The field of assisted reproduction, or reproductive technology (often called ART), dates to the birth of the first "test tube baby," Louise Brown, in England in 1978. The term assisted reproduction is used to indicate the conception of children by means of technology designed to assist the fertility efforts of couples or individuals who might not be able to conceive children without technological assistance.

In vitro fertilization

In vitro fertilization (IVF) is the process by which a woman's ovaries are artificially stimulated with fertility drugs. The drugs are injected into the woman, whose eggs, released from the ovaries, will be stimulated to develop, grow, and mature with the aid of the administered medications. This process, also known as hyperstimulation, is physically demanding and carries some risks for the woman whose eggs will be retrieved. The mature eggs are retrieved using a needle inserted intravaginally and guided by ultrasound technology, requiring only a local anesthetic. The older technique of administering general anesthesia and aspirating the woman's eggs through laparoscopy is used less often.

After retrieval, each egg is cultured in a separate laboratory dish and combined with sperm from the woman's partner or from a donor; when the sperm penetrate the egg, fertilization results and IVF has occurred. This happens in an incubator under highly controlled laboratory conditions that mimic the internal body environment. As the fertilized eggs grow and divide, early embryos develop. Technological advances have made it possible to allow the embryos to grow in culture for up to six days, at which point the blastocyst is formed. A blastocyst is often referred to as a pre-embryo because it has yet to implant itself in the uterine wall; after implantation it will become a developing embryo. Allowing pre-embryos to develop to the blastocyst stage, in vitro, enables scientists to select those embryos for implantation that are deemed to have the highest chance for a resulting pregnancy, which is the goal of the process.

In order to enhance the chances of pregnancy, it is standard procedure to transfer several embryos back into the uterus (bypassing the fallopian tubes). Consequently, although birth rates are relatively low (ten to thirty percent by most estimates), in the early years of IVF the rate of multiple births was often comparatively high. Over the last decade, in part due to the freezing of embryos (cryopreservation), scientists are able to select fewer embryos for transfer at one time, based on the health and quality of the early embryos in culture. Thus the odds of a woman having a multiple pregnancy are reduced. IVF was performed successfully for the first time in the United States at the Jones Institute for Reproductive Medicine in Norfolk, Virginia.

Blastocyst transfer

Blastocyst transfer, or embryo transfer, is the process by which the pre-embryo is transferred from the laboratory culture dish to the woman's uterus via a tiny hollow needle. Since a fertilized egg subdivides into cells over time (fertilization is a process that takes between twenty-four and forty-eight hours after the sperm penetrates egg), it has been proven to be useful to maintain the process in culture until the fertilized egg has reached cell division of between four and sixteen cells (five to six days is optimal). The transfer of the blastocyst or pre-embryo at this stage then increases the chances of survival in utero and decreases the chances of abnormal or defective embryos being implanted. Developing embryos that do not survive through the blastocyst stage have been found to have chromosomal deficiencies that are not optimal for healthy pregnancies.

Other technologies

Other reproductive technologies related to IVF include intracytoplasmic sperm injection, pre-implantation genetic diagnosis, gamete intrafallopian transfer, and zygote intrafallopian transfer. Somatic cell nuclear transfer, a developing and controversial technology, is associated with human cloning. Each of these techniques makes use of the basic process of IVF but refines the process in ways that are specific to one or more obstacles to fertility.

Intracytoplasmic sperm injection. (ICSI) is a technique developed in 1992 that is used primarily to assist in male factor infertility cases where sperm count is low or nonexistent. In this procedure, sperm are individually isolated by means of micro-manipulation and are then individually inserted into the cytoplasm of the retrieved egg in a culture dish. It is possible to combine ICSI with Microsurgical Epididymal Sperm Aspiration (MESA) and Testicular Sperm Extraction (TESE). In MESA, sperm are retrieved from the part of the testes where they mature and are stored; then ICSI is used for the fertilization process. In TESE, the testes are biopsied so that sperm can be obtained from the testicular tissue directly; then ICSI is used to fertilize the sperm.

Pre-implantation genetic diagnosis. (PGD) allows scientists to screen embryos prior to implantation to check for genetic diseases and defects. The technique combines ICSI with IVF and blastocyst transfer. The developing pre-embryos are allowed to grow in culture to the six-to-eight cell stage, at which point one or two cells are removed and biopsied to check for chromosomal abnormalities or single gene defects by analyzing the DNA. Those embryos found to contain chromosomal abnormalities or gene defects are not transferred to the uterus, and scientists are able to select "normal" embryos for transfer with the goal of a pregnancy and birth free from disease. Specifically, fertility clinics using PGD are able to test for single gene defects such as, for example, cystic fibrosis, Tay-Sachs disease, thalassemia, sickle cell anemia, x-linked diseases such as hemophilia and muscular dystrophy, and spinal muscular atrophy. PGD can also test for abnormal numbers of specific chromosomes and associated diseases such as Trisomy 21/Down syndrome, Turner's syndrome, and other such conditions.

