diagnosis and tests of embryo and fetus : prenatal diagnosis

diagnosis and tests of embryo and fetus : prenatal diagnosis

1. JIMMA UNIVERSITY SCHOOL OF BIOMEDICAL SCIENCES DEPARTMENT OF ANATOMY EMBRYOLOGY ASSIGNMENT 1

2. Diagnosis And Test Of Embryo And Fetus By: Eyassu Kassahun(BSc. MSc student) Submitted to: Mr. Getachew C.(BSc. MSc. And PHD fellow) 2

3. Outline Objective Introduction Indication Importance Types Non Invasive methods Invasive Methods Ethical debate Summary reference 3

4. Objective Understand the definition of prenatal diagnosis. Identify the indications and importance of prenatal diagnosis. Differentiate between the types of prenatal diagnosis. Explain the different types of invasive prenatal diagnosis and non invasive prenatal diagnosis. Identify the ethical debate of preimplantation diagnosis 4

5. Introduction Prenatal tests/Diagnosis are medical tests pregnant women get during pregnancy. Procedures undertaken to diagnose genetic abnormalities and structural anomalies often on early embryo and fetus in order to undertake timely prenatal counseling and appropriate interventions. 5

6. Con’t Embryo testing and treatments can be used by people who have serious inherited diseases in their family and want to avoid passing the disease onto their children. There several approaches for assessing growth and development of the fetus in utero, including ultrasound, amniocentesis, chorionic villus sampling, and maternal serum screening. 6

7. Con’t In combination, these techniques are designed to detect malformations, genetic abnormalities, overall fetal growth, and complications of pregnancy, such as placental or uterine abnormalities. Their use and development of in utero therapies have heralded a new concept in which the fetus is now a patient . 7

8. Indications for prenatal diagnosis Advanced maternal age Previous child with a chromosome abnormality Women who are pregnant with multiples (twins or more) Family history of single gene disorder Family history of a neural tube defect 8

9. Con’t Family history of other congenital structural abnormalities Abnormalities identified in pregnancy Women who have previously had miscarriages Other high risk factors(consanguinity, Maternal illnesses) 9

10. Importance of Prenatal diagnosis Allows To identify structural, functional or chromosomal abnormalities. timely medical treatment of a condition before or after birth Parents to make decisions regarding whether to abort a fetus with diagnosed condition Parents to prepare psychologically, socially, financially and medically for a baby with a health problem or disability Determine the outcome of pregnancy 10

11. Types: Methods of prenatal diagnosis Invasive Amniocentesis Cordocentesis CVS Coelocentesis Non-invasive Ultrasonography MRI Cell-free fetal DNA Triple test 11

12. Invasive Vs Non-Invasive In non-invasive prenatal diagnosis t here is no need to take a sample from inside the uterus (in contrast with invasive prenatal diagnosis using amniotic fluid or chorionic villus sampling). This removes the small chance of miscarriage associated with invasive procedures. It can be performed from as early as eight to nine weeks’ gestation (dependent on the condition to be tested for). 12

13. ULTRASONOGRAPHY is a safe, commonly used, relatively accurate and non-invasive technique that uses high-frequency sound waves reflected from tissues to create images. It may be transabdominal or transvaginal , with the latter producing images with higher resolution. It has advanced to a degree where detection of blood flow in major vessels, movement of heart valves, and flow of fluid in the trachea and bronchi is possible. 13

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15. Important parameters revealed by ultrasound include: characteristics of fetal age and growth; presence or absence of congenital anomalies like anencephaly and spina bifida, omphalocele and gastroschisis , cleft lip and palate; status of the uterine environment, including the amount of amniotic fluid; placental position and umbilical blood flow; and whether multiple gestations are present Monitor needle or catheter insertion during amniocentesis and chorionic villus biopsy 15

16. Ultrasound may be used at: First trimester - to check the embryo is developing inside the womb (rather than inside a fallopian tube) confirm the number of embryos, calculate the gestational age and the baby’s due date. Second trimester - to check the development of fetal structures such as the spine, limbs, brain and internal organs. The size and location of the placenta is also checked. The baby’s sex can be established, if the parents wish to know. 16

17. Con’t Third trimester - to check the baby is continuing to grow at a normal rate. The location of the placenta is checked to make sure it isn’t blocking the cervix. There are no known risks, complications or side effects for either the mother or her unborn baby. 17

