Reproductive Technology

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

Fertility

Not all people are naturally able to produce children

Infertility is approximately equally common in men and women Increases with age

in women

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

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

Female Infertility

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

Male Infertility

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

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

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

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

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

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

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

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

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

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

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

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

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

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?

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

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

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

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

Have a good weekend!