PGD, combined with IVF, has been used successfully in several cases, some of which are ethically controversial. On August 29, 2000, Adam Nash was born as a result of this procedure. Adam's parents chose to use PGD to make sure that, in vitro, only embryos found not to contain Fanconi's anemia disease would be transferred to the uterus of Adam's mother. Adam's older sister, Molly, had Fanconi's anemia, a rare bone marrow disease, and her only hope of a cure was a bone marrow transfer from an exact donor match. After Adam was born, cells were collected from his umbilical cord and transplanted into Molly's circulatory system.

The ethical controversy surrounding the Nash case centered on two issues: (1) whether it is permissible to create a child as a means for assisting someone else (in this case, his sister); and (2) whether it is ethical to allow screening and selection of traits and conditions prenatally. The second issue raises the specter of what has colloquially been referred to as designer babies. Ethicists tend to be wary of the move to use technology prenatally to select out various traits, although the use of this technology to avoid conceiving a child with a destructive disease such as Tay-Sachs is, for many ethicists, less morally problematic than selecting out, for example, children with Down syndrome. The technique of PGD, combined with continuing advances from the Human Genome Project, raises the theoretical possibility of selecting out embryos for implantation based on traits connected with certain genes. For example, should the genes for homosexuality, intelligence, obesity, or a host of other conditions be clearly identified, it would be possible to select for or against those embryos by means of IVF and PGD.

Gamete intrafallopian transfer. (GIFT) and its related technology, zygote intrafallopian transfer (ZIFT), are technologies that use donor gametes (sperm or egg) combined with IVF to transfer the resulting embryo to the fallopian tubes of the woman who wishes to conceive. Specifically, in GIFT, fertilization occurs in vivo, in the body. ZIFT places already developed zygotes into the fallopian tubes.

When donated gametes are used for this process, donors are usually paid, raising issues about the commodification of reproduction (Holland). Such procedures make it possible for single persons and gay and lesbian couples to have children using assisted reproduction. Selection of donor gametes also raises the issue of eugenics (selective breeding) because it is now widely possible to "shop" for gametes by making up a list of desirable factors and finding them with the help of egg and sperm brokers.

Somatic cell nuclear transfer. (SCNT) is another form of assisted reproduction. This process, famously pioneered on Dolly the sheep and announced in 1997 by Ian Wilmut and his colleagues, has been experimented with in human fertility clinics. In its simplest sense, somatic cell nuclear transfer involves taking an adult somatic cell (not a reproductive cell), removing its nucleus, and transferring the DNA into an enucleated (containing no nucleus) donor egg. The donated egg is then "tricked" into the fertilization process by an electrical (or chemical) stimulation and begins cell division. Theoretically, the cloned embryo would then be implanted in the uterus using IVF techniques. Although several kinds of animals have been cloned, primates have not, and as of mid-2002, there is no public evidence that human cloning has been attempted, though there have been reports that Antinori Severino, an Italian fertility doctor, is engaged in this work.

The American public has been overwhelmingly opposed to the use of SCNT because it raises fears of madmen such as Adolf Hitler cloning armies of an Aryan master race, and other such scenarios. The technology is so difficult that these fears have no grounding in fact; however, it will certainly be possible one day to "clone" a human being via the process described. This type of cloning may be accurately thought of as "delayed twinning," for the cloned child would in fact be the genetic twin of the original donor. It raises some of the same ethical concerns as those raised under PGD, although at this point PGD technology has proven to be safe, while SCNT is not at all safe for use in human reproduction. As such, several ethics advisory boards, including the National Bioethics Advisory Commission (1997) and the California Advisory Committee on Human Cloning (2002), have recommended a moratorium on the use of this technology in humans until such time as it is proven to be safe.

Fertility specialists are also working on nuclear transfer techniques that would make it possible for a woman who wishes to conceive to have the nucleus from one of her unfertilized eggs removed and inserted into an enucleated egg donated by another woman. This is nuclear transfer, but not with a somatic cell. The goal of this procedure, when perfected, will be to assist older woman whose eggs are not ideal become pregnant using the eggs from a younger woman while retaining the DNA from the mother-to-be. One pioneer of this technique is Jamie Grifo at New York University Medical Center (Holt).

