Isolation of fetal cells from transcervical samples by micromanipulation: Molecular confirmation of their fetal origin and diagnosis of fetal aneuploidy

Transcervical cell (TCC) samples have been shown to contain fetal cells amenable to molecular analysis. However, the presence of ‘contaminating’ maternal cells limits their use for prenatal diagnoses. In this report we show that clumps of fetal cells can be isolated from transcervical samples by micromanipulation and tested by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). Out of 129 clumps, isolated from mucus aspirates and transcervical lavages from 29 patients, 29 clumps from 11 patients were found to be exclusively of fetal origin as judged by the detection of chromosome 21-specific polymorphic DNA markers and Y-derived DNA sequences by PCR and FISH. One case of a male triploid fetus, diagnosed by the analysis of TCC samples obtained by mucus aspiration and lavage, was confirmed by testing clumps of cells isolated by micromanipulation.     

Management of fetofetal transfusion syndrome

Feto-fetal transfusion syndrome contributes heavily to high rates of perinatal mortality and morbidity in monochorionic multiple pregnancies. Its prenatal management has been controversial for at least 25 years. We review the recent literature in order to present the basis for a pragmatic reappraisal of the management of this condition. Laser surgery of the chorionic plate inter-twin anastomoses is the best first-line treatment when the syndrome develops before 26 weeks' gestation. Survival (including quality of survival) and gestational age at delivery are improved when compared to serial amnioreduction. Second-line treatment options include repeat-laser, intra-uterine blood transfusion, serial amnioreduction, selective feticide using bipolar cord coagulation or elective delivery, depending upon gestational age and the severity of the disease and its complications. We have found that fetoscopic placental surgery has proven itself over simplicity of amnioreduction. There is no evidence that treatment should be customized according to the stage of the disease at diagnosis. Early recognition of the syndrome through fortnightly serial ultrasound follow-up of all monochorionic pregnancies should ensure timely referral and make up for geographical constraints. Laser surgery should now be available in fetal medicine units that are managing at least 20 cases per year. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of triple X using fetal cells obtained by endocervical lavage

Prenatal diagnosis of aneuploidies currently relies on invasive procedures such as chorionic villous sampling and amniocentesis. These methods can provide an accurate diagnosis of the fetal karyotype but are relatively invasive. Here, we report a case of the prenatal detection of triple X using fetal cells obtained by lavage of the endocervical canal prior to amniocentesis, following ultrasound diagnosis of hydrops fetalis. Copyright © 2003 John Wiley & Sons, Ltd.     

The making of fetal surgery

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd.