Reproductive Technology

Chapter 21

Assisted ReproductionWhen a couple is sub-fertile or infertile they

may need Assisted Reproduction to become pregnant:

• Replace source of gametes– Sperm, oocyte or zygote donors

• Aid in the fertilization process

• Replace the uterus– Surrogate mothers

• Treat cause of infertility

Infertility• Clinically defined as inability to conceive

after more than one year of intercourse without contraception

• World Health Organization– Defines sub-fertility as diminished ability to

conceive– Infertility as complete inability to ever

conceive

• Personally– Means changing your entire life plan

Infertility Statistics

• Affects about 1 in 6 couples in USA

• Cause can be identified in about 85% of cases

• Can be treated successfully in about 85 – 90 % of couples

• Problem in female – 50%

• Problem in male – 30%

• Problem in both partners – 20%

Male Infertility

Problems:

• Oligospermia – low sperm count– Caused by: hormones, environment, physical

• Poor sperm quality– Motility – sperm can’t swim– Abnormality – sperm are abnormally shaped

• Antibodies against own sperm– Autoimmune disorder

Genetics of Male Infertility

• Oligospermia – low sperm count– Genes: hormones, Y chromosome

abnormalities, testicular/prostrate development – Environment: drugs, toxins, heat (kills)

• Poor sperm quality– Genes: hormones, enzymes to harness energy– Environment: drugs, toxins, heat (mutates)

• Antibodies against own sperm– Genes: Immune system malfunctioning

Treatment of Male Infertility

• Primary – change environment– Avoid heat, drugs, toxins– Timing intercourse

• Secondary – correct hormone levels, surgery corrects physical problems, immune suppressants

• Final – Assisted Reproduction Technologies

Female Infertility

Problems:

• Irregular/malfunctioning ovulation– Hormone imbalance, malfunctioning or absent

ovaries or tubes

• Physical blockage– Fibroids or Endometriosis– Blocked/abnormal Fallopian tubes

• Vaginal secretions– Hormones or certain diseases

Female Infertility

Genetics of Female Infertility

• Irregular/malfunctioning ovulation– Genes: Hormones, thyroid, pituitary problems– Environment: Birth control, stress

• Physical blockage– Genes: Cancer, developmental defect – Environment: Cancer or infections

• Vaginal secretions– Genes: Hormones, mucus disorders, immune

Treatment of Female Infertility

• Primary – change environment– Timing intercourse - checking for ovulation– Decrease stress, diet, exercise, etc

• Secondary – correct hormone levels, surgery to correct physical problems

• Final – Assisted Reproduction Technologies– More often necessary for female infertility

Infertility Testing

• Couple seek testing after trying for more than one year

• Tests:– Semen Analysis (male)– Hormone levels checked (female)– Physical exams (both)– Hysterosalpingogram (HSG; female)– Endometrial Biopsy (female) – Post coital exam (done on female)

Assisted Reproductive Technologies (ART)

• Donating gametes

• Surrogate mothers

• Helping bring gametes together (fertilization)

• Putting zygote in correct place

• Preimplantation screening

Donating gametes• Sperm donation:

– For Lesbian couple or male infertility – Sperm can be inseminated into uterus or

cervix (artificial insemination)– Or sperm can be mixed with oocyte and

zygote implanted

• Oocyte donation:– Mixed with sperm and implanted as zygote– More costly and harder to come by than

semen

Surrogate Mothers• Book defines as “donating uterus”

– What else?– Also time, energy, effort, hormones, blood,

diet, health care

• Surrogate mothers:– Inseminated with father’s semen, using her

own oocytes– Or may be implanted with a zygote from

couple’s gametes

• Legal rights of surrogate mothers vary by state and country

Helping Fertilization

• IVF – in vitro fertilization– Sperm and oocyte are mixed in Petri dish– Embryo at 8 or 16 cell stage implanted into

uterus

• ICSI – intracytoplasmic sperm injection– Sperm actually microinjected into oocyte– Then embryo implanted into uterus– Important when father has low sperm count or

large number of abnormal sperm

in vitro Fertilization (IVF)

• Problem is that egg and sperm can’t meet:– Blocked tubes or abnormal structures– Not enough healthy sperm

• Put sperm and egg together in dish and then implant early embryo into uterus

• Costs $5,000 to 15,000 each try

• Success rate ~ 30%

• Children have ~ twice rate of birth defects

ICSI

• IVF where sperm is injected into oocyte

Improving IVF’s chances:

• Use ICSI

• Implanting more than one embryo– What is the problem there?

