A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts.

BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1 deletions that did not arise via homologous recombination but most probably via non-homologous recombination (NHR) between palindromes. In the current study, we set out to identify deletions in the azoospermia factor c (AZFc) region caused by NHR between palindromes. METHODS: We screened 1237 men using plus/minus and quantitative real-time polymerase chain reaction, fluorescence in situ hybridization and Southern blot analyses for deletions caused by NHR. These 1237 men originated from two series: one series of 237 men with azoospermia or severe oligozoospermia and 148 with normozoospermia and one series of 852 consecutively included men of subfertile couples unselected for sperm count. RESULTS: We identified eight unrelated men with deletions caused by NHR. These deletions could be categorized into four classes termed P3a, P3b, P3c and P3d. The P3a and P3b deletions were found in single instances whereas the P3c and P3d deletions were found in three men. Men with a P3c deletion had a higher total sperm count than those without a deletion (median 378.8 × 10(6) versus 153.9 × 10(6), P = 0.040). We did not find an association of the other P3 deletions with altered sperm counts. CONCLUSIONS: We have found a novel subclass of partial AZFc deletions that results from NHR. One deletion, the P3c deletion, might be associated with increased sperm count.

Doppler colour flow imaging of fetal intracerebral arteries relative to fetal behavioural states in normal pregnancy.

In 14 normally developing term fetuses, the relationship between the blood flow velocity waveforms at cerebral arterial level (internal carotid artery, anterior, middle and posterior cerebral artery) and fetal behavioural states was studied using Doppler colour flow imaging. Behavioural state dependent changes in absolute flow velocities occurred in all vessels, except for the middle cerebral artery. These changes suggest preferential blood flow to the left heart resulting in increased flow to the cerebrum during fetal behavioural state 2F (active sleep) when compared with fetal behavioural state 1F (quiet sleep). The middle cerebral artery supplies the neocerebrum. This developing part of the cerebrum does not seem to take part in the regulation of fetal behaviour. In the internal carotid artery, an inverse relationship between peak systolic velocity and fetal heart rate could be established, which can be explained by a shorter rapid filling phase at raised fetal heart rate according to the Frank-Starling Law.

Doppler colour flow imaging of fetal intracerebral arteries and umbilical artery in the small for gestational age fetus.

OBJECTIVE: To assess with Doppler colour flow imaging whether a brain-sparing effect is present in all cerebral arteries of the circle of Willis in the small for gestational age fetus, to determine which cerebral flow velocity parameter is most discriminating in this pathological condition, and to relate this parameter to the umbilical artery pulsatility index. DESIGN: Prospective, cross-sectional, matched case-control study. SETTING: Academic department of obstetrics and gynaecology. SUBJECTS: Twenty-eight small for gestational age fetuses and 28 normal controls at 24 to 38 weeks of gestation. INTERVENTIONS: Blood flow velocity waveforms from the umbilical and fetal intracerebral arteries were studied with Doppler colour flow imaging for measurement of peak systolic, end-diastolic and time averaged velocities, and calculation of the pulsatility index. MAIN OUTCOME MEASURES: Comparison of intracerebral and umbilical artery waveform parameters between small for gestational age fetuses and controls. RESULTS: Acceptable flow velocity waveforms were obtained in the intracerebral circulation in more than 85%. In small for gestational age fetuses, all intracerebral arteries displayed reduced downstream impedance. The end-diastolic velocities of the middle and anterior cerebral artery are the most discriminative factors between small for gestational age fetuses and controls. The highest sensitivity was reached for the umbilical artery pulsatility index. CONCLUSIONS: Doppler colour flow imaging allows easy identification of fetal intracerebral arterial vasculature. Whereas for the intracranial vasculature, the end-diastolic blood flow velocities in the anterior and middle cerebral artery are the most sensitive parameters discriminating between small for gestational age and controls, umbilical artery pulsatility index remains the best indicator for the small for gestational age fetus.

Fetal internal carotid and umbilical artery blood flow velocity waveforms as a measure of fetal well-being in intrauterine growth retardation.

