Pregnancy In Turner Syndrome Research Articles

P-676 Obstetric and perinatal outcomes in women with Turner Syndrome: A systematic review and meta-analysis

Abstract Study question What is the pooled risk of adverse obstetric and neonatal outcomes in pregnancies in women with Turner Syndrome (TS)? Summary answer TS women experience high rates of adverse outcomes. Risks are increased in egg donation pregnancies and multiple pregnancies compared to singleton spontaneous pregnancies. What is known already TS affects 1 in 2,000 live female births. The 2017 ‘Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome’ acknowledges women with TS are at increased risk of adverse obstetric and perinatal outcomes. Several retrospective cohort studies reporting obstetric and neonatal outcomes in TS pregnancies have been published in recent years. However, these studies are often limited to a single centre cohort, within one country and thus increasing risk of bias. Overall pooled risk estimates for each outcome have yet to be reported. Study design, size, duration A prospectively registered systematic review and meta-analysis was conducted and reported in line with PRISMA guidelines. Overall pooled rates of each outcome Is reported with 95% confidence interval. Pooled risk ratios comparing spontaneous and egg donation pregnancies are also reported. A comparative meta-analysis reports on dichotomous outcomes using summary risk ratio (RR) with 95%CI and on continuous outcomes using weighted mean difference (WMD) with 95%CI. Publication bias was assessed using the Newcastle-Ottawa Scale. Participants/materials, setting, methods A comprehensive literature search was undertaken. Eligibility screening was conducted by 2 independent reviewers. Studies were limited to English language with no time limit. Case reports were excluded. 30 studies reporting obstetric or perinatal outcomes in pregnancies of women with TS were included in the analysis. Outcome data was extracted and tabulated using a standard proforma. Main results and the role of chance 1724 pregnancies were included. Pooled risks: Obstetric outcomes: caesarean section (62.8%)(95%CI:57-76%), pregnancy-associated hypertensive disorders (21%)(95%CI:13-29%), pre-eclampsia (10%)(95%CI:6-14%),gestational diabetes mellitus (6.0%)(95%CI:4-8%), aortic dissection (1.1%)(95%CI:0-2%), intrahepatic cholestasis of pregnancy (4.6%)(95%CI:0-7%), post-partum haemorrhage (17.9%)(95%CI:-3-37%), and maternal mortality (0.3%)(95%CI:0-1%). Perinatal outcomes: prematurity (14.1%)(95%CI:8-18%), low birthweight (25.1%)(95%CI:12-23%), and perinatal mortality (1.2%)(95%CI:0-1%). Egg-donation pregnancies yield significantly higher rates of: caesarean section (82.8% vs. 55.7%) (RR1.49) (95% CI:1.27-1.76), pregnancy-associated hypertensive disorder (33.0% vs 12.9%: p=0.001), pre-eclampsia (16.9% vs 8.2%: p=0.0023), gestational hypertension (17.9% vs 0.0%: p=0.082), low-birthweight (43.0% vs 1.9%: p<0.001) and preterm birth (17.5% vs 0.0%: p<0.001) than spontaneous pregnancies. Multiple pregnancies resulted in high rates of prematurity (70.0%), low birth-weight (73.3%) and pregnancy-associated hypertensive disorders (60.9%). Limitations, reasons for caution Most studies were retrospective and included cases from many years ago so may not be reflective of current obstetric practice and improved care. Most studies were geographically clustered in Europe and North America. Estimations of risk may therefore not be generalisable to other ethnicities and middle and lower income countries Wider implications of the findings This study quantifies the risk of adverse outcomes in pregnancies in women with TS. Risk is increased further in egg donation pregnancies and strategies should aim to screen and prevent complications, particularly hypertensive disorders of pregnancy. Multiple pregnancy should be avoided through use of single embryo transfer. Trial registration number N/a

Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex

Turner syndrome (TS) leads to a characteristic phenotype, including premature ovarian insufficiency and infertility. Ovarian tissue cryopreservation (OTC) is becoming an established fertility preservation strategy for both pre- and post-pubertal females and may offer the chance of having a biological family to selected patients with TS. To date, women with TS have had ovarian tissue cryopreserved but there are few reports of autologous re-implantation and none of pregnancy. We herein report, to our knowledge, the first clinical pregnancy in a patient with TS, conceived naturally following re-implantation of cryopreserved ovarian tissue which had been removed soon after spontaneous puberty. This provides proof of concept for OTC as a means of fertility preservation in TS.

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

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.

