Obstetric outcomes in women with Turner karyotype.

CONTEXT: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. OBJECTIVE: This study compared obstetric outcome in women with TS karyotype with women in the general population. DESIGN: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. RESULTS: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. CONCLUSIONS: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Psychological well-being in women with Turner syndrome: somatic and social correlates.

Our aim was to examine possible somatic and social correlates to psychological well-being in adult women with Turner Syndrome (TS), including hormone replacement treatment Sixty-three women with a diagnosis of TS (mean age, 31.5 years) participated in a cross-sectional study, using interview data, ratings on the Psychological General Well-being (PGWB) Index, and data from medical examinations and medical records. Statistical analysis was performed by bivariate and multivariate analyses. Lack of sex hormones during adult life and the presence of hearing impairment were related to lower psychological well-being, as were higher age at diagnosis, higher age at menarche or induced bleeding, higher chronological age and retrospectively reported difficulties with school subjects. Age at diagnosis and difficulties with school subjects explained 25% of the variation in psychological well-being. This study has identified some correlates to psychological well-being in women with TS, which are important when considering the clinical management of adult women with TS.

Genetic analysis of mosaicism in 53 women with Turner syndrome.

Mosaicism involving the sex chromosomes is a common finding in women with Turner syndrome (TS). It is especially important to detect Y-chromosomal material, since this is a risk factor for the development of gonadoblastoma. Recent studies have also indicated that the frequency of 45,X cells may be used to predict prognosis. As part of an ongoing multi-disciplinary study, we have examined the extent of Y-chromosomal material and sex chromosomal mosaicism and its tissue specificity in 53 women with TS. The results of lymphocyte karyotyping were compared with the use of interphase X/Y fluorescence in situ hybridisation (FISH) analysis of lymphocytes and buccal mucosal cells. As could be expected, an extended FISH analysis detected more Y-chromosomal material than karyotyping (in 15% vs. 11% of the women, respectively) and also detected more X-chromosomal mosaicism among the TS women (in 70% vs. 45 % of the women, respectively). In half of the women, tissue-specific differences between lymphocytes and buccal mucosal cells were found. Based on these results, we suggest the use of X/Y interphase FISH as a complement to karyotyping in order to obtain a more complete knowledge of the chromosome constitution of each individual with TS.

Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome.

Turner syndrome (TS) is caused by an X chromosome aberration and is characterized by endogenous estrogen deficiency secondary to ovarian dysgenesis and short stature. Our aim was to study the prevalence of cardiovascular malformations and cardiovascular risk factors (blood pressure, blood lipids and glucose, coagulation factors, social factors, smoking habits) in adults with Turner syndrome in comparison with a female random population sample. One hundred women with Turner syndrome (aged 16-71 yr) underwent physical examination, echocardiography, electrocardiography, and blood sampling. Seventy-one of them were matched for age [mean age, 33.7 +/- 11 yr (range, 25-64)] with a random population sample (n = 213) of women [mean age, 34.8 +/- 9 yr (range, 25-64)] from the World Health Organization's Monitoring of Trends and Determinants in Cardiovascular Diseases Project, Göteborg. Six percent of Turner syndrome women were smokers compared with 25% in the population (P < 0.001). Turner syndrome women were relatively heavier and had a lower degree of leisure time physical activity than controls (P < 0.001). Diabetes and treatment for hypertension were present in 3 and 22% among Turner syndrome women vs. 2% (not significant) and 3% (P < 0.001) in controls, respectively. Cardiovascular malformations were found among 17% in Turner syndrome women (45,X dominated) vs. 0.5% in controls (P < 0.001). Systolic but not diastolic blood pressure was higher in Turner syndrome women. No differences were seen in serum total cholesterol, high- or low-density lipoprotein cholesterol, triglycerides, lipoprotein (a), or plasma fibrinogen concentrations between patients and controls. Diabetes or hypertension was not related to karyotype. In conclusion, congenital cardiovascular malformations were frequent. Most cardiovascular risk factors (glucose and lipid levels, fibrinogen, smoking habits) were not increased, but hypertension was more common in Turner syndrome women.

Women with Turner syndrome: psychological well-being, self-rated health and social life.

