research interest

Gynaecological Oncology

Perinatology

Prenatal Diagnosis & Conselling

Reproductive Medicine

Staff
Dr. M. Tang
Dr. E.T. Lau
Dr. C.P. Lee
Dr. K.Y. Leung
Dr. C. Ong
Dr. P.W. Hui
Dr. M. Chen
Dr. B Chan
Ms. V Chan
Ms. YP Lee  

Ultrasonographic assessment of pregnancies at risk of homozygous a0 -thalassaemia
Our centre has demonstrated fetal cardiac and placental enlargement as early as 12 weeks in fetuses affected by homozygous α 0 -thalassaemia with ultrasonography. We have collaborated with a centre in Mainland China to study the usefulness of serial ultrasound examination (non-invasive approach) to predict the disease from 12 weeks of gestation, and found that the non-invasive approach can be applicable in another centre.

Enlarged placenta in a pregnancy complicated by fetal homozygous α 0 -thalassaemia at 12 weeks.	Cardiac enlargement of a foetus with homozygous α 0 -thalassaemia at 12 weeks.

With the introduction of three-dimensional sonography, we have conducted a pilot study on the measurement of the placental volume before 12 weeks of gestation to predict pregnancies affected by homozygous α0 -thalassaemia. Although the placental volume in affected pregnancies was greater than that in unaffected pregnancies, there was no good cut-off point to differentiate between them.

Three-dimensional ultrasonography of an unaffected pregnancy (left side) and an affected pregnancy (right side) at 10 weeks' gestation.

Ultrasound and biochemical screening for fetal Down's syndrome
Down' syndrome is the commonest inborn cause of mental retardation. The disease is not amenable to treatment. Integrated screening combining the first trimester nuchal translucency measurements, second trimester biochemical markers (MSAFP and hCG) and maternal age achieved a detection rate of 85% at a false positive rate of 5%. Using maternal age with nuchal translucency or with second trimester biochemical markers achieved only a 65% detection rate at the same false positive rate. We have conducted a multicentre demonstration trial on integrated screening for fetal Down's syndrome to see whether integrated screening is acceptable to local women and to study the performance of this screening in actual practical settings. We also plan to incorporate first trimester serum markers to the integrated screening to improve the detection rate.

Increased nuchal translucency at 12 weeks of a foetus with Down's syndrome

There have been reports on the usefulness of using the detection or measuring the length of the fetal nasal bone in screening for Down's syndrome. We have conducted a pilot study to examine the inter-observer and intra-observer variabilities in the detection and measurement of fetal nasal bone. It seems that the examinations and measurements are repeatable, and the fetal nasal bone is shorter in Chinese than in Caucasian. We are conducting studies on the normal range of the fetal nasal bone length in Chinese, and the effectiveness of using the fetal nasal bone test, either alone or in combination with other tests in the prenatal screening for Down's syndrome.

Presence of nasal bone	Absence of nasal bone

An increase in the second trimester level of maternal serum hCG and a reduction in the level of AFP was observed in pregnancies after in-vitro fertilization. This resulted in a higher false positive rate in screening for Down's syndrome and posed the women to the risk of invasive diagnostic tests. The exact mechanism for these differences is unclear. We are studying the levels of first trimester (PAPP-A and free b -HCG) and second trimester (MSAFP and hCG) biochemical markers in pregnancies conceived after various modalities of subfertility treatment to see if appropriate adjustment in the current screening program would be necessary for these pregnancies.

Early ultrasound detection of fetal structural abnormalities
We have completed a multicentre, randomized control trial to compare the effectiveness of 13-14 week ultrasound examination to the conventional 18-20 week examination to further assess the potential of first-trimester ultrasound screening for fetal abnormalities in local population. 8926 cases had been recruited. In the study group 30 structural abnormalities were detected at 12-14 weeks ultrasound examination (detection rate 47.6%) and 12 additional ones (detection rate 19%) were detected at 18-23 weeks ultrasound examination. The overall detection rate at the first and second trimester scan was 66.7%. Meanwhile, in the control group, detection rate in the first trimester dating scan was 32.8%. The overall detection rate of structural abnormalities at the first and second trimester was 64.1%. We are exploring collaboration with centres in mainland China for studies in detection of fetal abnormalities in first trimester.

Are herbal medicinal products more teratogenic than Western pharmaceutical products?
More than 10% of pregnant women in various countries reported the use of herbal medicinal products for various reasons. Although consumers often think that herbal medicinal products are risk free, the evidence available to date suggests that some herbal medicinal products are associated with risks. Our centre has performed a retrospective small study to compare the differences in fetal outcomes between women who took herbal medicinal products and women who took Western pharmaceutical products in pregnancy. There was no significant difference in the prevalence of fetal abnormalities between them. We are conducting a prospective study on the effect of herbal medicinal products in pregnancy.

Prenatal counselling on Down syndrome screening
We have developed an interactive multimedia decision aid (IMDA) for the prenatal counselling on Down syndrome screening. We found that the use of IMDA did not affect women's uptake rate of the prenatal screening test for Down syndrome. More women less than 35 accepted IMDA probably because they used computer more frequently and had more computer knowledge.

In collaboration with the Department of Linguistics of the University of Hong Kong , we are conducting a study on communication between doctors/nurses and pregnant women in counselling on Down syndrome screening. We hope to better understand the communication patterns between doctors/nurses and patients through this project and identify aspects of communication that need improvement.

Clinical application of Rapid Aneuploidy Screening (RAS) for chromosomes 21, 18, 13, X & Y
The accuracy of new molecular diagnostics, FISH or QF-PCR (collectively known as rapid aneuploidy screening, RAS), in prenatal diagnosis has already been demonstrated in a number of large studies. We have also confirmed their accuracy in our laboratory. The result can be available within 24 to 48 hours compared to that of 2 to 3 weeks with traditional karyotyping.

Rapid aneuploidy screening using quantitative fluorescence PCR with small tandem repeating markers showing trisomy 21 from amniotic fluid. Red arrows showed diallelic pattern with ratio 2:1 or triallelic patterns with ratio 1:1:1

Hematopoietic stem cell culture from umbilical cord blood and DNA repair for point mutation
Hematopoietic stem cells (HSC) are capable of self-renewal and differentiating into cells of all blood lineages. The ability to culture and cryopreserve HSC from cord blood may have potential use in (multiple) in utero transplantation for blood disease. Combined with mutation repair, therapy for selected blood disorder with expanded stem cells may become a reachable goal.

We have optimised the expansion of HSC from cord blood and aim to investigate target repair of point mutation using expanded cells from individuals with beta thalassemia.

Marker Study
A combination of biochemical and sonographic markers from the first to the third trimesters is a novel approach that could address the pathophysiological aspects of complicated pregnancies. Expressions of IGFs and IGFBPs would be examined in the placentae of all cases and controls to correlate with evidence of clinical placental hypertrophy. Analysis will be performed in relation to the actual infant outcome in terms of birthweight percentile ranking and perinatal complications. The results could provide the basis for the construction of a clinical scoring system utilizing biochemical and sonographic markers to identify pregnancies at risk of different complications in a manner similar to the use of biochemical and sonographic markers in the screening for chromosomal defects.

Use of three-dimensional ultrasound in prenatal diagnosis
We have performed a study on the use of Three-dimensional Extended Imaging TM (3DXI), a new post processing program, in examination of normal and abnormal structures, and found that 3DXI can provide additional information from 2D ultrasound examination.