Multiple Pregnancy after ART: The Importance of an Early Diagnosis

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Dr. Hugo Verhoeven:  “My name is Hugo Verhoeven, I’m from the Center for Reproductive Medicine in Dusseldorf, Germany, and I’m reporting from the European Congress on Perinatal Medicine in Porto.  It is an exceptional honor for me talking now with Dr. Alexandra Matias who is a Specialist in Obstetrics and Gynecology at S. Joao Hospital in Porto and also Assistant Professor at the Faculty of Medicine at the University of Porto.  Dr. Matias, thank you very much for giving me the chance to talk to you.  Yesterday, I heard two of your lectures and I have the feeling that you are one of the coming stars in the field of obstetrical problems of multiples.  Yesterday, we discussed the worldwide exploding incidence of multiples. One major reason for that is that artificial reproductive technologies are increasingly successful so that in the last ten years we see, an explosion, especially in the number of triplets and higher order multiples. You stressed that it’s very important to diagnose a multiple pregnancy as early as possible, to start your special type of screening for multiples in order to counsel as early as possible those couples expecting a multiple pregnancy. So when do you advise to perform the first ultrasound, and what are you evaluating at that moment?”

Dr. Alexandra Matias:  “Whenever there is a discrepancy between the gestational age estimated by the last menses period and fundal height, when two differently located fetal heart sounds are detected, or when hCG plasma levels are higher than expected, an ultrasound examination is mandatory as early as possible.  The 10-14 weeks’ scan is the best targeted ultrasound because in this scan there are several questions that can be promptly answered; the first is the number of embryos or fetuses and the chorionicity.”

Dr. Hugo Verhoeven:  “What is chorionicity?”

Dr. Alexandra Matias:  “Chorionicity stands for the type of placentation and this is a very important issue because chorionicity is a significant factor, that will influence the perinatal course. The reality of expecting two babies with two placentas or two babies with one placenta is completely different, involving specific medical problems in the future. This information about the type of placentation is very important for the doctor in charge of a pregnant woman carrying multiples to know what kind of pregnancy he is dealing with.  So it’s mandatory to define the number of embryos/fetuses and chorionicity.  Secondly, it’s very important to assess the gestational age: sometimes the ladies aren’t sure about the last menstrual period, they have been taking the pill for the last three months, contributing to an unreliable gestational age.  Therefore, it is of paramount importance to assess the correct gestational age, to know exactly how many weeks we’ll have at the end when we want to terminate a pregnancy or when the delivery will spontaneously occur.  Another important issue, not only concerning singletons but also multiples, is the screening of aneuploidies.”

Dr. Hugo Verhoeven:  “What is that?”

Dr. Alexandra Matias:  “Aneuploidies are chromosomal abnormalities. The most frequent aneuploidy is Down’s syndrome or mongolism. When the karyotype of a fetus is abnormal, the parents should be informed in order to decide what to do with this pregnancy. One of the possibilities for assessing this risk is to measure nuchal translucency. Nuchal translucency is the fluid that accumulates behind the fetal neck and which thickness is measured by ultrasound between ten and fourteen weeks gestation.  In the case of a monochorionic twin pregnancy, nuchal translucency can be also used for screening of an early onset hemodynamic overload. If nuchal translucency is increased in one of the fetuses and discrepant between the two, this can be the first sign of hemodynamic imbalance that will later be translated as a twin-to-twin transfusion syndrome.  The donor will transfuse blood to the recipient and this “flood” will have consequences - cardiac consequences, neurological consequences. Therefore in order to avoid such sequelae  it is of importance to screen for this hemodynamic problem.  Summing up, I think it’s very important in multiples to perform a scan between 10-14 week gestation in order to assess the gestational age, to define chorionicity and the number of fetuses involved, to screen for aneuploidies, and in the case of monochorionic twin pregnancies, to have a first clue about the hemodynamic behavior of those fetuses early in pregnancy.”

Dr. Hugo Verhoeven:  “This brings us immediately to the next very important thing.  If you have the suspicion that something’s going wrong and you think there could be a chromosomal anomaly or you have a suspicion there is the beginning of a transfusion syndrome between the two babies, what do you do?”

Dr. Alexandra Matias:  “In the first case if an abnormal karyotype is suspected, of course, we should inform the couple that after a positive screening test the only possibility of being sure about the karyotype is to perform a diagnostic test, that is, an invasive procedure must be done.  Depending on the experience of the centers around the world on what is routinely performed in each hospital (either amniocentesis or chorionic villus sampling, by the transvaginal and transabdominal approach), and the time needed for a confident answer from the cytogenetic lab, the appropriate invasive test will be selected to obtain the karyotype as soon as possible.

Dr. Hugo Verhoeven:  “So the difference between the two is that you can take a little part of the placenta to do an analysis or you’re taking out a little bit of amniotic fluid. What about difficulties in performing amniocentesis , singletons compared with quintiplets ?

Dr. Alexandra Matias:  “Clearly to perform an amniocentesis in a singleton pregnancy is a much more straightforward procedure. To accomplish it in multiples is much more complicated.  Highly skilled operators are needed. The decision of which one of the invasive procedures should be chosen in the case of multiples depends mostly on the type of chorionicity, on the experience and technical skills of the center, on the gestational age, on the position of the fetuses. The risks inherent to invasive tests such as fetal demise or premature delivery are less than 1% in experienced hands – the risks for both singletons and multiples are about the same.”

