Reproductive Technology

1. Reproductive Technology

2. Learning Objectives By the end of this class you should understand: • Causes of infertility in men and women • The different types of assisted reproductive technologies • The primary sources of ethical issues surrounding ART • The technique and concerns for genetic screening • The potential for treatments such as gene therapy and cord blood • The process and benefits of genetic counseling

3. Fertility • Not all people are naturally able to produce children • Infertility is approximately equally common in men and women • Increases with age in women

4. Types of Infertility • Primary infertility is inability to have a first child • Secondary infertility is when a couple has already had one or more children but is having difficulty having more • Focus is on primary infertility here

5. Female Infertility Causes • Problems with hormonal levels • Since hormones are required for ovulation • Ovarian problems • Since ovaries produce eggs • Oviduct/Uterine problems • Since this is where the fetus is fertilized/grown

6. Female Infertility

7. Male Infertility Causes • Low sperm count • Fewer sperm than typical • Low sperm motility • May be partially genetic in origin • Genetic infertility • Mutations on Y chromosome in particular • No sperm produced • Kilefelter's syndrome, infection, damage to testes, hormonal imbalance including steroids, etc

8. Male Infertility

9. Assisted Reproductive Technologies • Refers to all techniques to improve fertility • Primary techniques include artificial insemination and in vitro fertilization • The exact choice depends on which parent has the problem and what kind

10. Artificial Insemination • Artificial Insemination uses some means of artificially creating a fertilization event • Only viable if the mother's uterus is healthy • Major use is when father is infertile or mother wants to become a single parent • May also be applied after IVF

11. In Vitro Fertilization • Creation of a fertilization event outside a person's body • “In vitro” means “In glass” referring to a test tube • May apply when female is infertile or male sperm has motility problems • Must be implanted into healthy uterus, either the mother's or a surrogate

12. Sperm Injection • A particular type of in vitro fertilization is called intracytoplasmic sperm injection • Performed by injecting a single sperm cell directly into an egg • Typically for sperm count or motility problems • Egg is then implanted as normal

13. Egg Acquisition • For in vitro fertilization to work, eggs must be removed from the mother • If the mother's ovaries are not functioning (e.g. Turner Syndrome, etc), eggs must be collected from a donor • Mother's eggs are typically removed via surgery • Extra eggs can be stored

14. IVF Implantation • Fertilized eggs are incubated for several weeks before implantation • Implantation is accomplished via catheter • The same kind of catheter used for chorionic villus sampling • Leftover eggs may be harvested for embryonic stem cells or discarded

15. IVF Analogues • Gamete intrafallopian transfer (GIFT) • Sperm is placed directly into woman's oviduct during ovulation • Zygote intrafallopian transfer (ZIFT) • Fertilization accomplished via IVF then implanted directly into mother through surgery

16. Surrogacy • An arrangement can be made with another woman if the mother's uterus cannot sustain a baby • May be artificially inseminated or have the embryo implanted, for different types of surrogacy • This has the potential to introduce complications • Not legal in every state

17. Risks of ART • As with any pregnancy, individual chances of fertilization and implantation are not 100% • Even fertile couples must typically “try” for months • To minimize costs, multiple fertilizations and implantations are carried out with each procedure • Half of all IVF births are multiple births

18. Major Risks of IVF • Multiple births • Premature birth, low birth weight, etc • Ectopic pregnancy • Implantation in fallopian tube, extremely dangerous • Increased risk of chromosomal deletions using ICSI

19. Genetic Screening • Genetic screening is testing for a disease without prior indication that the disease is present • Predictive instead of diagnostic • The entirety of the US performs newborn screening for PKU (most common metabolic disorder) • Some states test only a few diseases, some test many

20. Newborn Screening • California's full list of screening targets: http://www.cdph.ca.gov/programs/nbs/Documents/NBS-DisordersDetectable011312.pdf • This is relatively uncontroversial and in general a very good preventative step

21. Preimplantation Genetic Diagnosis • When creating embryos via IVF, a single cell from the blastomere (ball of cells) can be removed and tested for genetic disorders • Called preimplantation genetic diagnosis (PGD) • Typically performed when child is at risk for a genetic disorder

22. PGD Controversy • These parents had a daughter with Falconi anemia • They had a son who they screened with PGD to ensure he would not have the same disorder • The son's cord blood was used to treat the daughter's disorder • Was he grown specifically to be a donor for the daughter? • Is that legit?

23. Cord Blood • Blood from the umbilical cord of a baby contains adult stem cells just like red bone marrow • Some hospitals save it for research and transfusion • No database for it so it's more hit-or-miss

24. Gene Therapy • Gene therapy has been studied for some time • Curing genetic diseases by inserting the missing gene into a patient's cells • Usually uses a retrovirus to write the DNA into your cells • Early experiments seemed promising but many patients died in bad reactions to the viral vector • Also some patients contracted cancer from the gene being inserted into another gene

25. Gene Therapy Categories • Currently the only type of gene therapy is somatic gene therapy • Modifying adult cells in a patient • Most successful in fighting cancer • Potential for germ-line gene therapy • Modifying the genes of gametes or embryos so all cells will have DNA • Any future children will also have same gene! • We already discussed the potential for Enhancement gene therapy

26. Genetic Counseling • Genetic counseling is a process where a geneticist will analyze the DNA of parents and advise them on the risks for genetic disorders • Accomplished using pedigrees, DNA sequencing, and medical history • Genetic counseling is important for anyone with risk to their pregnancy

27. Have a good weekend!