reserve and premature ovarian insufficiency.
    J Hum Genet 2018 May 14;63(5):691-698. Epub 2018 Mar 14.
    INSERM U1085-IRSET, Université de Rennes1, F-35042, Rennes, France.
    Ovarian reserve represents the number of available follicles/oocytes within ovaries and it can be assessed by follicle stimulating hormone levels, anti-Müllerian hormone levels, and/or antral follicle count determined by ultrasounds. A low ovarian reserve is defined by an abnormal ovarian reserve test. This condition can be considered premature if it occurs before the age of 40, leading to premature ovarian insufficiency. Read More

    A randomized, double-blind, placebo-controlled trial of Chinese herbal medicine capsules for the treatment of premature ovarian insufficiency.
    Menopause 2018 Mar 12. Epub 2018 Mar 12.
    Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
    Objective: This study was conducted to evaluate the treatment effectiveness of Chinese herbal medicine capsules containing the Yangyin Shugan formula (YYSG) in premature ovarian insufficiency (POI).

    Methods: One-hundred forty-six women with POI participated in this stratified, randomized, double-blind, placebo-controlled clinical trial. Participants in two groups (n = 73 in each)-the YYSG group and control group-underwent treatment for 12 weeks. Read More

    [Diffuse hypertrichosis revealing non-classical congenital adrenal hyperplasia].
    Ann Dermatol Venereol 2018 Apr 7;145(4):270-277. Epub 2018 Mar 7.
    Service de dermatologie, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex, France. Electronic address:
    Background: Non-classical congenital adrenal hyperplasia (NC-CAH) is a recessive autosomal disease caused by a deficiency of adrenal steroidogenesis enzymes. It must be distinguished from classical CAH, either simple virilising or salt-wasting, diagnosed during the neonatal period and responsible for potentially lethal disorders of sexual differentiation. NC-CAH presents a simpler and less specific clinical picture. Read More

    The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency.
    J Assist Reprod Genet 2018 May 9;35(5):857-862. Epub 2018 Mar 9.
    Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
    Purpose: To evaluate the effect of 12-month DHEA supplementation on menstrual pattern and ovarian reserve markers in women with premature ovarian insufficiency (POI) METHODS: This is a prospective observational study. Women with POI were given DHEA supplements (25 mg three times daily) for 12 months. Sonographic assessment for ovarian volume and antral follicle count (AFC) and serum measurement for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol, testosterone, liver function, and hemoglobin level were performed at baseline and monthly for 13 months after the supplementation. Read More

    Luteal Coasting and Individualization of Human Chorionic Gonadotropin Dose after Gonadotropin-Releasing Hormone Agonist Triggering for Final Oocyte Maturation-A Retrospective Proof-of-Concept Study.
    Front Endocrinol (Lausanne) 2018 15;9:33. Epub 2018 Feb 15.
    IVF Department, IVI Middle-East Fertility Clinic, Abu Dhabi, United Arab Emirates.
    Ovarian stimulation in a gonadotropin-releasing hormone (GnRH) antagonist protocol with the use of GnRH agonist for final oocyte maturation is the state-of-the-art treatment in patients with an expected or known high response to avoid or at least reduce significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Due to a shortened LH surge after administration of GnRH agonist in most patients, the luteal phase will be characterized by luteolysis and luteal phase insufficiency. Maintaining a sufficient luteal phase is crucial for achievement of a pregnancy; however, the optimal approach is still under debate. Read More

    Influence of Sexual Function on the Social Relations and Quality of Life of Women with Premature Ovarian Insufficiency.
    Rev Bras Ginecol Obstet 2018 Feb 28;40(2):66-71. Epub 2018 Feb 28.
    Department of Obstetrics and Gynecology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas, São Paulo, Brazil.
    Objective:  To evaluate the impact of sexual function (SF) in the quality of life (QoL) of women with premature ovarian insufficiency (POI).

    Methods:  Case-control study in which 80 women with POI were evaluated using estrogen plus progestogen therapy, compared with 80 women matched by age (±2 years) and presenting preserved gonadal function. Sexual function was evaluated using the Female Sexual Function Index (FSFI), and the QoL was evaluated using the World Health Organization's (WHO) QoL assessment instrument (WHOQoL-BREF). Read More

    Effects of oral contraceptives on ovulation induction in in vitro fertilization patients with premature ovarian insufficiency.
    Climacteric 2018 Jun 28;21(3):276-279. Epub 2018 Feb 28.
    a Navy Clinical Medical School , Anhui Medical University , Hefei , China.
    Objective: To report a case series of in vitro fertilization patients with premature ovarian insufficiency, who were treated with oral contraceptives to reduce follicle stimulating hormone levels.

    Method: This was a consecutive case series in a tertiary teaching hospital in China. Twenty-two women with refractory and idiopathic premature ovarian insufficiency were administered a drospirenone/ethinylestradiol oral contraceptive orally. Read More

    Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63.
    Nat Struct Mol Biol 2018 Mar 26;25(3):261-269. Epub 2018 Feb 26.
    Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance and Cluster of Excellence Macromolecular Complexes (CEF), Goethe University, Frankfurt, Germany.
    The survival rate of cancer patients is steadily increasing, owing to more efficient therapies. Understanding the molecular mechanisms of chemotherapy-induced premature ovarian insufficiency (POI) could identify targets for prevention of POI. Loss of the primordial follicle reserve is the most important cause of POI, with the p53 family member p63 being responsible for DNA-damage-induced apoptosis of resting oocytes. Read More

    FOXL2C134W-Induced CYP19 Expression via Cooperation With SMAD3 in HGrC1 Cells.
    Endocrinology 2018 Apr;159(4):1690-1703
    Department of Reproductive Medicine, School of Medicine, University of California, San Diego, La Jolla, California.
    Germline knockout studies in female mice demonstrated an essential role for forkhead box L2 (FOXL2) in early follicle development, whereas an inducible granulosa cell (GC)-specific deletion of Foxl2 in adults has shown ovary-to-testis somatic sex reprogramming. In women, over 120 different germline mutations in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus inversus syndrome associated with or without primary ovarian insufficiency. By contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult-type GC tumors (aGCTs). Read More

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