[Show abstract][Hide abstract] ABSTRACT: Context: In adult women, Anti-Müllerian hormone (AMH) is produced by small growing follicles, and circulating levels of AMH reflect the number of antral follicles as well as primordial follicles. Whether AMH reflects follicle numbers in healthy girls remains to be elucidated. Objective: To evaluate if serum levels of AMH reflects ovarian morphology in healthy girls. Design: Population-based cohort study. Setting: General community. Participants: 121 healthy girls aged 9.8 - 14.7 years. Main outcome measures: Clinical examination, including pubertal breast stage (Tanner´s classification B1 - 5). Ovarian volume as well as the number and size of antral follicles were assessed by two independent modalities: A) Magnetic resonance imaging (MRI): Ellipsoid volume, follicles ≥ 2mm, and B) Transabdominal ultrasound (TAUS): Ellipsoid- and 3D volume, follicles ≥ 1mm. Circulating levels of AMH, inhibin B, estradiol, FSH and LH were assessed by immunoassays; testosterone and androstenedione by LC-MS/MS. Results: AMH reflected the number of small (MRI 2 - 3mm) and medium (4 - 6mm) follicles (Pearson´s Rho (r) = 0.531 and r = 0.512, p<0.001) but not large follicles (≥ 7mm) (r = 0.109, p=0.323). In multiple regression analysis, small and medium follicles (MRI ≤ 6mm) remained the main contributors to circulating AMH (Beta 0.501, p<0.001) whereas the correlation between AMH and estradiol was negative (Beta -0.318, p=0.005). In early puberty (B1 - B3), the number of AMH-producing follicles (2 - 6mm) correlated positively with pubertal stages (r=0.453, p=0.001), whereas AMH levels were unaffected (-0.183, p=0.118). Conclusions: Similarly to adult women, small and medium antral follicles (≤ 6mm) were the main contributors to circulating levels of AMH in girls.
[Show abstract][Hide abstract] ABSTRACT: Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T(4) are the most consistent indication of maternal and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T(4) levels.
[Show abstract][Hide abstract] ABSTRACT: Treatment of Graves' disease during pregnancy with antithyroid drugs (ATDs) poses a risk of inducing hypothyroidism and, thus, development of a goiter to the fetus.
We report two patients referred to our department after discovery of a fetal goiter by ultrasound examination in the second trimester of pregnancy. The women receiving 400 mg/day propylthiouracil and 10 mg/day thiamizole, respectively, had thyrotropin and total thyroxine values within the normal reference range but a lowered free thyroxine level. Fetal blood sampling by cordocentesis revealed severe fetal hypothyroidism as the cause of goiter development. Reduction of maternal ATD dose and injection of levothyroxine intra-amniotically quickly reduced the goiter size, and both babies were born euthyroid and without goiters.
Two pregnant women with Graves' disease were overtreated with ATDs inducing iatrogenic goiter in the fetuses. Successful treatment with intra-amniotic levothyroxine injections rendered the babies euthyroid and nongoitrous at birth.
Correct interpretation of thyroid function tests during pregnancy in general--and during ATD therapy of Graves' disease in particular--is difficult. Awareness of pregnancy-related changes in maternal thyroid status, and a close teamwork among endocrinologists, obstetricians, and experts in fetal medicine, is pivotal in ensuring normal growth and development of the unborn child of these patients.
Thyroid: official journal of the American Thyroid Association 01/2011; 21(1):75-81. DOI:10.1089/thy.2010.0286 · 4.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking.
The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories.
The study took place at University Hospital, Copenhagen, Denmark.
The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1-8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2-8.5) yr] who were studied cross-sectionally.
Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand.
Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4-3.6) vs. 1.0 (0.4-2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3-5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6-1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4-153.0) vs. 115.0 (53.1-202.1); P < 0.001].
Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation.
Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex.
Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS.
Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies.
Ultrasound in Obstetrics and Gynecology 05/2007; 29(5):517-26. DOI:10.1002/uog.3918 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the performance of screening for Down syndrome (DS) and other major chromosomal abnormalities using nuchal translucency (NT), free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a prospective study of a non-selected population.
Of 9941 women with an early ultrasound examination, NT was measured in 8622 singleton pregnancies with a gestational age between 10 + 3 and 13 + 6 weeks. beta-hCG and PAPP-A were analyzed in 6441 cases. Detection rates (DR) and false-positive rates (FPR) for the NT screening, the double test (beta-hCG and PAPP-A) and the combined test (NT and the double test) were calculated using a 1 : 250 cut-off.