Maximal flow velocity waveforms were recorded on one occasion from the umbilical artery (UA) and fetal internal carotid artery (ICA) in 240 normal pregnancies and 44 cases of intrauterine growth retardation between 26 and 39 wk of gestation. In normal pregnancy the mean UA pulsatility index (PI) decreased from 1.14 (SD: +/- 0.13) at 26-27 wk of gestation to 0.78 (SD: +/- 0.15) at 38-39 wk. The corresponding decrease in ICA PI was from 1.63 (SD: +/- 0.19) to 1.31 (SD: +/- 0.21). Mean values of UA PI for normal pregnancies were linearly related to gestational age; for ICA PI this relation appeared to be quadratic. Normal limits according to age were constructed by estimated means +/- 2 SD. In intrauterine growth retardation, the UA PI was increased (greater than 2 SD) in 80% of cases, ICA PI was reduced (greater than 2 SD) in only 45%. The outcome of fetuses with intrauterine growth retardation, as expressed by fetal heart rate abnormality, Apgar score at 1 min, and umbilical cord pH, was significantly related to the UA PI but not to the ICA PI.

The blood flow velocity waveform in the fetal descending aorta; its relationship to fetal heart rate pattern, eye and body movements in normal pregnancy at 27-28 weeks of gestation.

In 13 normal pregnancies at 27-28 weeks of gestation the blood flow velocity waveform at the lower thoracic level of the fetal descending aorta was studied in relation to fetal heart rate pattern (FHRP), fetal eye movements (FEM) and fetal body movements (FBM). State parameter combinations in which high fetal heart rate (FHR) variability was present, were associated with a significant reduction in pulsatility index (PI) as compared with periods in which low FHR variability was present, irrespective of FEM and FBM, indicating a reduced peripheral vascular resistance. At 27-28 weeks of gestation FHR variability and PI might be linked to baroreceptor sensitivity. PI values derived from combinations FHRP-A, FEM(-), FBM(-) and FHRP-B, FEM(+), FBM(+) showed a significant inverse relationship (P less than 0.05) with FHR. FHR and FHR variability should be taken into account when studying flow velocity waveforms in the fetal descending aorta at 27-28 weeks of gestation.

The blood flow velocity waveform in the fetal internal carotid and umbilical artery; its relation to fetal behavioural states in the growth retarded fetus at 37-38 weeks gestation.

In eight women whose fetuses showed evidence of intrauterine growth retardation (IUGR), the relation was examined between the blood flow velocity waveform in the fetal internal carotid and umbilical artery and fetal behavioural states at 37-38 weeks gestation. In both vessels there was a virtual overlap of pulsatility index values originating from state 1F and 2F, reflecting behavioural state independency. In the internal carotid artery this state independency is associated with moderately reduced pulsatility index values.

The Doppler flow velocity waveform in the fetal internal carotid artery with respect to fetal behavioural states. A longitudinal study.

Doppler flow velocity waveforms in the fetal internal carotid artery were recorded in 21 normal pregnancies during fetal behavioural state IF (quiet sleep) and 2F (active sleep) according to Nijhuis and co-workers, from the 36th week of gestation onwards. The present study confirms the earlier finding of a significant reduction of the pulsatility index (PI) in state 2F as compared to state 1F at 37-38 weeks of gestation and demonstrates that this difference in PI exists throughout the entire period, in which fetal behavioural states have been described. Furthermore, it is demonstrated that there is a significant reduction in PI of this vessel during the last 4 weeks of gestation, suggesting a haemodynamic redistribution, favouring blood supply to the brain during the latter weeks of gestation.

The blood flow velocity waveform in the fetal internal carotid and umbilical artery; its relation to fetal behavioural states in normal pregnancy at 37-38 weeks.

The relation between the blood flow velocity waveform in the fetal internal carotid artery (n = 12) and umbilical artery (n = 15) and fetal behavioural states at 37-38 weeks of gestation was studied. In the fetal internal carotid artery, under standardized fetal heart rate conditions, the pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during behavioural state 2F (active sleep) compared with state 1F (quiet sleep) according to the classification by Nijhuis et al. (1982), suggesting increased fetal cerebral blood flow during state 2F. In the umbilical artery, no significant difference in PI between the two behavioural states could be established. This suggests a fetal origin of the state dependency observed in fetal blood flow velocity waveforms.

Cerebral and umbilical arterial blood flow velocity waveforms in normal and growth-retarded pregnancies.

A combined sector and pulsed Doppler system was used to study the pulsatility index in the fetal internal carotid artery and umbilical artery in 156 normal pregnancies and 42 cases of intrauterine growth retardation (birth weight below the tenth percentile). All pregnancies were in the third trimester. In normal pregnancies, there was a gestational age-related fall in pulsatility index for both the umbilical artery and the umbilical artery/internal carotid artery ratio. No such fall was established for the pulsatility index in the internal carotid artery. In growth-retarded pregnancies, raised pulsatility index values in the umbilical artery were associated with reduced pulsatility index values in the internal carotid artery, suggesting the presence of a "brain-sparing" effect. When fetal causes of growth retardation were excluded, the sensitivities of the pulsatility index in the internal carotid artery, the umbilical artery, and for the umbilical artery/internal carotid artery ratio were 65, 83, and 88% at the 1 standard deviation (SD) cutoff level; and 48, 60, and 70% at the 2 SD cutoff level. Growth-retarded fetuses with structural or chromosomal defects had normal pulsatility index values in the internal carotid artery.

