Ann Thuring

Autotransplantation of cryopreserved ovarian tissue to the right forearm 4(1/2) years after autologous stem cell transplantation.

Premature ovarian failure (POF) may occur as a consequence of chemotherapy and of irradiation to the ovaries (1). Alkylating agents such as cyclophosphamide and chlorambucil are particularly prone to cause ovarian damage (2). The human oocytes are extremely sensitive to radiation. Recently, it was estimated that the radiation required to destroy 50% of the oocytes in human ovaries is less than 2 Grey (3). Besides cryopreservation of embryos and of unfertilized oocytes, cryopreservation of ovarian tissue harvested prior to gonadotoxic treatment is one approach to try to preserve a patient’s fertility. Thus, investigators have reported autotransplantation of fresh ovarian tissue to the forearm (4) and of cryopreserved ovarian tissue heterotopically to the retroperitoneum (5), the rectus abdominis muscle (6) or orthotopically to the remaining ovary (7,8). Recently, Byskov et al. transplanted cryopreserved ovarian tissue to the remaining ovary and could later obtain mature oocytes from the transplant (8). Oktay et al. transplanted cryopreserved ovarian tissue beneath the skin of a woman’s abdomen and succeeded in fertilizing a mature oocyte obtained from the transplant (9). Similarly, Lee et al. obtained mature oocytes from cryopreserved ovarian tissue transplanted to subcutaneous pockets of macaque monkeys. One monkey delivered a healthy female infant at the end of 2003 following in vitro fertilization (IVF) of an oocyte obtained from an abdominal pocket (10). The present report describes the first autotransplantation of cryopreserved ovarian tissue to the forearm of a woman.

Early intervention in management of very preterm growth-restricted fetuses: 2-year outcome of infants delivered on fetal indication before 30 gestational weeks

To describe the outcome of growth‐restricted fetuses with absent or reversed end‐diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks.

Effect of maternal betamethasone on fetal and uteroplacental blood flow velocity waveforms

To investigate the effects of antenatal betamethasone on fetal and uteroplacental hemodynamics.

Ductus venosus blood flow velocity waveform in diabetic pregnancies

Maternal diabetes during pregnancy is associated with congenital cardiac malformations and hypertrophic cardiomyopathy. Blood flow in the ductus venosus (DV) has been postulated to reflect cardiac function. The aim of our study was to investigate if diabetic pregnancies exhibit abnormal DV hemodynamics, hence indicating changes in fetal cardiac function.

Uterine venous blood flow in normal and complicated pregnancies: a methodological study.

To investigate the possibility of recording Doppler flow signals from the maternal uterine veins (UtVs) during pregnancy and to assess the relationship between UtV signals and other Doppler parameters as well as pregnancy outcomes.

Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics.

Objective: To relate Doppler velocimetry findings in fetoplacental and uteroplacental circulation to placental histomorphology. Material and methods: In 14 uncomplicated and 31 high-risk pregnancies Doppler velocimetry was performed in umbilical artery and vein, and in maternal uterine veins and arteries during the second half of gestation. Histopathology of the placentas was examined, especially for signs of ischemia and inflammation. Results: All fetuses in uncomplicated pregnancies had normal flow velocity waveforms in umbilical artery; in the high-risk group, 18 fetuses had abnormal flow (increased PI or absent/reverse end-diastolic flow). The latter group had more often high ischemic score and infarctions in the placenta than found in pregnancies with normal umbilical artery flow (p < 0.001 and p = 0.02, respectively). Similarly, the abnormal uterine artery flow pattern (uterine artery score 3–4) occurred more often with high ischemic score and placenta infarctions (p < 0.001 and p < 0.001, respectively). No significant associations were found between the uterine venous flow type and placental ischemia. Conclusion: Placental ischemic morphological changes were associated with Doppler ultrasound signs of increased resistance to arterial blood flow, both on the fetal and maternal sides of the placenta. No significant relation to the uterine venous flow velocities was found.

Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material.

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high‐risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in an animal model. In the present pilot study, the method was for the first time applied to human pregnancies. Doppler umbilical artery velocimetry was performed in 13 preterm fetuses before and after two doses of 12 mg betamethasone. The auditory measure defined by the frequency band where the spectral energy had dropped 15 dB from its maximum level (MAXpeak‐15 dB), increased two days after betamethasone administration (p = 0.001) parallel with a less pronounced decrease in PI (p = 0.04). The new auditory parameter MAXpeak‐15 dB reflected the changes more sensitively than the PI did.

Operator auditory perception and spectral quantification of umbilical artery Doppler ultrasound signals.