Psychological well-being, self-rated health and social situation were investigated in a cross-sectional multidisciplinary study of 63 women with Turner syndrome (TS; mean age 31.5 years, range 18-59 years). The psychological examination included a semi-structured interview, and use of two standardized self-rating scales, the Psychological General Well-being Index (PGWB) and the Nottingham Health Profile (NHP). Psychological well-being and self-rated health were similar in the women with TS and Swedish female normative data, matched for age. However, the women with TS reported more social isolation than the normative group. Within the TS group, the oldest women reported more psychological distress and poorer health than the youngest. Those with impaired self-rated health reported more emotional distress. The women with TS were studying or in employment to the same degree as the general population, although fewer were cohabiting. In the interview, both negative and positive consequences of TS were reported. This study did not find any evidence for impaired psychological well-being, although it did indicate that women with TS experience more difficulties in the area of social and partner relationships.

Osteoporosis and fractures in Turner syndrome-importance of growth promoting and oestrogen therapy.

OBJECTIVE: Turner syndrome (TS) is a chromosomal aberration (45,X) characterized by endogenous oestrogen deficiency and short stature. The aim was to study body composition, bone mineral density, fracture frequency, social and life style factors and biochemical bone markers, as well as hormones, in adults with TS in comparison with a female random population sample. PATIENTS: Seventy women with TS responded to questionnaires. They underwent physical examination, bone mineral density measurement with Dual Energy X-ray Absorptiometry (DEXA) and blood sampling. Mean age was 31 +/- 12 (range 16-71) years. A random population sample of women from the WHO MONICA Project, Göteborg (25-64 years) served as controls (n = 740). RESULTS: Women with TS were shorter than the controls and had lower body weight and lean body mass (P < 0.0001). Body mass index and waist/hip circumference ratio were higher in TS (P < 0.0001). Osteoporosis was present in seven TS women, six above 45 years of age. None of these had received oestrogen substitution continuously. Fractures (all types) were reported by 11 (16%) TS women (six (50%) above 45 years) compared with 5% in the population sample (P < 0. 001). Four TS women with fractures had osteoporosis, all above 45 years of age. Osteoporosis and fractures did not differ between women with the 45,X karyotype and those with mosaicism. Impaired hearing was reported by 40%, and 73% wore glasses. Six percent among TS were smokers compared with 25% in the population (P < 0.001). TS women reported a lower degree of leisure time physical activity than controls (P < 0.001). Parathyroid hormone and osteocalcin were higher among TS (P < 0.02 and 0.001). Insulin-like growth factor-I was similar. Ninety-one percent of all TS had oestrogen substitution and 96% of TS below 25 years of age had received growth hormone treatment. CONCLUSION: Osteoporosis and fractures were common above, but not below, 45 years of age in Turner syndrome. It is probable that modern therapy, including growth promoting and continuous oestrogen therapy, will prevent osteoporotic fractures in the future.

Results of gonadotrophin stimulation with the option to convert cycles to in vitro fertilization in cases of multifollicular development.

BACKGROUND: To avoid a high cancellation rate and/or a high multiple pregnancy rate due to multifollicular development in gonadotrophin stimulated cycles, such cycles were converted in the same cycle to in vitro fertilization/embryo transfer (IVF/ET). The results from a four year period using this strategy are summarized. PATIENTS AND METHODS: Seventy-three anovulatory women (seven WHO group I, 66 WHO group II) were studied during this period. In a majority of the cycles a GnRH-analogue was used for down-regulation according to a long protocol, followed by stimulation with FSH and/or hMG. RESULTS: Out of 154 WHO group II gonadotrophin stimulation cycles intended for ovulation induction, 25 cycles were converted to IVF. The pregnancy and delivery rates in the IVF-converted cycles were 50% and 41%, respectively, and 31% and 22% when gonadotrophin stimulation was followed by intercourse. The cancellation rate, including both ovulation induction and IVF cycles, was 15% and the multiple pregnancy rate was 30%, mainly twins. Lean women achieved better outcome than obese women. In WHO group I only 12 cycles were performed. One cycle was converted to IVF resulting in delivery and one cycle was cancelled. The pregnancy- and delivery rates were both 50% when gonadotrophin stimulation was followed by intercourse. CONCLUSION: It is concluded that the option to convert a gonadotrophin stimulation cycle to IVF in the same cycle, in cases of multifollicular development, seemed to be a good alternative. The conversion results in a low cancellation rate and a low incidence of high order multiple pregnancies. Patients should be informed of this opportunity before entering ovulation stimulation.

