The status of fetoscopy and fetal tissue sampling. The results of the first meeting of the International Fetoscopy Group.
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It is the aim of fetoscopy to recognise or exclude malformations which are visible in the fetal stage and which are not associated with chromosomal damage. The requisite endoscope can be inserted practically without any problems into the amniotic cavity under local anaesthesia and in the manner of an "extended amniocentesis". If pregnancy is continued, the risk involed in fetoscopy must be assessed as similarly low as that of simple aminocentesis, as the clinical experience collected so far has shown. The clinical use of fetoscopy requires close co-operation with the geneticist and the parents concerned. The decision that fetoscopy is indicated lies mainly with the geneticist on account of the required expert genetic knowledge. Fetoscopy appears justified if there is an increased risk of malformation of the fetus which is manifest in the foetal stage and which is sufficiently serious to initiate therapeutic abortion if necessary, and, furthermore, if the risk involved in fetoscopy is in reasonable proportion to the risk of teh malformation. Over and above this, fetoscopy can also be justified if it is necessary to obtain fetal blood for examination. Satisfactory technical and endoscopic experience is the most important prerequisite for success and for reduced risk. Up to now, indication of fetoscopy was exclusively coupled to existing pregnancy and enhanced genetic risk. On the other hand, the question whether pregnancy should be permitted despite a known risk, simply because subsequent fetoscopy is envisaged, should be treated with reserve.
From December 1975 to July 1979 28 fetoscopies were made in the I. UFK Munich, 25 in local anaesthesia and under ultrasonic control using the real time scanner. 20 fetoscopies were made up to the 24th week of pregnancy, preceding an interruptio for medical or genetic reasons. 8 fetoscopies were made between the 26th and 38th week of pregnancy for diagnostic reasons. The best results were obtained before the 20th week of pregnancy, following a special fetoscopy score, developed by us. In consideration of the present state of the art, fetoscopy cannot be recommended as a clinical routine method for diagnosing external malformations. An application of substances directly into the fetal blood circulation by fetoscopy methods is not yet possible. Up to the 24th week of pregnancy fetoscopy methods can be used in specialised centres after properly weighing the risks, for the purpose of fetal blood sampling from the vessels of the chorionicplate or from umbilical vessels near the insertion of the chord to the placenta, for diagnosing genetical enzyme defects.
A fetoscope with a trocar of an external diameter of 3.9 and internal diameter of 2.9 mm was used. The optical equipment of the fetoscope had lenses with external diameters of 2.2 and 2.7 mm. The fetoscope can be inserted into the uterine cavity through the abdominal wall with local anaesthesia and insertion controlled by ultrasound. This type of insertion is uncomplicated and relatively free of risks. Thus an essential prerequisite for a successful fetoscopy is fulfilled. For the success of the fetoscopy, it is important to know what the diagnostic value of the procedure is and what can be seen through the fetoscope. The direct intrauterine visualization of the fetus or parts of the fetus is with the fetoscope under evaluation possible and was successful in 23 of 26 fetuses. The field of visualization is limited to 50 degrees by the optical system and only small parts of the fetus can be seen at a time. The extent of visualization of the fetus depends besides the optical system, on the quality of the amniotic fluid and the optimal timing of the fetoscopy in the second trimester between 15 and 18 weeks. Success is also dependant on the endoscopic experience and the technical training of the observer. After 13 of 26 fetoscopies the improvement was approximately 70%. Inspection of some parts of the fetus, for intance, the face is successful in every detail but still more or less fortuitous. Fetoscopy can only be deemed to be successful when a more or less total visualization of the fetus has heen accomplished. This was the case in 39% of the cases. Fetoscopy was used for diagnostic purpose in one case with the term delivery of a healthy infant. Fetal blood sampling by puncture of placental vessels under visualization is in its infancy. Fetoscopy is a justified procedure at this time in cases with a high genetic risk and for the avoidance of an abruptio.
Twenty woman at risk of carrying a fetus with homozygous beta-thalassemia who underwent fetoscopy and a matched control group of pregnant women were administered the Symptom Questionnaire to evaluate changes in distress. Women who were offered fetoscopy had significantly more anxiety, depression, somatic symptoms and hostility than the control group. Psychological distress significantly decreased after the results of fetoscopy were communicated to the patient, and the decrease was similar in normal control women. Five other patients had a diagnosis of homozygous beta-thalassaemia and their pregnancies were terminated. Their psychological distress increased when they learned the outcome of fetoscopy, but decreased again after termination. Psychological reactions to fetoscopy and amniocentesis appear to be similar, yet women who undergo fetoscopy suffer from more psychological distress.