Fetal blood flow velocity waveforms in relation to changing peripheral vascular resistance.

In an acute experiment in Texel ewes, Doppler flow velocity waveforms from the fetal descending aorta were related to peripheral vascular resistance as calculated from perfusion pressure divided by electromagnetically measured volume flow in the descending aorta. Vascular resistance was increased by stepwise embolization of the peripheral circulation via repeated bolus administration of Sephadex G-25 microspheres. A rise in peripheral vascular resistance was associated with a reduction in peak and end-diastolic flow velocity and an increase in Pulsatility Index. Clinically, if similar changes are observed in growth retarded fetuses, the findings are usually interpreted to represent 'uteroplacental insufficiency'. Present data provide direct evidence that raised peripheral vascular resistance does indeed produce such waveform changes.

Fetal cardiac arrhythmias and their effect on volume blood flow in descending aorta of human fetus.

Using a two-dimensional linear array real-time and pulsed Doppler ultrasound system, volume blood flow measurements were made in 86 normal pregnancies, seven cases of fetal bradycardia, and seven cases of fetal tachycardia at the lower thoracic level of the fetal descending aorta. During fetal cardiac arrhythmias, volume blood flow was maintained within the normal range until the heart rates reached around 50 bpm and 230 bpm, after which the volume blood flow diminished. The changes observed suggest that the Frank-Starling mechanism is functional in the fetal myocardium and demonstrate the stability of the fetal circulation.

The blood flow velocity waveform in the fetal descending aorta; its relationship to behavioural states in the growth-retarded fetus at 37-38 weeks of gestation.

In 12 patients with intrauterine growth retardation (IUGR), the relationship between the blood flow velocity waveform at the lower thoracic level of the fetal descending aorta and fetal behavioural states at 37-38 wk of gestation was studied. A significant inverse relationship (P less than 0.001) was established between pulsatility index (PI) and fetal heart rate (FHR) in state 1F and 2F. The PI as a measure of peripheral vascular resistance, demonstrated a marked increase compared to normal pregnancy. There is a virtual overlap of PI values originating from state 1F and 2F according to the classification by Nijhuis et al. (J.G. Nijhuis, H.F.R. Prechtl, C.B. Martin, Jr. and R.S.G.M. Bots (1982) Early Hum. Dev. 6, 177-195). The peripheral vasoconstriction present in IUGR seems to overrule state dependent PI fluctuations. The marked rise in PI, particularly at lower FHR and the constancy of PI in relation to fetal behavioural states can be considered vascular adaptations, which are instrumental in the centralization of the fetal circulation, with the aim of favouring blood supply to the brain, heart and adrenals during IUGR.

Blood flow velocity waveforms in the descending fetal aorta: comparison between normal and growth-retarded pregnancies.

A linear array real-time transducer was combined with a pulsed Doppler transducer to study and compare the mean blood flow velocity waveform in 77 normal pregnancies and 12 cases of intrauterine growth retardation. All pregnancies were in the third trimester. In normal pregnancies the peak velocity, end diastolic velocity, and pulsatile index remained unchanged with increasing gestational age. End diastolic velocity was lowered or at zero level (high pass filter level), and the pulsatile index was elevated in most cases of severe intrauterine growth retardation. Peak velocity related closely with the quality of the heart rate patterns and the condition of the infant at birth.

The blood flow velocity waveform in the fetal descending aorta: its relationship to fetal behavioural states in normal pregnancy at 37-38 weeks.

In 13 normal pregnancies, the relationship between the blood flow velocity waveform at the lower thoracic level of the fetal descending aorta and fetal behavioural states at 37-38 weeks of gestation was studied. The pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during state 2F compared to state 1F according to the classification by Nijhuis et al. (Nijhuis, J.G. et al. (1982) Early Hum. Dev., 6, 177-195), suggesting an increased perfusion of the fetal skeletal musculature to meet the energy demand needed for the raised muscular activity during state 2F; A significant inverse relationship (P less than 0.001) was established between PI and FHR in state 2F; this was mainly determined by a significant rise in end-diastolic flow velocity (P less than 0.02). Both the behavioural state and FHR should be taken into account when evaluating flow velocity waveforms in the fetal descending aorta during the latter weeks of pregnancy.