18. Limitations Small field of view, Limited soft-tissue acoustic contrast, Beam attenuation by adipose tissue, Poor image quality in oligohydramnios, and Limited visualization of the posterior fossa after 33 weeks' gestation because of calvarial calcification. 18

19. MRI: Magnetic Resonance Imaging MRI can supplement the information obtained from your high-resolution fetal ultrasound and can provide additional information regarding your baby’s diagnosis. It is performed in the 2nd or 3rd trimester of pregnancy. This type of examination is used to evaluate abnormalities in your baby's brain, spine, and body. Important advantages of magnetic resonance imaging are that it does not use ionizing radiation and that it has high soft-tissue contrast and resolution 19

20. Cell-free fetal DNA Screening as noninvasive prenatal testing (NIPT) with high sensitivity and specificity identifying DNA fragments that are derived primarily from apoptotic trophoblasts can be performed at any time later 9 to 10 weeks' gestation. Results are available in 7 to 10 days. he screening performance the pooled sensitivity to detect Down syndrome was 99 %, and for trisomies 18 and 13, 96 % and 91 % , respectively. 90 % with Turner syndrome (45,X) and 93 % with sex chromosome aneuploidies other than 45,X. 20

21. Cordocentesis Fetal blood samples may be obtained directly from the umbilical vein. It is used for the diagnosis of many fetal abnormal conditions, including aneuploidy, fetal growth restriction, fetal infection, and fetal anemia. is usually performed after 18 weeks of gestation under continuous direct ultrasound guidance, which is used to locate the umbilical cord and its vessels. 21

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23. Con’t It can obtain a sample of blood from a fetus’s umbilical cord to detect blood disorders, infections and genetic mutations. It also permits treating the fetus directly, including the transfusion of packed red blood cells for the management of fetal anemia or deliver medications. It’s also called percutaneous umbilical cord blood sampling (PUBS) or funipuncture . 23

24. What does cordocentesis test for? Blood disorders such as fetal hemolytic disease, when red blood cells break down quickly, Anemia , Thrombocytopenia . Chromosomal abnormalities (inherited or random genetic mutations), such as  Down syndrome . Infection, such as  toxoplasmosis  or  rubella . Isoimmunization, when a pregnant person’s blood isn’t compatible with the fetus’s. 24

25. AMNIOCENTESIS is the most common invasive prenatal diagnostic procedure, usually performed between 15 and 18(20) weeks gestation. Amniocentesis is a procedure in which amniotic fluid and fetal cells is removed from the uterus for testing or treatment. Approximately 20 to 30 ml of amniotic fluid is sampled by inserting a 22-gauge needle through the mother’s anterior abdominal and uterine walls into the amniotic cavity by piercing the chorion and amnion. 25

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27. Con’t Amniocentesis is a test used for prenatal diagnosis of inherited diseases, genital infections alloimmunization Rh incompatibility, neural tube defects, lung maturity. 27

28. Con’t Although amniocentesis does carry some significant risks , the medical community commonly accepts it as a safe and useful procedure. The amniocentesis procedure-related loss rate approximates 0. 1 to 0.3 percent when performed by an experienced provider about 1 per 500 procedures. 28

29. COMPLICATIONS A. Maternal Complications: 1. Infection, 2. Hemorrhage (placental or uterine injury), 3. Premature rupture of membranes and premature labor, 4. Maternal iso-immunization in Rh - negative mother. B. Fetal complications: 1. Trauma 2. Feto -maternal hemorrhage. 29

30. Coelocentesis Coelocentesis is an invasive technique that can provide prenatal diagnosis of disorders, from as early as 7 weeks' gestation. Fluid take from coelomic space b/n amniotic membrane and uterine cavity. The risk of fetal loss is 0 or less than that of aminocentesis . 30

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32. MATERNAL SERUM SCREENING Maternal serum screening provides a relatively non-invasive technique for an initial assessment of fetal well being. A search for biochemical markers of fetal status led to development of maternal serum screening tests. AFP is produced normally by the fetal liver, peeks at approximately 14 weeks, and “leaks” into the maternal circulation via the placenta. Thus, AFP concentrations increase in maternal serum during the second trimester and then begin a steady decline after 30 weeks of gestation. 32

