Dear Colleagues
Hello
At the outset ,I request you earnestly to help me to become the vice president of our esteemed socitiey FOGSI.
In this newsletter I am putting two of my cases of prenatal diagnosis,one is for beta thalassemia and other is sickle cell. Both are autosomal recessive disorders and can be prevented by doing prenatal diagnosis,either Chorion villus sampling at 10-12 weeks or by amniocentesis before 16 weeks. In these cases the mutations are usually known and the termination can be offered in affected pregnancy.
I am also putting up two controversial issues.
One is
Should we do day 3 or day5 embryo transfers.
And the other,which is of a very strong implications in society. It is regarding the abnormalities in children born from assisted reproductive technology. Previously it was reported in some studies to be around 11%. But in new study done in France ,it is found to be around 4 %, still significantly higher than the children born from natural pregnancies, which is around 1-2 % of all birth.
But US researcher came with another view point. They are in a view that ,we should not get too much alarmed by these findings. We have to look at various factors before coming to any conclusion, like multiple pregnancies ,prematurity and low birth weight in IVF children.
It is found that IVF children born through surrogates are of same incidence of birth defects as that of natural population, Hence ,it has to be thought that :Are the infertile women themselves at more risk because of their reasons of infertility or the procedures is to be blamed overall( like in-vitro culture of the embryos).
HEFA and Infertility network came out with some recommendations regarding this and I am putting them at the end.
With best wishes
Dr.D’Pankar Banerji
1. Prenatal diagnosis done for two cases
Beta thalassemia and sickle cell diseases are disorders of beta globin chain, an important component of hemoglobin. Both are autosomal recessive disorders.
An autosomal disordars and traits are ony manifrest when the mutant allele is present om a double dose ,like homozygosity. Individuals heterozygous for a recessive mutant alles ahow no features of the disorder and are perfectly healthy,i.e. they are carriers. The family tree for recessive traits differs considerably from that found in autosomal dominant traits. It is not possible to trace an autosomal recessive trait or disorder through the family,i.e. all the affected individuals in a family are usually in single sibship, that is they are brothers and sisters. This is sometimes referred to as “horizontal transmission”
There are three features which suggest the possibility of autosomal recessive inheritance. The first is that the disorder affects males and females in equal proportions. The second is that it usually only affects individuals in one generation in a single sibship, i.e. brothers and sisters,and does not occur in previous and subsequent generations. Lastly ,consanguinity in the parents provides further support for autosomal recessive inheritance.
Case no 1 :
Parents come to us had a child suffer from beta thalassemia major and died at an age 4yrs. Female partner is 28 yrs old and carrying a 13 weeks pregnancy. They approach us for prenatal diagnosis of the fetus ,whether it is also a sufferer or not.
We collected 5 ml blood samples of both the partners in EDTA. ( it is preferred to collect the blood sample of the affected child also ,if alive)
We did ultrasound guided chorion villus sampling with aseptic precaustions. CVS was done through vaginal route. The sample was collected in sterile culture media. Unfortunately the samples were not enough and maternal comtamination, and rejected by lab ( even though we saw the sample under stereozoom microscope ).
As it took 15 days by the lab before saying the sample is contaminated by maternal cells, the pregnancy advanced to 15 weeks . We repeated the CVS through abdominal route as placenta was not accessible by vaginal route( our preferred route). At the same time we did the amniocentesis.
Amniocentesis was done under sonography guide. The rule of 1 ml /week is followed and 12 ml of the fluid was withdrawn. First 1 ml was thrown away and rest was collected in a separate syringe and sent to lab.
The DNA report came as
Father’s mutaton: IVS1-5
Mother’s mutation: IVS1-5
Fetal DNA: Positive for IVS1-5,positive for normal sequence at IVS1-5,the fetus is a beta thalassemia carrier. Fetus has only one abnormal beta globin gene and not likely to suffer from disease
Case no 2 :
Couple came to us with a girl child of 6 yrs ,alive suffering from sickle cell major. The lady is carrying a pregnancy of 15 weeks.
We did amniocentesis with aseptic precautions and sent the sample to lab.
The report is carrier.
In both the cases ,the fetus is a carrier and child will have a natural and normal life ( ? to a great extent),and the couples are reassured that report is 98 percent correct and she can continue the pregnancy.
2. Day-3 or Day-5 embryo transfer : How to decide?
The decision to transfer embryos on day -3 or day -5 is one that requires careful thought. In general ,embryos that have formed blastocysts have a better chance of implanting successfully. Unfortunately ,not all embryos will progress to the blastocyst stage outside the body. This inconsistency raises the question as to whether the embryos that fail to from a blastocyst would have initiated pregnancy had they been transferred back into the uterus on day 3. Some studies have, indeed, demonstrated acceptable pregnancy rates with day-3 transfer of embryos that were of marginal quality and that. Based on historical data, would have been unlikely to form blastocyst in culture. Clearly ,the pregnancy rate in the absence of an embryos transfer will be zero, whereas even embryos of borderline quality , if transferred on day -3 , may potentially lead to pregnancy.
