Research > Updates > Childbirth

Did you read the articles about the parents with sickle cell trait who had babies who did not have sickle cell trait or sickle cell anemia? This is the result of a method of in vitro fertilization and preimplantation genetic diagnosis, used by investigators that guaranteed their babies would not have Sickle Cell Anemia. This issue of VIEWPOINTS answers some questions you may have about this accomplishment.

Who were the Investigators?

The investigators were Kangpu Xu, Ph.D.; Zhong Ming Shi, M.D.; Lucinda L. Veeck, MLT. Dsc; and Zev Rosenwaks, M.D., all of the Center for Reproductive Medicine and Fertility, Weill Medical College, Cornell University, New York, NY, and Mark R. Hughes, M.D., Department of Reproductive Genetics, Wayne State University, Detroit, MI. A report on their study was published in the May 12, 1999 edition of JAMA (Journal of the American Medical Association).

What is "In Vitro Fertilization" and "Preimplantation Genetic Diagnosis"?

In Vitro Fertilization is an outpatient procedure that consists of implanting fertilized eggs, after they have been fertilized with the father’s sperm in a sterile container, into the mother’s womb. It has been used for over 20 years to help infertile couples have babies. In this procedure, after the father’s sperm count has been checked, the mother is given fertility drugs for two weeks. Her eggs are then taken from her ovaries, placed in a sterile container and injected with the father’s sperm.

Investigators in this study used in vitro fertilization, and then tested the developing embryos to determine their sickle cell status. Within 24 hours, the resulting fertilized eggs can be tested for various genes before they are implanted in the mother's womb. The test is called Preimplantation Genetic Diagnosis. It has been used to detect other genetic and gender-linked inherited diseases such as Hemophilia, Tay-Sachs, Cystic Fibrosis, and Down’s Syndrome.

What did the Research Doctors find?

In Vitro Fertilization resulted in seven embryos (fertilized cells). Preimplantation Genetic Diagnosis showed that four of the seven embryos did not have a sickle cell gene; two were sickle cell trait; the status of the seventh one was unknown. Three embryos (2 that did not have the sickle gene and 1 with sickle trait) were transferred to the mother’s womb, and she became pregnant with twins. Sixteen and a half weeks after the implantation, their non-sickle cell status was confirmed by amniocentesis. Twin girls, without sickle cell trait or sickle cell anemia, were born in 1998.

Are problems associated with either of these procedures?

Counseling should be offered to couples considering either of these procedures to help them understand their options. With In Vitro Fertilization, there is the possibility of multiple pregnancies, because more than one embryo is implanted. Some experts advise the parents of multiple fetuses to consider removing some of the fetuses early in the pregnancy, but this is a very difficult choice for the parents to make. The parents in this study did not have to consider such decisions. Preimplantation Genetic Diagnosis is relatively new, and success is difficult. A very small tube that is about 1/1000^th the size of a human hair is used to remove one or two cells from the fragile embryo without destroying it. And, as with any pregnancy, where embryos are fertilized outside the womb and later implanted, there is only a 20 to 40 percent chance of a live birth.

Is Preimplantation Genetic Diagnosis ready for general use?

This is the first reported case in which Preimplantation Genetic Diagnosis was used to screen for sickle cell disease. Worldwide, fewer than 200 babies have been born after this intricate test to screen out a handful of genetic diseases. Furthermore, In Vitro Fertilization itself, costs at least $8,500 for each attempt; to which must be added the costs of Preimplantation Genetic Diagnosis. The expense involved will therefore limit the use of these techniques.

What should Sickle Cell Trait couples do now?

Couples with sickle cell trait who want to start a family should be offered counseling so they can make their own informed decisions about whether or not they wish to take a 25% chance in each pregnancy of having a child with sickle cell anemia. For some couples, the desire to have a child by traditional conception, supercedes the risk of having a child with sickle cell anemia. If they decide to take the risk, prenatal diagnosis has been available for quite a few years.

How is Prenatal Diagnosis done?

Two tests can be offered at different stages of the pregnancy, to determine the sickle status of the developing baby. In chorionic villus testing, a sample is taken from the placenta (the organ which feeds the baby) and analyzed. This test is done at about the 9^th week of pregnancy. Amniocentesis is a test performed at about 15 weeks of pregnancy in which a sample of the amniotic fluid (the bag of water) is analyzed. These techniques allow a family the option of terminating or continuing the pregnancy, as well as providing them with advance knowledge so they can be prepared for the birth of a child who may have sickle cell disease.

Why did this report get so much publicity?

The media has a responsibility to keep the public informed about new developments in all fields. So when researchers have found an apparently promising new approach to a major health problem such as sickle cell disease, it is given a great deal of attention. The success of research efforts such as this, could eventually lead to broader options for couples who may otherwise be intimidated by their sickle cell status regarding having children. As more such efforts are undertaken and widely reported, more researchers will develop projects to speed up the search for a universal cure.

What is available for persons with Sickle Cell disease?

All patients with sickle cell disease should be enrolled in an ongoing medical care program with physicians knowledgeable about sickle cell disease. Children younger than five should be placed on daily doses of penicillin to prevent the severe bacterial infections that were the leading cause of death for very young children with sickle cell anemia before penicillin was proven to be effective in preventing infections. Since there are other life-threatening complications, close follow-up is essential throughout life so that treatment can be instituted early enough to prevent disasters.

The drug hydroxyurea, recently approved for use in adults with sickle cell disease, reduces the number of pain episodes and certain lung complications in some patients. In a few reports and ongoing studies, bone marrow transplantation shows promise for a cure in selected cases.

How will I know more about this and other new developments?

SCDAA will keep you informed on this subject and other developments concerning sickle cell disease treatment and research.

Parents with sickle cell trait who would like to learn more on in vitro fertilization and preimplantation genetic diagnosis may consult local experts in Obstetrics and Gynecology: Reproductive Medicine and Fertility. You may also call SCDAA National Office (310.216.6363) or the Division of Reproductive Genetics at Wayne State University/Hutzel Hospital, 313.755.7066 for assistance in identifying a source for this information if you have difficulty locating an expert near you.

Page Updated: August, 1999