Influence of Pregnancy on Aortic Diameter in Women With the Turner Syndrome

Women with Turner syndrome (TS) have high prevalence of cardiovascular anomalies. Literature suggests pregnancy is associated with a higher dissection risk, presumably preceded by aortic dilatation. Whether the aortic diameter truly changes during pregnancy in TS is not well investigated. This study aims to evaluate ascending aortic diameter change during pregnancy and reports on cardiac events during and directly after pregnancy. This tertiary hospital retrospective study investigated all TS women pregnancies (2009 to 2018). Outcome parameters included aortic diameter growth and aortic complications, specifically dissection. Thirty-five pregnancies in 30 TS women, 57% assisted by oocyte donation. Mean age at delivery 32 ± 5 years. In 27 pregnancies of 22 women imaging was available. From over 350 childless TS women a comparison group of 27 was individually matched. The median ascending aortic diameter growth between pre- and postpregnancy imaging was 1.0 mm (IQR -1.0; 2.0), no significant change (p = 0.077). Whether the patient had a bicuspid aortic valve (p = 0.571), monosomy X or mosaic karyotype (p = 0.071) or spontaneous pregnancy or resulting from oocyte donation (p = 0.686) had no significant influence on diameter change. Aortic growth between pregnancy and matched childless group (0.23 vs 0.32 mm/year, p = 0.788) was not significant over 3.3 ± 2 versus 4.4 ± 1 years. During pregnancy or the first 6 months after delivery no aortic complications were observed. In conclusion, this study suggests pregnancy in TS women does not induce faster ascending aortic diameter increase. Also not in presence of a bicuspid aortic valve, monosomy X karyotype, and oocyte donation. No aortic complications occurred. Based on current study pregnancy in TS women seems safe.

Cardiovascular outcomes of pregnancy in Turner syndrome

ObjectivesWomen with Turner syndrome (TS) are frequently counselled against pregnancy due to lack of data and unclear aortic dissection risk. However, with advances in fertility therapy, more women with TS...

Reproductive Life Course Project: Preliminary data from UK Turner Syndrome Pregnancy audit

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Non-cardiac maternal and fetal outcomes in Turner Syndrome pregnancies.

Non-cardiac maternal and fetal outcomes in Turner Syndrome pregnancies.

Fertility and Pregnancy in Turner Syndrome.

Turner syndrome (TS) occurs in one in 2500 live female births and is one of the most common chromosomal abnormalities in women. Pregnancies in women with TS, conceived with either autologous or donated oocytes, are considered high risk because of the associated miscarriages and life-threatening cardiovascular complications (aortic dissection, severe hypertension). Therefore, it is imperative to conduct a full preconception evaluation and counselling that includes cardiac assessment with Holter blood pressure monitoring, echocardiography, and thoracic MRI. Abnormal findings, such an aortic dilatation, mandate close monitoring throughout the pregnancy and the immediate postpartum period and could possibly contraindicate pregnancy. When invitro fertilization using donated oocytes is performed in these women, only a single embryo should be transferred. Women with a Turner mosaic karyotype appear to have a lower risk of obstetrical and cardiovascular complications but should nevertheless undergo the full preconception evaluation. In this article, we offer guidelines on the management of women with TS in the preconception period, during pregnancy, and postpartum.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death.

Reproductive and obstetric outcomes in mosaic Turner's Syndrome: a cross-sectional study and review of the literature.

BackgroundTurner’s syndrome (TS) is depicted as a total or partial absence of one X chromosome that results in ovarian dysgenesis. Chances of spontaneous pregnancy in TS are rare and the outcome of the pregnancies is known to be poor with an increased risk of miscarriage and stillbirths. Our aim is to evaluate reproductive and obstetric outcomes of natural conception and in-vitro fertilization (IVF) cycles in mosaic TS patients.MethodsA total of 22 mosaic TS cases (seventeen 45,X/46,XX and five 45,X/46,XX/47,XXX karyotypes) were evaluated.ResultsLive birth and abortion rates were found as 32.7 % and 67.3 %, respectively in 52 pregnancies. Implantation, clinical pregnancy and take home baby rates were detected as 3.7 %, 8.6 % and 5.7 %, respectively per IVF cycle as a result of 35 cycles. Fecundability analysis revealed that 5 % of the cases experienced first pregnancy within 6 months and 8 % within the first 2 years. Mosaicism ratio did not have an effect on the time to the first pregnancy (p = .149).ConclusionOnly a small proportion of the mosaic TS patients conceive in the first 2 years of the marriage. Age of menarche and age of marriage appear not to have any impact on the chance of conceiving. Mosaic TS cases should counseled about the low odds of pregnancy and high miscarriage rates.

Outcome of Spontaneous Pregnancy in Turner Syndrome

Outcome of Spontaneous Pregnancy in Turner Syndrome

Aortic dilatation and dissection in Turner syndrome: what we know, what we are unclear about and what we should do in clinical practice?