Religious responses

Assisted reproduction is now widely used around the world, and especially in the United States, although specific techniques continue to be of concern to ethicists, and religious communities have a variety of perspectives on the matter. The religious institution most clearly opposed to assisted reproduction is the Roman Catholic Church. In its 1987 instruction Donum Vitae (Gift of Life), the Catholic Church clearly states: "Through in vitro fertilization and embryo transfer and heterologous artificial insemination, human conception is achieved through the fusion of gametes of at least one donor other than the spouses who are united in marriage. Heterologous artificial fertilization is contrary to the unity of marriage, to the dignity of the spouses, to the vocation proper to parents, and to the child's right to be conceived and brought into the world in marriage and from marriage" (O'Rourke and Boyle, p. 63). Thus the Roman Catholic Church's objection to assisted reproduction is grounded in classical natural law theology that opposes the separation of procreation from the conjugal act of love in marriage. Nevertheless, many Catholics in the United States deviate in practice from their church's official teachings on contraception, abortion, and assisted reproduction.

Moderate and liberal Protestant denominations in the United States, often referred to as mainline Protestant, include the American Baptist Church, the Episcopal Church, the Presbyterian Church USA, the United Church of Christ, the United Methodist Church, and the Evangelical Lutheran Church. In general, these denominations emphasize fidelity to Scripture in formulating one's moral response to a situation, as distinct from the emphasis on church doctrine or tradition that one finds in Roman Catholicism. Thus, as Christian Green and Paul Numrich point out in their 2002 book, Religious Perspectives on Sexuality, these mainline Protestant denominations, while they have a variety of official responses to reproductive issues, tend to affirm the right of individuals to discern for themselves how to make use of reproductive technologies.

Conservative Protestantism includes the Southern Baptist Convention, the Assemblies of God, the Association of Vineyard Churches, and a variety of independent, evangelical fundamentalist churches. They have in common with mainline Protestants an emphasis on the primary authority of the Bible, but these churches are generally distinguished by an insistence on a literal interpretive framework. Their positions on reproductive matters tend to include an active opposition to abortion, but assisted reproduction has not been much considered in formal church statements. In general, "They tend to approve of methods intended to correct physical problems that cause couples to be infertile, but they disapprove of methods that would violate the sanctity of the marriage bond by using donated sperm and eggs, as well as any method that would tamper with or discard a fertilized embryo" (Green and Numrich, p. 11).

The three branches of Judaism—Orthodox, Conservative, Reform—each have a variety of responses to assisted reproduction and their concerns are relative to the importance each branch places on upholding Jewish law or halachah. Assisted reproduction tends to be permitted in most branches of Judaism, although there are more and less problematic forms of reproductive technologies. Those forms of assisted reproduction that make use of the eggs and sperm of the couple trying to conceive are less problematic than those that make use of donor gametes; indeed, in Orthodox Judaism, donor gametes raise concerns of adultery. Surrogacy, too, is permissible for Jews, and there is ancient Biblical precedent for it. Since conception and the raising of children are cornerstones of Judaism, assisted reproduction tends to be viewed as permissible and even a good thing if it results in childbearing. Moreover, since, for example, Tay-Sachs disease is a devastating disease for Ashkenazi Jews, the use of PGD and other forms of assisted reproduction that prevent the birth of Tay-Sachs children has been widely embraced by Judaism. Moreover, therapeutic cloning (using SCNT for obtaining stem cells) has been approved by the Union of Orthodox Jewish Congregations of America and the Rabbinical Council of America, the two largest Orthodox Jewish organizations. It is widely expected that the other branches of Judaism will follow suit (Cooperman, Dorff).

Islam is also characterized by many schools of thought and practice: Sunni Muslims consider themselves followers of Muhammad's tradition; Shiite Muslims, the second-largest branch of Islam, adhere to the authority of the supporters of Ali, Muhammad's son-in-law; Sufi Muslims, the smallest branch, stress mysticism and personal worship. In the United States, many African-Americans have joined the Nation of Islam, which is based on the teaching of Elijah Muhammad. So although there is a wide variety of Islamic expression and values, in general the views of Islam on assisted reproduction are similar to those of Judaism in that most forms of assisted reproduction are permitted, with the caveat that only the eggs and sperm of the married couple are used. Surrogacy, however, is generally not permitted.

See also CHRISTIANITY; CHRISTIANITY, ROMAN CATHOLIC, ISSUES IN SCIENCE AND RELIGION; CLONING; ISLAM; JUDAISM; REPRODUCTIVE TECHNOLOGY

SUZANNE HOLLAND