• Implant embryos at later stage in development (blastocysts)

• Culturing zygote with “helper” cells that normally surround embryo

• Screening embryos for chromosomal abnormalities

Helping Fertilization

• ZIFT – zygote intrafallopian transfer– Same as IVF only implanted into fallopian

tube rather than uterus– Less successful than IVF (~23%)

• GIFT – gamete intrafallopian transfer– Deposit the sperm directly into fallopian tubes– Or deposit sperm and oocytes (mother’s or

donor’s) into fallopian tubes– Like IVF that happens internally (~26%)

Preimplantation Screening

Screening for genetic disorders BEFORE pregnancy begins:

• One cell of 8 cell embryo is removed

• Single cell is karyotyped and probed with FISH for specific genetic disorders

• Preimplantation Genetic Diagnosis (PGD)

• Only genetically “healthy” embryo is implanted (IVF)

• ~ 29% success rate

PGD

• Screen for:– Large chromosomal abnormalities– Rare Mendelian Disorders– Boys with X-linked disorders

• PGD often done on IVF embryos to screen for chromosomal abnormalities commonly associated with IVF procedure

• Weigh risk of disease vs. IVF not working– Who could help make this decision?

“Spares”• Every time IVF is done more embryos are

made than are used

• ~ 500,000 embryos are currently in deep freeze in USA today from IVF

• Choices:– Research – example: stem cells– Donation to infertile couple– Discard them

• Who should make this choice?

Adoption• Domestic Adoptions:

– $5,000 to $40,000– Must pass stringent screening process:

Salary, housing, marital situation, criminal records

• International Adoptions:– $7,000 to $30,000– Different screening processes

• Foster Care Adoptions:– Free or subsidized – older and abused children

Lets Talk about Ethics…

• Get into groups of four

Discuss what you think of each of these ART situations as if you were:

1. One member of couple in question

2. Politician (pro life and pro ART)

3. Insurance company representative

4. Genetic counselor

Ethics of ART

1. A young, married couple is infertile. They have basically no insurance because he works as a free lance consultant and she works two part time jobs. Although they own a home and can afford to raise a child they can not afford to undergo the testing or treatments for their infertility. Neither can they afford adoption.

Ethics of ART

2. A lesbian couple has one child. The mother was inseminated from a sperm donor and carried the baby produced from her own oocyte. They happily raise the child together for 6 years, until the mother suddenly finds religion and decides that homosexuality is wrong. When they break up the mother wants the child but so does her ex.

Ethics of ART

3. An infertile couple has insurance that covers IVF but they don’t believe in using ART because of their religion. They would rather adopt, but their insurance doesn’t cover adoption (most don’t) and they can’t afford it.

Ethics of ART

4. An infertile couple uses Clomid (a drug that stimulates ovulation) to become pregnant. Suddenly they find themselves pregnant with 6 embryos. They don’t believe in selective reduction so they are going to try to carry all 6 babies to term. Their doctor knows that the babies won’t be healthy. The father concurrently loses his job, so now they have no insurance.

Ethics of ART

5. A couple wants to use PGD to make sure they have a girl.

What would you think if:

a) They have 5 boys and want a girl

b) They live in China and can only have one child

c) They know the mother carries an X linked disease

Next Class:

• Read Chapter 22

• Homework – Chapter 21 Problems;– Review: 1, 2, 9– Applied: 1, 4, 5, 6, 10, 11