Aortic dilatation and aortic dissection are increasingly recognised in patients with Turner syndrome (TS). Risk factors for aortic dissection include aortic dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk of death due to aortic dissection in pregnancy in TS is 2%, which is approximately 100 times higher than the general population, as maternal mortality is extremely low. Ongoing cardiovascular monitoring is recommended, although there remain several unanswered questions in relation to cardiovascular imaging especially the choice of modality for detection of vascular, valvular abnormalities and measurements of aortic dimensions. Due to the relative short stature of patients with TS, aortic dimensions need to be defined by aortic measurements adjusted for body surface area, known as aortic sized index (ASI). The relationship of ASI and other risk factors with aortic dissection is only beginning to be clarified. Clinical management and monitoring of such patients should be delivered by a group of clinicians familiar with the issues unique to TS patients in a multidisciplinary fashion. All clinicians including the non-specialists need to have a low threshold of suspecting aortic dissection in these adolescents and young adults. This up to date review, including a summary of all 122 published cases of TS patients with aortic dissection, aims to provide a summary of recent publications on characteristics of aortic dissection and aortic dilatation in TS to highlight gaps in knowledge and propose possible clinical monitoring pathway of cardiovascular health in children and adults with TS. Cardiovascular assessment and risk counselling is especially crucial during the period of transition of adolescents with TS, although life long monitoring by expert cognizant to the issues specific in TS is essential.

Risks of pregnancy for women with Turner syndrome

Spontaneous pregnancy is rare among women with Turner syndrome (TS) since primary ovarian failure occurs in childhood for most patients. Recently, assisted pregnancies with donated oocytes have been successful in terms of live births among women with TS, but dire maternal cardiovascular complications have been reported. This article analyzes published data on TS pregnancies from 1960 to 2010 in order to identify specific risk factors predicting complications, including spontaneous versus assisted conception, pre-existing hypertension and abnormalities of the aortic valve or arch. Based on published case reports, the overall risk for major pregnancy complications in TS women is approximately 10% and the risk of maternal death is approximately 3.5%. The major risk factor for maternal death is an underlying aortic arch or aortic valve abnormality, which in most cases is not detected prior to pregnancy, due to absent or inadequate cardiovascular screening.

Women who gave birth to girls with Turner syndrome: maternal and neonatal characteristics

The aim was to identify maternal risk factors in women giving birth to girls with Turner syndrome (TS) and to describe the characteristics of newborns with TS. The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register. Between 1973 and 2005, 494 children with TS were born. Maternal age, parity, height, smoking habits and neonatal characteristics; mode of delivery, gestational age, size at birth and Apgar score, were compared with women in the general population who gave birth to girls during the same period. More women with advanced maternal age (40+) delivered girls with TS, 3.2% when compared with 1.8% in the general population [OR 1.83, 95% confidence interval (CI) 1.09-3.08, after adjustment for year of birth]. Maternal height was inversely associated with TS pregnancies (P = 0.005). Late preterm birth occurred in newborns with TS in 10.5% when compared with 4.8% in the general population (OR 2.23; 95% CI: 1.67-2.97, after adjustment for year of birth and maternal age). Newborns with TS had birthweight less than -2SD in 17.8% and birth length less than -2SD in 21.0% when compared with 3.5 and 3.4%, in the general population (OR 6.55; 95% CI: 5.12-8.38 and OR 8.69; 95% CI: 6.89-10.97, after adjustment for year of birth and maternal age). Advanced maternal age and short stature were risk factors for giving birth to a girl with TS. More TS girls were born late preterm and were smaller for gestational age than non-TS girls in the general population.

Multiple-marker screening in pregnancies with hydropic and nonhydropic Turner syndrome

OBJECTIVE: The combination of maternal serum αfetoprotein, unconjugated estriol, and human chorionic gonadotropin levels and maternal age has been used to increase the sensitivity of screening for fetal Down syndrome and trisomy 18 in early-second-trimester pregnancies. We hypothesized that a unique pattern of these analytes also may be characteristic of fetal Turner syndrome, with or without hydrops. STUDY DESIGN: We studied preamniocentesis, second-trimester maternal serum specimens from seven hydropic and eight nonhydropic cases of fetal Turner syndrome. Clinical and pathologic records were reviewed. Statistical analysis of the data was performed by the rank sum test. RESULTS: In both hydropic and nonhydropic cases, α-fetoprotein levels were slightly reduced, and unconjugated estriol levels were markedly reduced. In hydropic pregnancies human chorionic gonadotropin levels were elevated, and nonhydropic pregnancies had low human chorionic gonadotropin levels ( p = 0.001). CONCLUSIONS: The results suggest that the morphologic defect of hydrops, rather than the aneuploidy itself, is responsible for the elevation in human chorionic gonadotropin. In conjunction with the low unconjugated estriol levels, the elevation in human chorionic gonadotropin levels will result in the prenatal identification of hydropic fetal Turner syndrome pregnancies as being at increased risk for fetal Down syndrome. ( Am J Obstet Gynecol 1992;167:1021–4.)