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Orphanet Journal of Rare Diseases Aug 2020Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part... (Review)
Review
BACKGROUND
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX).
MAIN BODY
The diagnosis is often made during adolescence following investigations for primary amenorrhea and has an estimated prevalence of 1 in 5000 live female births. MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line therapy or by surgery. MRKH syndrome involves absolute uterine factor infertility and until recently, the only option for the patients to achieve biological motherhood was through gestational surrogacy, which is prohibited in most countries. However, the successful clinical trial of uterus transplantation (UTx) by a Swedish team followed by the first live-birth in September, 2014 in Gothenburg, proofed the first available fertility treatment in MRKH syndrome and UTx is now being performed in other countries around the world allowing women with MRKH syndrome to carry their own child and achieve biological motherhood.
CONCLUSION
Several advances in research across multiple disciplines have been made in the recent years and this kaleidoscopic review provides a current status of various key aspects in MRKH syndrome and provides perspectives for future research and improved clinical care.
Topics: 46, XX Disorders of Sex Development; Adolescent; Child; Congenital Abnormalities; Female; Humans; Mullerian Ducts; Uterus; Vagina
PubMed: 32819397
DOI: 10.1186/s13023-020-01491-9 -
Frontiers in Endocrinology 2020Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex.... (Review)
Review
Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex. In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Müllerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia. The process of sex differentiation can also be disrupted at the stage of genital differentiation, due to isolated defects in androgen or AMH secretion, but not both. These are forms of fetal-onset hypogonadism with dissociated gonadal dysfunction. In this review, we present a perspective on impaired testicular endocrine function, i.e., fetal-onset male hypogonadism, resulting in incomplete virilization at birth.
Topics: Disorders of Sex Development; Humans; Hypogonadism; Male
PubMed: 32351452
DOI: 10.3389/fendo.2020.00211 -
Revista Brasileira de Ginecologia E... Apr 2022Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging since normal pubertal development overlap typical features of this syndrome. The authors...
Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging since normal pubertal development overlap typical features of this syndrome. The authors aim to summarize the existing evidence concerning PCOS in adolescence, particularly its diagnostic criteria and therapeutic options. A search throughout medical databases such as PubMed and MedScape was performed. Diagnostic criteria include irregular menstrual cycles according to time postmenarche and evidence of clinical hyperandrogenism and/or biochemical hyperandrogenism, provided other causes have been excluded. Polycystic ovarian morphology ought not to be used as a diagnostic criterion. Treatment should target manifestations and/or comorbidities, even in the absence of a definite diagnosis. Lifestyle interventions are the first-line treatment. Combined oral contraceptives, metformin or antiandrogens may also be considered as adjuvants. Screening for PCOS in adolescence is crucial as it allows an early intervention on the symptoms and comorbidities presented leading to better long-term reproductive and metabolic outcomes.
Topics: Adolescent; Female; Humans; Hyperandrogenism; Life Style; Menstruation Disturbances; Metformin; Polycystic Ovary Syndrome
PubMed: 35623621
DOI: 10.1055/s-0042-1742292 -
Reviews in Endocrine & Metabolic... Feb 2023Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency caused by mutations in the CYP21A2 gene. Although women with CAH have decreased fecundity, they are able to conceive; thus, if pregnancy is not desired, contraception options should be offered. If fertility is desired, women with classic CAH should first optimize glucocorticoid treatment, followed by ovulation induction medications and gonadotropins if needed. Due to the possible pregnancy complications and implications on the offspring, preconception genetic testing and counseling with a high-risk obstetrics specialist is recommended. For couples trying to avoid having a child with CAH, care with a reproductive endocrinology and infertility specialist to utilize in vitro fertilization can be offered, with or without preimplantation genetic testing for monogenic disorders. Prenatal screening and diagnosis options during pregnancy include maternal serum cell free-DNA for sex of the baby, and chorionic villus sampling and amniocentesis for diagnosis of CAH. Pregnant women with classic CAH need glucocorticoids to be adjusted during the pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis. Maternal and fetal risks may include chorioamnionitis, maternal hypertension, gestational diabetes, cesarean section, and small for gestational age infants. This review on CAH due to 21-hydroxylase deficiency highlights reproductive health including genetic transmission, contraception options, glucocorticoid management, fertility treatments, as well as testing, antenatal monitoring, and management during pregnancy, delivery, and postpartum.
Topics: Child; Pregnancy; Female; Humans; Adrenal Hyperplasia, Congenital; Glucocorticoids; Cesarean Section; Postpartum Period; Steroid 21-Hydroxylase
PubMed: 36399318
DOI: 10.1007/s11154-022-09770-5 -
Taiwanese Journal of Obstetrics &... Sep 2020Fetal sex discordance is an entity that is becoming more frequent due to the expansion of the cfDNA for prenatal diagnosis. Its incidence can be estimated in 1/1500-2000... (Review)
Review
Fetal sex discordance is an entity that is becoming more frequent due to the expansion of the cfDNA for prenatal diagnosis. Its incidence can be estimated in 1/1500-2000 pregnancies, a frequency as high as that of some common chromosomopathies. The causes of this phenomenon are multiple and diverse, ranging from laboratory errors to important pathologies such as disorders of sexual differentiation. The management of a case of fetal sex discordance must be structured, starting with the review of the clinical history and the tests performed, and may require the performance of invasive tests to reach a diagnosis. Prevention through adequate pretest counseling and ultrasound confirmation can help to reduce its incidence.
