Deck 16: Reproductive Technology, Genetic Testing, and Gene Therapy

Question 1

List the common infertility problems in women. What is the major infertility problem in men? Is it correctable?

Answer 1

Being infertile describes an individual who is sterile, or cannot reproduce. Infertility results from unhealthy gametes, a malfunction of the uterus, and a malfunction of the oviduct. The oviduct is the area in a woman where fertilization occurs. The uterus is a component of a woman's reproductive system where the embryo grows and develops.
Common infertility problems in women:
•Hormone-related ovulation problems - low levels or no presence of estrogen does not allow ovulation to occur.
•Cervical problems
•Oviduct blockage - can be caused by a sexually transmitted disease, or viral infection
•Uterine problems - may be caused by endometriosis, a problem with the inner lining of the uterus.
•Damaged or absent ovaries
•Weight - being underweight or overweight
•Age
Common infertility problems in men:
•Semen disorders
•Testicular failure
•Obstruction
•Undescended testes
Several of these problems but not all can be correctable. In a woman's case, hormone-related problems can be fixed with hormone supplements. When a woman experiences a hormone imbalance, it is most likely due to her being overweight. Losing weight can act as a correction to hormone imbalance.
In the male's case, insemination can be used to assist the infertility problem occurring. Insemination is a system used to insert donor sperm into the female partner of the man experiencing infertility.

Question 2

Some fertility clinics limit donated-egg recipients to women who are 55 years of age or younger. Do you think this is an intrusion on reproductive rights?

Answer 2

This does not appear as an intrusion on reproductive rights. Those between the age of 30 and 55 are lucky to be able to receive a donated egg. Once a woman reaches the age of 35 her risk of having a child with birth defects increases. A woman's risk increases depending on a woman's health. A woman at the age of 40 can give birth to a healthy child if she is healthy. A woman over the age of 55 will experience many complications during pregnancy. She may experience a stroke, a heart attack, develop high blood pressure or diabetes.

Question 3

How does IVF differ from artificial fertilization?

Answer 3

IVF stands for In vitro fertilization. In vitro fertilization is the combination of sperm and an egg outside of the uterus. If fertilization occurs, the embryo is grown in an incubator before it is placed in the uterus to develop.
Artificial fertilization doesn't differ much from IVF. Artificial fertilization is another method to help infertile or subfertile individuals and couples have children. Artificial fertilization uses IVF for several processes. IVF may be used in artificial fertilization if the mother is infertile but able to carry a child, or both parents are infertile but the mother is able to carry a child.

Question 4

What is the difference between gamete intrafallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)?

Question 5

Why should women consider collecting and freezing oocytes for use later in life when they want to have children? What are the risks associated with older women having children?

Question 6

What do you think are the legal and ethical issues surrounding the use of IVF? How can these issues be resolved? What should be done with the extra gametes that are removed from the woman's body but never implanted in her uterus?

Question 7

Researchers are learning how to transfer spermmaking cells from fertile male mice into infertile male mice in the hopes of learning more about reproductive abnormalities. These donor spermatogonia cells have developed into mature spermatozoa in 70% of cases, and some recipients have gone on to father pups (as baby mice are called). This new advance opens the way for a host of experimental genetic manipulations. It also offers enormous potential for correcting human genetic disease. One potentially useful human application of this procedure is treating infertile males who wish to be fathers.
a. Do you foresee any ethical or legal problems with the implementation of this technique? If so, elaborate on the concerns.
b. Could this procedure have the potential for misuse? If so, explain how.

Question 8

What is the difference between genetic testing and genetic screening?

Question 9

Cystic fibrosis is an autosomal disease that mainly affects the white population, and 1 in 20 whites are heterozygotes. Genetic testing can diagnose heterozygotes. Should a genetic screening program for cystic fibrosis be instituted? Should the federal government fund it? Should the program be voluntary or mandatory, and why?

Question 10

You are a governmental science policy adviser, and you learn about a new technique being developed that promises to predict IQ accurately based on a particular combination of genetic markers. You also learn that this technique could potentially be applied to preimplantation genetic diagnosis (PGD), so parents would be able to select an embryo for implantation that is free of a genetic disorder and one that is likely to be relatively smart. What policy recommendations would you make concerning this technology? Do you think parents should have the right to choose any characteristic of their children, or should PGD be limited to ensuring that embryos are free of genetic disorders? Should guidelines be imposed to regulate this process, or should it be banned?