Treatment, failures and complications of ectopic pregnancy: changes over a 20 year period.

Data from all 225 women operated on for ectopic pregnancy in 1992-1994 at Sahlgrenska University Hospital were collected and compared with three previous cross-sectional investigations from our hospital (1975-1979, 1981-1982 and 1986-1987) in order to evaluate the extent to which surgical treatment and post-operative complications have changed over a 20 year period. Laparoscopic surgery, which was not possible in the 1970s, was used in almost 85% of the ectopic pregnancies in 1992-1994. Conservative treatment was still the most frequently used technique. The complication rate was 1.2% in 1975-1979 when only laparotomies were carried out. After the introduction of laparoscopic surgery (1986-1987), the complication rate rose significantly (7.3%) and continued to increase even when this procedure was established as routine (14.2% in 1992-1994). Post-operative complications were most frequent after conservative laparoscopic surgery (24.4%) while there were no complications after laparotomies. In spite of increasing complication rates the frequency of patients in pre-shock, as well as the proportion of patients with heavy intra-abdominal bleeding and tubal rupture, decreased over time.

The expectant management of early pregnancies of uncertain site.

The role of expectant management was evaluated in 80 women in whom clinical examination, including vaginal ultrasound, had failed to identify the location of an early pregnancy. In 45 cases, spontaneous resolution of the pregnancy products occurred. A normal intra-uterine pregnancy was diagnosed in 12 patients. A total of 23 patients underwent active therapeutic measures due to an ectopic pregnancy (n = 16) or a spontaneous abortion (n = 7). The effectiveness of different diagnostic measures to identify patients suitable for expectant management was analysed. In 33/34 patients (97%) with a relative daily human chorionic gonadotrophin (HCG) change of < -5%, and a serum progesterone concentration of < 20 nmol/l, spontaneous resolution of the pregnancy products occurred. Among 46 cases, with a relative daily HCG change of > -5% and/or serum progesterone > 20 nmol/l, active therapeutic measures were carried out in 22 cases (48%), a normal intra-uterine pregnancy was diagnosed in 12 cases (26%) and spontaneous resolution of the pregnancy products occurred in 12 cases (26%). In conclusion, the combination of a single progesterone assay and serial HCG determinations retrospectively identified early pregnancies of uncertain location in whom expectant management was a safe management option.

Background factors and scoring systems in relation to pregnancy outcome after fertility surgery.

BACKGROUND: A study was initiated to identify background factors, clinical features and pre-operative scoring systems of importance for future selection of patients suitable for fertility surgery. METHODS: Surgical procedures, background factors and scoring systems for tubal lesions and adnexal adhesions and risk factors for ectopic pregnancy were analyzed with respect to possible correlation to subsequent fertility in a retrospective study of 246 patients undergoing fertility surgery (adhesiolysis, salpingostomy, tubal anastomoses, implantation and myomectomy) between 1986 and 1990. Follow-up periods varied between one to six years. RESULTS: In 94% of cases a second look laparoscopy was performed. Adhesiolysis was done in 62%. The conception rate was 41.1%, the ectopic pregnancy rate was 14.6% and the delivery rate was 22.0%. Myomectomy procedures were most successful, with a delivery rate of 44.0% and no ectopic pregnancy. Previous ectopic pregnancy indicated a higher risk for recurrence, as did a high risk score for ectopic pregnancy. The extent of tubal damage was most relevant to subsequent fertility. Salpingostomies in women with mild or moderate tubal damage resulted in a delivery rate of 25.4% compared with those with severe damage (5.6%). No deliveries were seen after lysis of extensive adnexal adhesions. CONCLUSION: Adhesion formation is not negligible and a second look laparoscopy is recommended. Women with fibroids should always be considered for fertility surgery, not only because of high success rates, but also as an adjuvant to subsequent in vitro fertilization. Patients with previous ectopic pregnancy, extensive adhesions and unfavorable tubal scores should not be considered for surgery but referred for in vitro fertilization.