Topics: Cell-Free Nucleic Acids; Disorders of Sex Development; Female; Humans; Maternal Serum Screening Tests; Pregnancy; Sex Characteristics; Sex Determination Analysis; Ultrasonography, Prenatal
PubMed: 32917312
DOI: 10.1016/j.tjog.2020.07.004 -
Tidsskrift For Den Norske Laegeforening... Nov 2019
Topics: Humans; Kallmann Syndrome
PubMed: 31746176
DOI: 10.4045/tidsskr.19.0370 -
Lakartidningen Oct 2019
Review
Topics: Adolescent; Age of Onset; Autism Spectrum Disorder; Child; Comorbidity; Disorders of Sex Development; Feeding and Eating Disorders; Gender Dysphoria; Humans; Interdisciplinary Communication; Legislation, Medical; Patient Care Team; Sex Reassignment Surgery; Sweden; Transsexualism; Young Adult
PubMed: 31613370
DOI: No ID Found -
Hormone Research in Paediatrics 2023Research and audit are vital for the management of Differences/Disorders of Sex Development (DSD). Clinical networks have a strong potential to drive these activities... (Review)
Review
BACKGROUND
Research and audit are vital for the management of Differences/Disorders of Sex Development (DSD). Clinical networks have a strong potential to drive these activities with the development of care standards including patient experience data and peer-observation of clinical care provision.
SUMMARY
Following the 2005 Consensus Workshop that stressed the need for the regular collection and sharing of data across geographical boundaries, the current I-DSD registry was initially launched in 2008. Over a decade later, this registry and its associated network play an increasingly important role in supporting research, training, and benchmarking of care and service. Patient registries can also facilitate the development of local circles of patients and parents with similar conditions who can support each other.
KEY MESSAGES
The case for participating in standardized data collection and exchange for DSD has now been made and should be standard practice in centres that care for people with DSD.
Topics: Humans; Disorders of Sex Development; Registries; Sexual Development; Parents
PubMed: 35390801
DOI: 10.1159/000524516 -
Endocrinology and Metabolism Clinics of... Mar 2021Evidence of clinical and/or biochemical androgen excess poses a unique differential in postmenopausal women. Some signs and symptoms of postmenopausal hyperandrogenism... (Review)
Review
Evidence of clinical and/or biochemical androgen excess poses a unique differential in postmenopausal women. Some signs and symptoms of postmenopausal hyperandrogenism can be normal and attributed to the natural aging process. However, the causes of androgen excess in this group include both nontumorous and tumorous causes. Treatment of androgen excess may improve both quality of life and long-term metabolic outcomes.
Topics: Female; Humans; Hyperandrogenism; Postmenopause; Quality of Life; Testosterone
PubMed: 33518189
DOI: 10.1016/j.ecl.2020.12.002 -
European Journal of Medical Genetics Sep 2020The term chimera has been borrowed from Greek mythology and has a long history of use in biology and genetics. A chimera is an organism whose cells are derived from two... (Review)
Review
The term chimera has been borrowed from Greek mythology and has a long history of use in biology and genetics. A chimera is an organism whose cells are derived from two or more zygotes. Recipients of tissue and organ transplants are artificial chimeras. This review concerns natural human chimeras. The first human chimera was reported in 1953. Natural chimeras can arise in various ways. Fetal and maternal cells can cross the placental barrier so that both mother and child may become microchimeras. Two zygotes can fuse together during an early embryonic stage to form a fusion chimera. Most chimeras remain undetected, especially if both zygotes are of the same genetic sex. Many are discovered accidently, for example, during a routine blood group test. Even sex-discordant chimeras can have a normal male or female phenotype. Only 28 of the 50 individuals with a 46,XX/46,XY karyotype were either true hermaphrodites or had ambiguous genitalia. Blood chimeras are formed by blood transfusion between dizygotic twins via the shared placenta and are more common than was once assumed. In marmoset monkey twins the exchange via the placenta is not limited to blood but can involve other tissues, including germ cells. To date there are no examples in humans of twin chimeras involving germ cells. If human chimeras are more common than hitherto thought there could be many medical, social, forensic, and legal implications. More multidisciplinary research is required for a better understanding of this fascinating subject.
Topics: Chromosome Disorders; Disorders of Sex Development; Humans; Karyotype; Mosaicism; Phenotype
PubMed: 32565253
DOI: 10.1016/j.ejmg.2020.103971