So how can we decide between a day -3 and a day-5 embryo transfer? Many clinics make the decision on day -3. If a patient has a certain number of high-quality embryos on day-3, then the embryos are maintained in culture for 2 additional days to allow for further embryo selection at the time of transfer. If the embryos fail to progress to the blastocyst stage, however, then there is no transfer-which often results in profound patient disappointment. If a limited number of embryos are available in day-3 and no embryos selection is needed, then the benefit of day -5 embryo transfer may be limited
One additional risk of a day-5 transfer is an increased rate of identical twinning( recently we have three consecutive cases). Carrying identical twin ( monozygotic twins) is considered to be a higher risk pregnancy than carrying a fraternal twins ( dizygotic twins). Identical twins often share a placenta (monochorionic twins) or may even be located within the same pregnancy sac (monoamniotic twins); both of these conditions are associated with increased rates of pregnancy complications.
3. IVF children are at increased risk of congenital anomalies ??
Assisted reproduction could lead to increased risks of congenital malformations, say scientists
The risk of congenital malformations is increased in children born through assisted reproductive technology (ART), such as IVF (in vitro fertilisation)or ICSI (intracytoplasmic sperm injection), researchers report at the annual conference of the European Society of Human Genetics.
In the largest study to date, researchers in France surveyed parents and paediatricians from 33 ART-registered clinics - approximately one third of the registered centres in France. Every ART birth from these clinics, from 2003 to 2007, was included in the study - a total of 15,162 births. Data was compared with information from national birth registers.
Lead researcher Dr Christine Viot said: 'We found a major congenital malformation in 4.24 per cent of the children…compared with the two to three per cent that we had expected from previous published studies. This higher rate was due in part to an excess of heart diseases and malformations of the urogenital system. This was much more common in boys. Among the minor malformations, we found a five times higher rate of angioma, benign tumours made up of small blood vessels on or near the surface of the skin. These occurred more than twice as frequently in girls than boys'.
IVF Does Not Significantly Increase Risk for Major Birth Defects
Slightly more than 4% of babies born via assisted reproductive technology such as in vitro fertilization (IVF) may have major birth defects, such as heart and urogenital tract malformations, according to a new study.
But U.S. experts are quick to point out that these risks are not much different from what would be expected in the general population. And the risks are much lower than what has been found in some other studies of babies born as a result of fertility treatments. The new research is slated to be presented at the annual meeting of the European Society of Human Genetics in Gothenburg, Sweden.
The major birth defects seen in babies born via IVF and/or ICSI included heart defects and malformations of the urogenital tract, such as hypospadias (an abnormality in the position of the opening of the urethra in boys). In the study, 110 children had genetic disorders, including six children with Beckwith-Weidemann syndrome, which is marked by body overgrowth, and may increase risk of certain cancers. Five children also had bilateral retinoblastoma (cancer of the eye’s retina).
Children born via assisted reproductive technology had a five times higher rate for minor birth defects such as angiomas (a benign tumor of small blood vessels causing a red growth on the skin). Angiomas were twice as common in girls as in boys, the study found.
It is not fully understood whether these birth defects or genetic diseases are caused by the infertility treatment itself or the underlying reason for infertility. Follow-up studies are planned, the researchers say.
Major malformations were more common among children born at low birth weights, but not those born prematurely, the study showed. Parental age at conception did not influence the rate of birth defects.
“. Imprinting disorders occur because of a mutation in a gene inherited from either the mother or the father.
Low Overall Risk of Birth Defects With IVF
Zev Rosenwaks, MD, the director of Perelman/Cohen Center for Reproductive Medicine at New York-Presbyterian/Weill Cornell Medical Center in New York, tells that more information is needed before any conclusions can be drawn about risks associated with assisted reproductive technology.
The rate of multiple pregnancies is often higher in children born after fertility treatment, he says. “Multiples have higher rates of abnormalities, and this may have affected the findings,” he says.
Counseling about possible risks associated with fertility treatment and informed consent are an important part of the fertility treatment process..
Not all birth defects are considered serious,.
“Angioma is a minor abnormality that can disappear..
“Even in the worst case scenario, the risk [of birth defects] is low,” says Jamie Grifo, MD, PhD, program director of New YorkUniversityFertilityCenter in New York City. “Your risk may be higher because you are infertile or because you are being treated for infertility, but it is still a low number,”
. There are millions of babies and millions of parents who would not be parents if not for reproductive technology."
It is not clear what factors are contributing to the higher risk of malformation in ART births. We need more research in order to understand the relationship between embryo culture media, timing of embryo transfer, the effects of ovarian stimulation, the use of ICSI, freezing of gametes and embryos, and these disorders.
The Human Fertilisation and Embryology Authority (HFEA) has issued a statement regarding the study, saying that 'the risks are still very small [but] it is important that patients are informed about this but not alarmed by it'. They added that 'where it suggests there may be a greater risk we share this information with patients in a clear way to help them understand the risks associated with the choices they are making'.
Infertility Network UK have also issued a statement: 'As with all medical procedures, patients need to be informed about all aspects of the treatment including possible risks to them, or in the case of assisted conception, the potential child. Patients who have any concerns should contact their clinician in the first instance to discuss them'.
An Appeal :
Please vote for me for the post of Vice President FOGSI
Dr.D’Pankar Banerji