NT could be measured in 97.5% of cases. The DR for DS with NT screening alone was 75% with a FPR of only 1.8%. The double test detected 73% and the combined test 91%, for FPRs of 8.8% and 2.1%, respectively. We detected 80% of fetuses with other major chromosomal abnormalities with a combination of NT screening and other ultrasound findings. Low beta-hCG and PAPP-A values (below 0.4 MoM) were observed in 0.5% of the women including all cases of triploidy and trisomy 18 and 13.
The performance of a screening strategy for DS using a combination of NT and the double test was superior to that using either NT or the double test alone due to a very low FPR and a higher DR.
Ultrasound in Obstetrics and Gynecology 04/2005; 25(3):227-33. DOI:10.1002/uog.1834 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a case of a 25-week fetus with severe bilateral pleural effusion, marked ascites, skin edema, an anterior thick (hydropic) placenta and polyhydramnios in which the most probable diagnosis was congenital chylothorax. Treatment with a pleuroamniotic shunt was planned, however the location of the fetus just below the anterior placenta made the placement of the shunt too dangerous. We therefore decided to use intrapleural injection of OK-432. From week 29, the lungs looked normal, the pleural effusion had resolved and the thoracic circumference was within normal limits. The severe ascites persisted throughout the pregnancy and a total volume of 3680 mL was removed on several occasions. A Cesarean section was performed at 38 weeks and a normal male was delivered. Continuous positive airway pressure was needed on the first 4 days but after a week the situation was stable. On day 8, an X-ray showed normally developed lungs. OK-432 appears to have prevented pulmonary hypoplasia in our patient.
Ultrasound in Obstetrics and Gynecology 02/2003; 21(1):66-9. DOI:10.1002/uog.23 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Female survivors of cancer in childhood and adolescence who have been treated with bone marrow transplantation including total body irradiation (TBI) are at high risk of developing ovarian follicular depletion and infertility. The lack of oocytes may be compensated for by oocyte donation but these patients also seem to have a uterine factor. Even though oestrogen replacement therapy is given, the growth of the uterus during adolescence is impaired. To our knowledge there have been no earlier reports of live births after oocyte donation in such patients. We report three cases of oocyte donation in women who, at a young age, were cured of haematological malignancies with bone marrow transplantation including TBI. In adolescence they developed ovarian failure and uterine volumes were assessed by ultrasonography. One woman with a uterus of almost normal size delivered a healthy child in the 37th week of gestation. Another woman with severely diminished uterine volume miscarried in the 17th week of gestation. The third woman has not yet conceived. Pregnancy achieved by oocyte donation is possible despite TBI in adolescence. However, the uterine factor is a concern and complications during pregnancy and preterm birth may be expected in these patients.
Human Reproduction 08/2000; 15(7):1505-8. DOI:10.1093/humrep/15.7.1505 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of multiple pregnancy has increased by 1.7 times from 1980-1994. Twenty-five percent of all twins are monochorionic diamnionic. The perinatal mortality of monochorionic twins is five times greater than that found in dichorionic twins and the morbidity is eight times greater. The increase in morbidity is due to prematurity, cerebral lesions and congenital malformations. One of the reasons for the increased morbidity is twin-twin transfusion syndrome (TTTS). TTTS occurs in 10-30% of monochorionic twins. TTTS can be treated by either amniocenteses or by lasercoagulation of anastomoses in the placenta. This paper describes the syndrome and reviews the literature. A multination randomized study is necessary to decide which treatment should be preferred.
[Show abstract][Hide abstract] ABSTRACT: Twin-to-twin transfusion syndrome was found by ultrasound in monochorionic diamniotic twins in week 20. The donor had hydrocephalus and the recipient was normal. Selective foeticide was performed by coagulating the vessels of the umbilical cord of the donor with a YAG-laser. The pregnancy continued without complications and a healthy girl was born in week 34. The birth weight was 2935 g. Psychomotor development was normal at the age of six months.
[Show abstract][Hide abstract] ABSTRACT: Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0-10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and 21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to -2.6 standard deviation scores (SDS) (-6.3 to -0.6), P = 0.002, and -2.6 SDS (-4.8 to -0.5), P = 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated.
Bone Marrow Transplantation 03/1999; 23(3):259-63. DOI:10.1038/sj.bmt.1701569 · 3.57 Impact Factor