Prenatal and preimplantation diagnosis 22.04.2021

Prenatal and preimplantation diagnosis 22.04.2021 for undergraduate medical students

1. PRENATAL DIAGNOSIS & PGD Dr. Shazia Iqbal  Assistant Professor (Obstetrics & Gynaecology) Director of Medical Education Unit Vision College of Medicine, Riyadh

2. OUTLINE Benefit. Techniques. Ultrasonography Amniocentesis Chorionic villus sampling Maternal serum beta-HCG preimplantation genetic diagnosis

3. BENEFIT Benefits Congenital abnormalities affect approximately 2% of newborn babies in the UK Account for around 21% of perinatal and infant deaths, as well as causing significant disability and morbidity later in life. There are a variety of non-invasive and invasive techniques available for prenatal diagnosis. Each of them can be applied only during specific time periods during the pregnancy for greatest utility.

4. THE TECHNIQUES EMPLOYED FOR PRENATAL DIAGNOSIS Ultrasonography Amniocentesis Chorionic villus sampling Fetal blood cells in maternal blood Maternal serum alpha-fetoprotein Maternal serum beta-HCG Maternal serum unconjugated estriol

5. ULTRASONOGRAPHY This is a non-invasive procedure that is harmless to both the fetus and the mother. High frequency sound waves are utilized to produce visible images from the pattern of the echos made by different tissues and organs, including the baby in the amniotic cavity. Recognition of the major internal organs and extremities to determine if any are abnormal can best be accomplished between 16 to 20 weeks gestation.

6. AMNIOCENTESIS This is an invasive procedure in which a needle is passed through the mother's lower abdomen into the amniotic cavity inside the uterus. Enough amniotic fluid is present for this to be accomplished starting about 14 weeks gestation. For prenatal diagnosis, most amniocenteses are performed between 14 and 20 weeks gestation. In the third trimester of pregnancy, the amniotic fluid can be analyzed for determination of fetal lung maturity. This is important when the fetus is below 35 to 36 weeks gestation, because the lungs may not be mature enough to sustain life following birth. Risks with amniocentesis are uncommon. Bleeding, cramping, and leaking fluid from the vagina Infection

7. CHORIONIC VILLUS SAMPLING (CVS) In this procedure, a catheter is passed via the vagina through the cervix and into the uterus to the developing placenta under ultrasound guidance. An alternative approach is transabdominal. The introduction of the catheter allows sampling of cells from the placental chorionic villi. These cells can then be analyzed by a variety of techniques. The most common test employed on cells obtained by CVS is chromosome analysis to determine the karyotype of the fetus. The cells can also be grown in culture for biochemical or molecular biologic analysis. CVS can be safely performed between 9.5 and 12.5 weeks gestation. Risks of the procedure Miscarriage Preterm labor

8. CHORIONIC VILLUS SAMPLING (CVS)

9. MATERNAL SERUM BETA-HCG This test is most commonly used as a test for pregnancy. Beginning about a week following conception and implantation of the developing embryo into the uterus, by the time the first menstrual period is missed, the beta-HCG will virtually always be elevated enough in maternal urine to provide a positive pregnancy test. The beta-HCG can also be quantified in serum from maternal blood, and this can be useful early in pregnancy when threatened abortion or ectopic pregnancy is suspected, because the amount of beta-HCG will be lower than expected. Later in pregnancy, in the middle to late second trimester, the beta-HCG can be used in conjunction with the MSAFP to screen for chromosomal abnormalities, and Down syndrome in particular. An elevated beta-HCG coupled with a decreased MSAFP suggests Down syndrome. Very high levels of HCG suggest trophoblastic disease (molar pregnancy).

10. PREIMPLANTATION GENETIC DIAGNOSIS

11. WHAT IS PGD The procedure which involves the removal of one or more blastomeres to test for mutations in a specific gene sequence or chromosomal abnomlalities before transferring

12. PGD INDICATIONS An altemative to conventional PND for couples with a significant risk of transmitting a serious genetic disorder to their offspring Avoiding abortion ( enomaous physical and psycological burden) Presence of ethical concems in aborting embryoes affcted with specific disorders ( for example: hearing oss , skeletal disorders, . . .)

13. CLINICAL APPLICATIONS Carriers ofmutations (Autosomal dominant disorders, Autosomal recessive disorders) Female carriers of X- linked disorders HLA matching Carriers ofa balanced chromosomal trans[ ocation , inversion or other structural rearrangements

14. PGD PROCEDURE Stimulation : controlled ovarian stimulation Retrieval : oocyte retrieval Fertilization : fertilization (standard IVF/ICSI)

15. BIOPSY METHODS In looking at the entire set of data, the most common method of zona breaching used was laser drilling 58% cleavage stage biopsy has predominated data collections I X.

16. WHY IS PGD NECESSARY the aim of PGD is to prevent transmitting genetic disorder to offspring Theses could include: Cystic Fibrosis (affects the lungs pancreas liver and intestine) Triploidy ((three) copies of each chromosome) Thalassemia (causes weakening and destruction of red blood cells Duchenne Muscular Dystrophy (causes muscle degeneration

17. HOW IS PGD PERFORMED During the PGD procedure in vitro embryos are screened for genetic defects. only the healthy embryos that are considered condition free are transferred for implantation

18. HOW IS PGD PERFORMED the procedure of PGD begins with IVF treatment later followed by genetic screening: 1- During IVF eggs are harvested and fertilised by sperm in the laboratory to form zygotes 2- the zygotes continue developing in the lab for about 3 days until they typically reach the 8 cell stage 3- at this known as embryo biopsy is performed where an embryo’s cell is extracted 4- the cell undergoes genetic screening where is analysed

19. How safe is PGD The PGD treatment it self is thought to be very safe- there is no evidence that babies born following PGD suffer any more health or developmental problems than babies born using IVF alone. there are risk from having IVf though

20. Why might PGD be unsuccessful Unfortunately sometimes there are embryo suitable for transfer to the womb this could be because: Not enough eggs are produced or fertilised in the first place Removing the cell for analyses damages the embryos are affected by the genetic disease

21. REFERENCE https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/chorionic-villus-sampling-cvs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548328/ https://webpath.med.utah.edu/TUTORIAL/PRENATAL/PRENATAL.html

22. THANK YOU