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      Questions concerning fertility preservation during transition in girls with Turner syndrome: review of the literature

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          Abstract

          Loss of fertility is one of the most important concerns facing Turner syndrome (TS) patients as they transition into adult health care. Due to the limited and rapidly decreasing ovarian reserve, many TS patients require fertility preservation (FP) techniques to preserve their reproductive potential until they are ready to pursue procreation. One has to also remember about the additional risks connected with pregnancy in TS patients. In order to determine the optimal time for introducing FP techniques and decrease the chance of an unnecessary intervention, markers and procedures assessing ovarian reserve have been developed. The exposure to potential cardiovascular complications should be determined before FP to avoid unnecessary procedures in patients with potential contraindications to pregnancy. The aim of the present review is to answer the following three questions important for successful preservation of fertility and safe pregnancy in TS: which markers of ovarian reserve should be used as selection criteria for FP? Which methods of FP are the safest and most effective? Are there any cardiovascular contraindications to FP? For each of those questions, separate literature searches have been conducted. A total of 86 articles have been included in this review: 34 for the first question, 35 for the second, and 17 for the third. Ovarian reserve markers and cardiovascular contraindications to pregnancy should be established before FP; hoverer, there are no unambiguous indicators as to which patients should be disqualified from the FP and more evidence is needed in this subject.

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          Most cited references91

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          Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

          Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting.
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            Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients.

            In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls. The objective of the study was to provide a reference range for AMH in girls and adolescents and to evaluate AMH as a marker of ovarian function. The study was conducted at a tertiary referral center for pediatric endocrinology. We measured AMH in 926 healthy females (longitudinal values during infancy) as well as in 172 Turner syndrome (TS) patients according to age, karyotype (A: 45,X; B: miscellaneous karyotypes; C: 45,X/46,XX), and ovarian function (1: absent puberty; 2: cessation of ovarian function; 3: ongoing ovarian function). AMH was undetectable in 54% (38 of 71) of cord blood samples (<2; <2-15 pmol/liter) (median; 2.5th to 97.5th percentile) and increased in all (37 of 37) infants from birth to 3 months (15; 4.5-29.5 pmol/liter). From 8 to 25 yr, AMH levels were stable (19.9; 4.7-60.1 pmol/liter), with the lower level of the reference range clearly above the detection limit. AMH levels were associated with TS-karyotype groups (median A vs. B: <2 vs. 3 pmol/liter, P = 0.044; B vs. C: 3 vs. 16 pmol/liter, P < 0.001) as well as with ovarian function (absent puberty vs. cessation of ovarian function: <2 vs. 6 pmol/liter, P = 0.004; cessation of ovarian function vs. ongoing ovarian function: 6 vs. 14 pmol/liter, P = 0.001). As a screening test of premature ovarian failure in TS, the sensitivity and specificity of AMH less than 8 pmol/liter was 96 and 86%, respectively. AMH seems to be a promising marker of ovarian function in healthy girls and TS patients.
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              Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome.

              Our aim was to study prevalence, incidence, age at diagnosis, and mortality in Turner syndrome (TS) in Denmark. Using the Danish Cytogenetic Register, we identified all cases (n = 781) of TS alive in Denmark during 1970-2001. Sixty-nine deceased women with TS were identified in the Causes of Death Register. We divided the cohort into women having the karyotype 45,X, karyotypes including an isochromosome Xq, and all other karyotypes associated with TS. We describe the number of patients diagnosed in Denmark yearly, incidence rates, and the age at diagnosis. Standardized mortality ratios (SMR) were calculated. A total of 349 women had a 45,X karyotype, 86 had a karyotype including an isochromosome Xq (isoXq), and 346 had another TS karyotype. Mortality was increased in TS with an SMR of 2.86 (95% confidence interval, 2.18-3.55). SMR was increased for coronary diseases, congenital malformations, endocrine diseases, and other causes. The mortality was increased for all types of karyotypes in comparison with the general population but was highest among females with 45,X and isoXq. There was a steady increase in prevalence, but incidence was unchanged. Age at diagnosis was mainly distributed in three periods: less than 1 yr of age (14.9%), during adolescence (10-17 yr) (33.2%), and during adulthood (38.5%), with a median age at diagnosis of 15.1 yr, decreasing during the study period (P < 0.01). Patients with TS and especially the karyotypes 45,X and isoXq have a higher mortality compared with the background population. TS was diagnosed with a considerable diagnostic delay. Prevalence is increasing, but incidence of TS was stable.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                03 October 2022
                01 December 2022
                : 11
                : 12
                : e220344
                Affiliations
                [1 ]Department of Pediatrics and Pediatric Endocrinology , Faculty of Medical Sciences, Medical University of Silesia, Katowice, Poland
                [2 ]Student Scientific Society at the Department of Pathophysiology , Jagiellonian University Medical College, Krakow, Poland
                Author notes
                Correspondence should be addressed to A Gawlik: agawlik@ 123456sum.edu.pl
                Author information
                http://orcid.org/0000-0002-9322-5502
                http://orcid.org/0000-0002-9309-4741
                Article
                EC-22-0344
                10.1530/EC-22-0344
                9641775
                36191160
                19b05cf9-1000-4818-af4d-5f2f2c07d66a
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 26 September 2022
                : 03 October 2022
                Categories
                Review

                turner syndrome,fertility preservation,ovarian reserve,cardiovascular risk

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