Dilapan tent-gemeprost regimen vs. combinations of extra-amniotic Rivanol-Laminaria/Lamicel and oxytocin for second trimester abortion.

OBJECTIVE: To compare a new regimen for second trimester abortion using Dilapan and vaginal gemeprost suppositories with extra-amniotic Rivanol instillation and oxytocin i.v. immediately or 16 h after instillation. METHODS: A prospective study was performed in 153 women to analyze the induction-abortion interval, the use of analgesics and the complication rate. Wilcoxon's rank sum test was used for statistical evaluation. RESULTS: The mean induction-abortion interval was significantly shorter in the Dilapan-gemeprost-treated women than in the immediate or 16-h Rivanol-oxytocin-treated women, 12.5 vs. 23.3 and 26.8 h, respectively. The 24-h cumulative abortion rate was 91% in the former group vs. 49% and 61%, respectively. The use of analgesics was less frequent among the Dilapan-gemeprost-treated women, whereas the complication rate did not differ. CONCLUSIONS: The Dilapan-gemeprost treatment was advantageous with respect to a shorter induction-abortion interval and ease of handling. However a minority of women do not respond to this treatment and it is therefore necessary to employ alternative methods to complete the abortion in these cases.

Low-dose oral methotrexate as second-line therapy for persistent trophoblast after conservative treatment of ectopic pregnancy.

The aim of this study was to evaluate the efficacy of methotrexate as second-line treatment for ectopic pregnancy. Oral methotrexate was used in 15 patients with evidence of persistent trophoblast after conservative laparoscopic surgery for tubal pregnancy. The treatment was successful in 14 of 15 cases, and the mean time for decline of serum hCG to nonpregnant levels was 24 days. In the remaining case, hCG continued to rise. Side effects were noticed, even at a low dosage, but only in those subjects not receiving citrovorum rescue. As an alternative to a second operation, oral methotrexate appears to be an effective and well-tolerated therapy for persistent trophoblast.

Differential diagnosis of early human pregnancies: impact of different diagnostic measures.

A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies.

Distinction between early normal intrauterine pregnancies and pathological pregnancies by means of a logistic model.

The probability of an unclear very early pregnancy being a normal intrauterine pregnancy was estimated using a logistic model. Five diagnostic measures of prognostic value were identified in the model: (i) daily change in human chorionic gonadotrophin (HCG), (ii) results of transvaginal ultrasound, (iii) vaginal bleeding, (iv) serum progesterone level and (v) risk score for ectopic pregnancy. With the use of this model, the probability of a normal intrauterine pregnancy has been estimated as 96.7%.

Neuropeptide Y, its localization in the human cervix and possible effect on the contractile activity of cervix smooth muscle.

Immunochemical methods were used to identify neuropeptide Y (NPY) in the cervical tissue of women at early and term pregnancy. NPY-containing fibers could not be demonstrated in the upper and lower uterine segments at term, but the cervical innervation persisted during labor. Moreover, NPY alone did not affect cervical contractile activity, although the stimulatory effect of noradrenaline was enhanced.

Adenosine 3',5'-monophosphate in relation to inhibition of cervical smooth muscle activity in early pregnant women.

Contractile activity was registered in strips of cervical tissue obtained by needle biopsy from women in the first trimester of pregnancy. Dibutyryl cyclic adenosine-3',5'-monophosphate (5 x 10(-6) mol/l), isobutyryl methylxanthine (10(-4) mol/l), and forskolin (10(-5)-10(-4) mol/l), the latter two drugs known to increase the levels of endogenous cAMP, inhibited spontaneous muscle activity. The levels of tissue cAMP were determined in strips during relaxation induced by prostaglandin E2 or purified porcine relaxin and compared with cAMP levels in strips from the same women during contractile activity. Exposure to prostaglandin E2 but not to relaxin was followed by increased levels of cAMP. It is suggested that cAMP has a role as a second messenger in the prostaglandin E2-mediated relaxation of cervical smooth muscle.