A total of 105 fetoscopies were performed either prior to therapeutic abortions or, in 29 cases, for diagnostic purposes. In these latter cases the fetuses were at increased risk for congenital syndromes, limb deformities, cleft lip and palate or neural-tube defects. The procedure is performed transabdominally under local anaesthesia. The studies confirmed the practicability of the fetoscopic technique as described. Done under direct vision, using simultaneous real-time ultrasound-scanning, the fetoscope can be introduced without damage to fetus and placenta. In diagnostic cases, a total visualization of the entire fetus is not always necessary, as recognition and examination of specific fetal parts is often sufficient for prenatal diagnosis. Viewed in this way, the rate of diagnostic fetoscopies reached 78%. In these cases, the targets chosen for inspection could, in fact, be reached by the fetoscope. A total inspection of the fetus was aimed at in those fetoscopies performed prior to planned abortions in order to gain practice, and this was achieved in 42% of cases. In 5 of the 29 patients already mentioned, the pregnancy was terminated immediately after fetoscopy, and in 24 cases pregnancy was continued. Abortions have so far been recorded in 4 cases, not all of which were necessarily due to the fetoscopy, however. In general, fetoscopy appears to hold less danger for mother and child than had previously been anticipated.
OBJECTIVE: To develop a small animal model for fetoscopy. METHODS: In 12 time-dated pregnant rabbits at 22 days' gestational age (term 32 days) one amniotic sac in each uterine horn (n = 24) was used for a fetoscopic procedure. After laparotomy, a 2- to 3-mm microsurgical myometrial incision was made to expose the chorionic and amniotic membrane. Under microscopic control, a 2-mm needle was inserted into the amniotic sac. Through this a 1.2-mm endoscope was passed to carry out fetoscopy during maximally 10 min, using 5-10 ml saline amnioinfusion. Mean outcome measurements were ability to visualize the placenta, umbilical cord and the different fetal elements during fetoscopy, as well as fetal survival and weight at second-look operation at 30 days. The untreated amniotic sacs served as negative controls. RESULTS: In all cases, fetoscopy could be carried out successfully, and all fetuses survived till delivery without significant influence on fetal birth weight. CONCLUSION: The midgestational rabbit can be used to perform fetoscopy.
The fetal heart rate (FHR) was continuously monitored during 42 umbilical vessel punctures performed at the placental insertion of the cord in 24 diagnostic fetoscopies in which pure fetal blood was obtained. In only one patient did a deceleration first appear during puncture and aspiration of fetal blood. In two patients decelerations preceded fetoscopy and in two others they began during the fetoscopy but before puncture of an umbilical vessel. In 19 patients, the FHR did not change at all during the procedure. Fetal haemorrhage after sampling was either absent or minimal. Six pregnancies were terminated because a positive diagnosis had been made and 18 healthy babies were born. Umbilical cords were examined after 7 terminations of pregnancy and after 6 deliveries. In the former group the puncture could just be seen with the naked eye and the needle track was demonstrated histologically in 6. No traces of the puncture or other abnormalities were found in the cords after delivery. Fetal blood sampling from umbilical cord vessels, particularly at the placental insertion of the cord, is the technique of choice since pure fetal blood can be obtained without increasing the risk of fetoscopy.
Techniques for sampling pure fetal blood, fetal skin and for fetal examination by fetoscopy are described in detail after experience gained in 151 diagnostic fetoscopies on 145 patients. Of particular importance were a real-time scanner and a particle size analyser. The region of insertion of the umbilical cord into the placenta was the optimum site for obtaining pure fetal blood, and this was achieved in 136 out of 143 patients (95 per cent) sampled at 18 to 23 weeks gestation. This made maternal blood transfusion before prenatal diagnosis of haemoglobinopathies unnecessary. An anterior placenta rarely prevented successful fetoscopy, and often made fetal blood sampling easier. Four fetal losses (3.7 per cent) were judged to be due to fetoscopy.
The concentration of 13,14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM) was measured by radioimmunoassay in peripheral plasma in 62 pregnant women undergoing diagnostic fetoscopy. The mean concentration of PGFM before fetoscopy was 410.1 +/- 115.8 pmol/l (mean +/- S.D.) and the corresponding values at 10 and 20 min following the procedure were 440.9 +/- 125.6 and 394.4 +/- 103.3 pmol/l respectively; these differences were not statistically significant. Neither was there a significant change in the pre-fetoscopy concentration of PGFM in relation to gestational age between the 14th and 23rd week of pregnancy.
Embryoscopy and fetoscopy are techniques that render the developing embryo/fetus and its environment accessible to the "outside" world, which includes diagnosis and, potentially, therapy. Embryocopy and fetoscopy, sometimes referred to as embryofetoscopy, uses high-resolution fiber optic equipment for direct visualization of the embryo/fetus. This has been used to identify developmental milestones from weeks 4 to 8 after conception. With this technique, it has been possible to identify anomalies and confirm those previously diagnosed by ultrasound. Its application has generally included the first and early second trimester of pregnancy for prenatal diagnosis in continuing pregnancies. In addition, fetal blood sampling has also been successfully performed experimentally with this technology, extending its potential applications into the realm of fetal therapy. Future applications for embryofetoscopy include therapeutic interventions such as gene or cell therapy at a time when the embryo is immunologically tolerant. This article focuses on the importance of embryoscopy and fetoscopy (embryofetoscopy) to perinatal medicine and its potential contributions to the concept of fetal therapy.