Question 11

Gene therapy involves:
a. the introduction of recombinant proteins into individuals
b. cloning human genes into plants
c. the introduction of a normal gene into an individual carrying a mutant copy
d. DNA fingerprinting
e. none of these

Question 12

In selecting target cells to receive a transferred gene in gene therapy, what factors do you think would have to be taken into account?

Question 13

The prospect of using gene therapy to alleviate genetic conditions is still a vision of the future. Gene therapy for adenosine deaminase deficiency has proved to be quite promising, but many obstacles remain to be overcome. Currently, the correction of human genetic defects is done using retroviruses as vectors. For this purpose, viral genes are removed from the retroviral genome, creating a vector capable of transferring human structural genes into sites on human chromosomes within target-tissue cells. Do you see any potential problems with inserting pieces of a retroviral genome into humans? If so, are there ways to combat or prevent these problems?

Question 14

Is gene transfer a form of eugenics? Is it advantageous to use gene transfer to eliminate some genetic disorders? Can this and other technology be used to influence the evolution of our species? Should there be guidelines for the use of genetic technology to control its application to human evolution? Who should create and enforce these guidelines?

Question 15

A couple who wishes to have children visits you, a genetic counselor. There is a history of a deleterious recessive trait in males in the woman's family but not in the man's family. The couple is convinced that because his family shows no history of this genetic disease, they are not at risk of having affected children. What steps would you take to assess this situation and educate the couple?

Question 16

A couple has had a child born with neurofibromatosis. They come to your genetic counseling office for help. After taking an extensive family history, you determine that there is no history of this disease on either side of the family. The couple wants to have another child and wants to be advised about the risks of that child having neurofibromatosis. What advice do you give them?

Question 17

You are a genetic counselor, and your patient has asked to be tested to determine if she carries a gene that predisposes her to early-onset cancer. If your patient has this gene, there is a 50/50 chance that all of her siblings inherited the gene as well; there is also a 50/50 chance that it will be passed on to their offspring. Your patient is concerned about confidentiality and does not want anyone in her family to know she is being tested, including her identical twin sister. Your patient is tested and found to carry a mutant allele that gives her an 85% lifetime risk of developing breast cancer and a 60% lifetime risk of developing ovarian cancer. At the result-disclosure session, she once again reiterates that she does not want anyone in her family to know her test results.
a. Knowing that a familial mutation is occurring in this family, what would be your next course of action in this case?
b. Is it your duty to contact members of this family despite the request of your patient? Where do your obligations lie: with your patient or with the patient's family? Would it be inappropriate to try to persuade the patient to share her results with her family members?

Question 18

A young woman (the proband) and her partner are referred for prenatal genetic counseling because the woman has a family history of sickle cell anemia. The proband has the sickle cell trait ( Ss ), and her partner is not a carrier and does not have sickle cell anemia ( SS ). Prenatal testing indicates that the fetus is affected with sickle cell anemia ( ss ). The results of this and other tests indicate that the only way the fetus could have sickle cell disease is if the woman's partner is not the father of the fetus. The couple is at the appointment seeking their test results.
a. How would you handle this scenario? Should you have contacted the proband beforehand to explain the results and the implications of the results?
b. Is it appropriate to keep this information from the partner because he believes he is the father of the baby? What other problems do you see with this case?

Question 19

Jan, a 32-year-old woman, and her husband, Darryl, have been married for 7 years. They have attempted to have a baby on several occasions. Five years ago, they had a first-trimester miscarriage, followed by an ectopic pregnancy later the same year. Jan continued to see her OB/GYN physician for infertility problems but was very dissatisfied with the response. After four miscarriages, she went to see a fertility specialist, who diagnosed her with severe endometriosis and polycystic ovarian disease (detected by hormone studies). The infertility physician explained that these two conditions were hampering her ability to become pregnant and thus making her infertile. She referred Jan to a genetic counselor.
At the appointment, the counselor explained to Jan that one form of endometriosis (MIM 131200) can be a genetic disorder, and that polycystic ovarian disease can also be a genetic disorder (MIM 184700) and is one of the most common reproductive disorders among women. The counselor recommended that a detailed family history of both Jan and Darryl would help establish whether Jan's problems have a genetic component and whether any of her potential daughters would be at risk for one or both of these disorders. In the meantime, Jan is taking hormones, and she and Darryl are considering alternative modes of reproduction.
Using the information in Figure 1, explain the reproductive options that are open to Jan and Darryl.
Would ISCI be an option? Why or why not?
FIGURE 1 The many ways gametes can be combined in assisted reproduction.