33. In cases of neural tube defects and several other abnormalities, including omphalocele, gastroschisis and others, AFP levels increase in amniotic fluid and maternal serum. In other instances, AFP concentrations decrease as, for example, in Down syndrome, trisomy 18, and sex chromosome abnormalities. These conditions are also associated with lower serum concentrations of human chorionic gonadotropin ( hCG ) and unconjugated estriol Alpha-fetoprotein(AFP), human chorionic gonadotropin(HCG) and unconjugated estriol(UE3) are called Triple Tests. 33

34. Alpha-Fetoprotein Assay An AFP test is a test that is mainly used to measure the level of alpha-fetoprotein (AFP) in the blood of a pregnant women. Alpha-fetoprotein (AFP) is a glycoprotein that is synthesized in the fetal liver, umbilical vesicle, and gut. AFP is found in high concentration in fetal serum, peaking 14 weeks after the LNMP. Small amounts of AFP normally enter the amniotic fluid. 34

35. An AFP test is usually done between 15 and 20 weeks of pregnancy. During pregnancy, if your AFP blood levels are higher or lower than normal, it may be sign that: The baby has a high risk of having a genetic disorder like  neural tube defect and down syndrome. Your estimated due date is wrong. You're pregnant with more than one baby. 35

36. Chorionic Villus Sampling It involves inserting a needle transabdominally or transcervical into the placental mass and aspirating approximately 5 to 30 mg of trophoblastic tissue. Biopsy of chorionic villi is typically performed between 10 and 13 weeks' gestation. Advantage : results are available earlier in pregnancy, permitting more time for decision-making. 36

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38. Indications Previously affected child or a family history of a genetic disease, chromosomal abnormalities, or metabolic disorder Maternal age over 35 years by the pregnancy due date Risk of a sex-linked genetic disease Previous ultrasound with questionable or abnormal findings Abnormal cell-free DNA test 38

39. Used to detect chromosomal abnormalities, inborn errors of metabolism, X-linked disorders. The rate of fetal loss is approximately 1%, slightly more than the risk from amniocentesis. 39

40. Applications of prenatal diagnosis Maternal serum screening:- Fetoprotein, estriol and HCG estimation Ultrasonography:- Structural abnormalities Amniocentesis:- Fetoprotein and acetylcholinesterase Chromosomal analysis Biochemical analysis Chorionic villus sampling:- DNA analysis Chromosomal analysis Biochemical analysis Fetal blood sampling:- Chromosomal analysis DNA analysis 40

41. Debate: Preimplantation Genetic Testing During the process of IVF, Testing involves removing one or a few cells from the embryo, and analyzing the DNA. After testing, the healthiest embryos can be selected, greatly improving the couple's chances of having a healthy baby. The advantage of testing embryos before they are implanted is that only the ones that are free of harmful genetic conditions are allowed to develop. 41

42. Con’t Two main sets of ethical objections make PGD and proposals for its extension controversial. One set of objections arises from the need to create and then select embryos on chromosomal or genetic grounds, with the deselected embryos then usually discarded . Other objections concern the fact of selection itself. 42

43. Summary: key takeaways Prenatal tests/Diagnosis are medical tests pregnant women get during pregnancy undertaken to diagnose genetic abnormalities and structural anomalies. There are invasive and non invasive types of prenatal diagnosis with the latter having no or less risk on the mother and fetus Ultrasonography is a safe, commonly used, relatively accurate and non-invasive technique 43

44. Amniocentesis is the most common invasive prenatal diagnostic procedure, usually performed between 15 and 18(20) weeks gestation. Preimplantation Genetic Testing raises ethical objections. 44

45. Any Questions? 45

46. Reference Langman’s medical embryology, 8 th edition , T.W. Sadler. The developing human, clinically oriented embryology, 9 th edition, Keith L. Moore, T.V.N Persaud, Mark G. Torchia, 2013 BRS Embryology, 5 th edition Ronald W. Dudek, 2011 William’s Obstatrics , 25 th edition, F. Gary Cunningham Kenneth J. Leveno Steven L. Bloom Jodi S. Dashe Barbara L. Hofman Brian M. Casey Catherine Y. Spong , 2018 46

47. Thank you For your attention 47