Fetoscopy has consolidated its position in fetal medicine, thanks to a combination of insight into the pathophysiology of selected conditions that are amenable to fetal surgery and the technical innovations in endoscopic equipment. In clinical practice, two types of fetoscopy can be discerned: Obstetrical Endoscopy and Endoscopic Fetal Surgery. The first involves surgical interventions on the placenta, umbilical cord and fetal membranes. Nd:YAG laser coagulation of placental vessels in case of feto-fetal transfusion syndrome and cord occlusion in monochorionic pregnancy are the most typical procedures. The second type addresses some rare fetal conditions requiring in utero surgery; most experience has been gathered with congenital diaphragmatic hernia. Endoscopic fetal surgery has a different historical and experimental background than obstetrical endoscopy, but they both share technical aspects as well as potential side effects. In this review, we aimed at bringing together currently available experience. We suggest that future developments of fetal endoscopic operations will involve a mixture of concepts from both fetoscopy types to reduce maternal invasiveness and complications, eventually improving acceptance by parents and doctors. We encourage the registration of all experience in a yet available open registry for prospective data collection, supported by the European Commission, with as primary target the assessment of maternal and fetal safety.
We describe a case in which telesurgical consultation from Tampa, Florida, USA was used to accomplish operative fetoscopy in Santiago, Chile for the treatment of a twin pregnancy involving an acardiac twin. The procedure was successful and a healthy infant was delivered at 37.5 weeks. Operative fetoscopy, a surgical approach to correct birth defects in utero via combined ultrasound and endoscopy, is only available in a handful of centers worldwide. Telesurgery makes use of telecommunication to allow a surgeon at a primary operating site to consult with another experienced surgeon for complex surgical cases. This case illustrates the potential for ultrasound and telesurgery to expand the horizons of operative fetoscopy.
The present article summarizes six years of experience with intrapartum visualization of the uterus and its contents (fetus, umbilical cord, placenta and amniotic fluid). The choledochofiberscope, previously sterilized in 96% alcohol was introduced into the amniotic cavity via the cervical canal after spontaneous or artificial rupture of the membranes. The following abnormalities were diagnosed with high accuracy: umbilical cord complications (28 cases), placental pathology (36 cases), dehiscence of the uterine scar (2 cases), fetal dysmaturity (19 cases), congenital anomalies (15 cases). No fetal or maternal complications of fetoscopy were noted. Intrapartum fetoscopy can provide the obstetrician with important information in selected cases. Potential uses of intrapartum fetoscopy are discussed.
The need for fetoscopy in prenatal diagnosis has been established and its value has been demonstrated. The number of cases for which this fetoscopy is necessary remains small. The less traumatic ultra-sound diagnosis more and more competes with endofetoscopic inspection. The fetoscopy is necessary for fetal tissue biopsy and fetal blood sampling. Progress in intra-uterine treatment can be expected.
A technique for fetal blood-sampling in the second trimester of pregnancy (between 16 and 22 weeks' gestation) combining fetoscopy with real-time ultrasound was used in 48 attempts at fetal blood-sampling. Specimens containing fetal red cells with or without amniotic fluid or maternal blood, and adequate for diagnosing haemoglobinopathies, were obtained in 45 of the 48 fetoscopies. Sampling was successful in all 18 patients with a posterior placenta, and in 27 of the 30 with an anterior placenta. In 22 of the last 27 consecutive fetoscopies pure fetal blood was taken; the placenta was anterior in 16 and posterior in six. Out of 17 cases sampled between 18 and 22 weeks' gestation pure fetal blood was obtained in 16. The volume of the samples varied from 50 to 500 microliter. The ability to obtain pure fetal blood consistently even when the placenta is anterior will increase knowledge of fetal physiology and the scope of prenatal diagnosis.
A brief report is given on fetal blood sampling by fetoscopy in three fetuses at risk for severe congenital bleeding disorder; hemophilia A in two cases, von Willebrand's disease in one. Published reports on complications of fetoscopy are reviewed. Out of all together about one hundred pregnancies that have been allowed to continue after fetoscopy, five ended in miscarriage. No other serious complication has been reported.
Induction of pneumoperitoneum, laparoscopy, and intrauterine endoscopy (fetoscopy) were successfully accompished in 23 pregnant sheep at 45 to 60 days' gestational age. The fetoscope, a conventional 2.7 mm. Hopkins straightforward wide-angle telescope (Stortz 27018A) encased in a prototype 3.1 mm. eccentric cannula, incorporates a 25 gauge needle channel. Multiple pregnancy was encountered in 11 animals. Forty-two separate fetoscopic trials were accomplished; a fetoplacental blood sample was obtained in 52 per cent of the trials. A mean interval of 19 +/- 9 days (+/- S.D., range 6 to 37 days) was allowed between fetoscopy trials. Fetal deaths occurred in nine animals (39 per cent). We believe that laparoscopy permits preselection of the proposed fetoscopy puncture site and will permit the operator to thereby avoid the placenta and/or uterine vessels.