Dr. Hugo Verhoeven:  “How do you know that each time you’re in another sac and that you’re not aspirating the same sac two or three times so that you are maybe missing one of the sacs which has the chromosomal anomaly? 

Dr. Alexandra Matias:  “The risk of sampling twice the same fetus and of not having information about the other fetus exists but there are some tricks to identify each of the sacs. One of them would be to use dyes like indigo carmine. Another technique is to use bubbles exiting the needle to assess in which of the sacs the operator is in. Another possibility is the “one-shot” technique where the fluid is aspirated from the closest sac and then the syringe is advanced to sample the most distant sac. If the two gestational sacs are clearly differently located, for example one on the right side and one on the left side of uterus, one can go first to one sac and then to the opposite side to sample the other sac.  So there are different techniques but, unfortunately, we cannot be absolutely sure that we have sampled each sac, each baby.”

Dr. Hugo Verhoeven:  “We do an aspiration of amniotic fluid and find a chromosomal anomaly, we have to do something. We have quintuplets or triplets and one of the babies has a Down’s syndrome.  Tell me what can happen or what the treatment could be and what would be the consequence for the, let’s call them, the survivors, what is the risk for them?”

Dr. Alexandra Matias:  “Again, it depends on the legal policies of the country and on what the parents want to do about this pregnancy and about this baby.  Let’s say that they’d like to terminate this pregnancy and that the termination is allowed in their country.  Termination of pregnancy can be done with potassium chloride, for example, to stop the heart of the baby from beating. But before performing the procedure chorionicity must be known and checked.  If one is dealing with a dichorionic pregnancy, the termination of the affected twin will be harmless for the co-twin.  In the case of a monochorionic twin pregnancy, the demise of one of the twins can cause serious morbidity to the surviving co-twin due to the transfer through superficial anasthomoses of blood from the baby that is alive to the baby that was terminated. The survivor will exsanguinate to the dead fetus and neurological sequellae will eventually arise due to an abrupt hypotension. Polycystic encephalomalacia, porencephalic cysts and cerebral palsy in the survivor are some examples of the neurological impairment consequent to the intrauterine death of a co-twin.”

Dr. Hugo Verhoeven:  “So that would be the treatment of a medical situation; you have a malformation so you must do something.  Now we also have the problem of the elective reduction because the patient doesn’t want to have triplets or because you think that the lady is not able to carry triplets till the end of pregnancy because of medical reasons and so you have to do an elective reduction.  Do you have some special thoughts about that?”

Dr. Alexandra Matias:  “I think that in most instances the discussion about multiples should begin much earlier than elective termination. People dealing with iatrogenic multiples should think how many embryos could or should be transferred.  For example, I know from your talk f yesterday that cryopreserved fetuses tend to give less high order multiples. Considering that the transfer of two or three embryos will have approximately the same rate of success we should not transfer three but only two.  Of course, each case is a case. If the couple seeking an infertility consultation has a very long story of infertility and the mother is more than forty years old, the transfer of more than two embryos should be discussed with the couple. The higher rates of success associated with the transfer of more than three embryos should be coupled with clear information about the higher rates of premature delivery, very low birth weight infants, neurological sequellae, and that cerebral palsy, for example, is much more prevalent among multiples than in singletons.  So I think that people involved in programs of infertility and with iatrogenic multiples should not transfer more than two embryos since it is clear that transferring three will not increase the success of this program.”

Dr. Hugo Verhoeven:  “But  let us say you already have the multiple, in the 10th week you find triplets, even if you did the transfer of only two embryos this can happen.  The patient says - I don’t want that, what is your policy?”

Dr. Alexandra Matias:  “In my country the reduction of multiples without major problems (lethal malformations or abnormal karyotype) is not allowed.  However, there are countries like the United States and Israel where elective termination of high order multiple pregnancies is safely undertaken until 16 weeks gestation with high rates of success.  After that period it can be very problematic because the risks of premature delivery increase exponentially and because for the parents, I think, the bereavement is worse.  So the best experience is to terminate these high order multiple pregnancies until 16 weeks.”

Dr. Hugo Verhoeven:  “My final question is always the same - what do you expect from the future, what are your dreams, what do you expect bettering your professional life?”

Dr. Alexandra Matias:  “First of all, I would like to come back to the first point of our talk. We can deliver a better service to multiple gestation parents if we can offer an early scan at 10-14 weeks, so that the parents know what they can expect from this pregnancy – how many multiples are expected, what kind of multiples are coming, and what are the medical problems associated with this kind of twins.  Secondly, I think that the neonatologists have come to a plateau in the care they can offer to very low birth weight infants.  We have not made important steps forward in the last years and the limit of viability is still 24-25 weeks around the world. I think that if such panorama remains unchanged, we should continue to be very careful about high order multiple pregnancies due to the ongoing problems in dealing with severe prematurity.  This is really a very important point. If these babies are born prematurely, they’ll be more prone to future handicaps like cerebral palsy or lung hypoplasia, and they’ll be a major burden, familial burden, social burden, and psychological burden to this family and to the coexisting children.  I think that the ball is now in the field of obstetricians, since the neonatologists are already doing as much as they can.  So let’s know from the very beginning what kind of multiples are we expecting in order to offer the best of our services to multiple gestations.”

Dr. Hugo Verhoeven:  “Perfect, Alexandra, thank you very much.”

Dr. Alexandra Matias:  “It was my pleasure.”