Objective An experienced sonographer can by listening to the Doppler audio signals perceive various timbres that distinguish different types of umbilical artery flow despite an unchanged pulsatility index (PI). Our aim was to develop an objective measure of the Doppler audio signals recorded from fetoplacental circulation in a sheep model. Methods Various degrees of pathological flow velocity waveforms in the umbilical artery, similar to those in human complicated pregnancies, were induced by microsphere embolization of the placental bed (embolization model, 7 lamb fetuses, 370 Doppler recordings) or by fetal hemodilution (anemia model, 4 lamb fetuses, 184 recordings). A subjective 11-step operator auditory scale (OAS) was related to conventional Doppler parameters, PI and time average mean velocity (TAM), and to sound frequency analysis of Doppler signals (sound frequency with the maximum energy content [MAXpeak] and frequency band at maximum level minus 15 dB [MAXpeak-15 dB] over several heart cycles). Results We found a negative correlation between the OAS and PI: median Rho −0.73 (range −0.35– −0.94) and −0.68 (range −0.57– −0.78) in the two lamb models, respectively. There was a positive correlation between OAS and TAM in both models: median Rho 0.80 (range 0.58–0.95) and 0.90 (range 0.78–0.95), respectively. A strong correlation was found between TAM and the results of sound spectrum analysis; in the embolization model the median r was 0.91 (range 0.88–0.97) for MAXpeak and 0.91 (range 0.82–0.98) for MAXpeak-15 dB. In the anemia model, the corresponding values were 0.92 (range 0.78–0.96) and 0.96 (range 0.89–0.98), respectively. Conclusion Audio-spectrum analysis reflects the subjective perception of Doppler sound signals in the umbilical artery and has a strong correlation to TAM-velocity. This information might be of importance for clinical management of complicated pregnancies as an addition to conventional Doppler parameters.

OC114: Ductus venosus systolic and early diastolic wave indices: new markers of pre‐terminal changes in cardiac function

Objective: The atrial contraction wave is the single most important component of the ductus venosus (DV) indices used in predicting acidosis and adverse outcome. Based on the assumption that some pre-terminal changes in cardiac compliance and performance are rather reflected in the systolic and early diastolic components of the DV waveform, we aimed to establish and test new indices suitable for clinical use. Methods: DV velocities of 381 low-risk pregnancies were used to establish reference ranges for systolic pulsatility [DV-SPuls = (systolic peak − systolic nadir)/systolic peak] and early diastolic pulsatility [DV-DPuls = (diastolic peak − systolic nadir)/diastolic peak]. The DV-SPuls and DV-DPuls were determined in 123 cases where the DV Doppler recording was done ≤2 days before Cesarean section and where arterial cord pH and base excess (BE) were available at delivery, and in 15 cases of intrauterine fetal death (IUD). Power-transformation was used to achieve normality and fractional polynomial regression to calculate reference ranges, and SD-score statistics to assess deviation from the reference means. P < 0.05 was considered significant. Results: Arterial cord pH < 7.15 (n = 12), BE <−8.7 (n = 10), and particularly IUD (n = 15) were associated with increased DV-SPuls and DV-DPuls (overall p < 0.0001, and no overlap of 95%CI) when compared with the reference population. The DV-SPuls and DVDPuls were particularly high in cases with IUD (means were 2.4 and 3.1 SDs above means for the reference population) and also significantly higher than in fetuses that had arterial cord pH < 7.15 and BE <−8.7 (no overlap of 95%CI). Conclusions: Changes in the ductus venosus waveform during systole and early diastole are linked to alterations in acid base status at birth and intrauterine death. Augmented pulsations in this part of the DV wave may give valuable additional information on pre-terminal deterioration of the fetal circulation.

632 Cardiac Evaluation of Neonates with Impaired Intrauterine Growth

Background and aims. We investigated the relationship between the cardiac function and coronary flow in neonates with impaired intrauterine growth. Methods. Fetal growth was assessed by fetometry and Doppler velocimetry of the umbilical artery blood flow. Impaired fetal growth was defined as an estimated fetal weight less than mean -2SD from the normal gestational age related fetal weight. Cardiac function and left anterior descending artery (LAD) flow parameters were measured by transthoracic Doppler echocardiography in 14 newborns at one week of age when the ductus arteriosus was closed. Gestational age- and age-matched healthy newborns, appropriate for gestational age (N=15) served as controls. Results. The mean pulsatility index was 0.97 and the mean birth weight 2.2 (range 2.1 to 2.4) kg. The left ventricular shortening fraction was normal 39±4.3%. Aortic velocity time integral/minute as a measure of systolic LV function correlated to LAD PFVd, r=0.54, p< 0.0001. LAD peak flow velocity in diastole (PFVd) correlated to left ventricular mass (r=0.46, p=0.0001). The mean LAD diameter was 0.99±0.09 mm. Impaired intrauterine growth was associated with an increase of PFVd (mean 34.5±4, controls 19±6 mm/s, p=0.0001) and coronary flow (7.3±2, and 4.8±2 ml/min respectively, p=0.04). LAD velocity time integral per minute correlated to mitral peak E-wave (r=0.74, p< 0.01). Conclusions. Basal coronary flow and peak flow velocity appear to be significantly increased in these neonates with intrauterine growth impairment, which leads to decreased coronary flow reserve. LAD flow parameters were linearly related to LV systolic and diastolic functions and to LV mass.