Question 20

Jan, a 32-year-old woman, and her husband, Darryl, have been married for 7 years. They have attempted to have a baby on several occasions. Five years ago, they had a first-trimester miscarriage, followed by an ectopic pregnancy later the same year. Jan continued to see her OB/GYN physician for infertility problems but was very dissatisfied with the response. After four miscarriages, she went to see a fertility specialist, who diagnosed her with severe endometriosis and polycystic ovarian disease (detected by hormone studies). The infertility physician explained that these two conditions were hampering her ability to become pregnant and thus making her infertile. She referred Jan to a genetic counselor.
At the appointment, the counselor explained to Jan that one form of endometriosis (MIM 131200) can be a genetic disorder, and that polycystic ovarian disease can also be a genetic disorder (MIM 184700) and is one of the most common reproductive disorders among women. The counselor recommended that a detailed family history of both Jan and Darryl would help establish whether Jan's problems have a genetic component and whether any of her potential daughters would be at risk for one or both of these disorders. In the meantime, Jan is taking hormones, and she and Darryl are considering alternative modes of reproduction.
Using the information in Figure 2, explain the reproductive options that are open to Jan and Darryl.
Jan is concerned about using ART. She wants to be the genetic mother and have Darryl be the genetic father of any children they have. What methods of ART would you recommend to this couple?
FIGURE 2 The many ways gametes can be combined in assisted reproduction.

Question 21

Trudy is a 33-year-old woman who went with her husband, Jeremy, for genetic counseling. Trudy has had three miscarriages. The couple has a 2-year-old daughter who is in good health and is developing normally. Chromosomal analysis was done on tissues recovered from the last miscarriage, which were found to be 46,XY. The last miscarriage occurred in January 2005. Peripheral blood samples for both parents were taken at the time and sent to the laboratory. Trudy's chromosomes were 46,XX, and Jeremy's were 46,XY,t(6;18)(q21;q23). Jeremy appears to have a balanced translocation between chromosome numbers 6 and 18. There is no family history of stillbirths, neonatal death, infertility, mental retardation, or birth defects. Jeremy's parents both died in their 70s from heart disease, and he is unaware of any pregnancy losses experienced by his parents or siblings.
The recurrence risks associated with a balanced translocation between chromosomes 6 and 18 were discussed in detail. The counselor used illustrations to demonstrate the approximately 50% risk of unbalanced gametes; the other 50% of the gametes result in either normal or balanced karyotypes. The family was informed that the relative empirical risk for chromosomally unbalanced conceptions is significantly less than 50%. Prenatal diagnostic procedures were described, including amniocentesis and chorionic villus sampling. The benefits, risks, and limitations of each were described. The couple expressed a desire to have another child and was interested in proceeding with an amniocentesis.
Draw each of the possible combinations of chromosomes 6 and i8 that could be present in Jeremy's gametes, showing how there is an approximately 5o% chance that they are normal or balanced and a 5o% chance that they are unbalanced.

Question 22

Trudy is a 33-year-old woman who went with her husband, Jeremy, for genetic counseling. Trudy has had three miscarriages. The couple has a 2-year-old daughter who is in good health and is developing normally. Chromosomal analysis was done on tissues recovered from the last miscarriage, which were found to be 46,XY. The last miscarriage occurred in January 2005. Peripheral blood samples for both parents were taken at the time and sent to the laboratory. Trudy's chromosomes were 46,XX, and Jeremy's were 46,XY,t(6;18)(q21;q23). Jeremy appears to have a balanced translocation between chromosome numbers 6 and 18. There is no family history of stillbirths, neonatal death, infertility, mental retardation, or birth defects. Jeremy's parents both died in their 70s from heart disease, and he is unaware of any pregnancy losses experienced by his parents or siblings.
The recurrence risks associated with a balanced translocation between chromosomes 6 and 18 were discussed in detail. The counselor used illustrations to demonstrate the approximately 50% risk of unbalanced gametes; the other 50% of the gametes result in either normal or balanced karyotypes. The family was informed that the relative empirical risk for chromosomally unbalanced conceptions is significantly less than 50%. Prenatal diagnostic procedures were described, including amniocentesis and chorionic villus sampling. The benefits, risks, and limitations of each were described. The couple expressed a desire to have another child and was interested in proceeding with an amniocentesis.
Trudy became pregnant again, and an amniocentesis showed that the fetus received the balanced translocation from her father. Is she likely to have any health problems because of this translocation? Will it affect her in any way?