In Vitro Fertilization

In Vitro Fertilization (IVF), an assisted reproductive technology (ART) in which one or more eggs are fertilized outside a female's body. This technique has been used extensively in animal embryological research for decades, but only since 1978 has it been successfully applied to human reproduction. In human reproduction, the process involves stimulation of the growth of multiple eggs by the daily injection of hormone medications—controlled ovarian hyper-stimulation using gonadotropins (natural or synthetic hormones) or the drug clomiphene citrate (Clomid). (It is also possible to conduct IVF without the use of the hormone medications; a single egg would develop and be retrieved.) The eggs are recovered by one of two methods: sonographic egg recovery, the more common of the two, which uses ultrasound guidance under local anaesthetic to retrieve the eggs, or oocytes; or laparoscopic egg recovery, in which retrieval is made through a small incision in the abdomen and requires a general anaesthetic.

Once the eggs are retrieved, they are placed in a special fluid medium, then semen that has been washed and incubated is placed with the eggs and left for approximately 18 hours. The eggs are removed, passed into a special growth medium, and then examined about 40 hours later. If the eggs have been fertilized and developed normally, the embryos are transferred to the woman's (or a surrogate's) uterus. Typically, multiple embryos are transferred to increase the likelihood of pregnancy. If more than four eggs develop into embryos, the donor may have the option of cryopreserving the remaining embryos for thawing and replacement in a later IVF cycle. (Cryopreservation is used to minimize the risk of multiple gestations, such as twins and triplets, if more than four embryos are replaced.) Following egg transfer, progesterone injections may be administered daily to the recipient. The probability of viable pregnancy is approximately 20 per cent with one IVF cycle.

Variations on this basic technique manipulate the place of return and time after harvesting of eggs. In gamete intrafallopian transfer (GIFT), the harvested eggs and sperm are placed directly into the Fallopian tubes, with fertilization occurring in the woman's body. In zygote intrafallopian transfer (ZIFT), the procedure is similar to GIFT, but the beginning-stage embryos (zygotes) are placed directly in the Fallopian tubes. Tubal embryo transfer (TET) returns older, four- to eight-cell embryos at 24 hours after fertilization to the Fallopian tubes. With superovulation uterine capacitation enhancement (SOURCE), the woman receives daily hormone medications to stimulate the growth of multiple eggs. Once the eggs have reached the right stage, intrauterine inseminations (IUI) are done using the partner's specially treated sperm. Post-fertilization techniques of assisted hatching use microsurgical needles or chemicals to make a microscopic hole in the zona pelucida (“clear zone” around the egg) to enable the embryo to be released from the egg’s membrane. Donor oocyte programmes are available in some places; women unable to use their own eggs to achieve pregnancy use donated eggs. Assisted reproductive technology is used to retrieve eggs from donors and replace embryos in the recipient.

While these techniques have used IVF to counter female infertility, ways to collect and manipulate sperm have developed. Intracytoplasmic Sperm Injection (ICSI) uses a needle to insert a single sperm directly into a harvested egg, overcoming problems of low sperm count. Microinsemination concentrates sperm, in small drops of fluid, before this is put around the egg to try to increase the fertilization rate. These procedures currently have lower rates of success than classic IVF, but do offer the potential of parenthood to a wider range of infertile people.

The advent of IVF and the human embryology it made possible (including stem cell research after 1998) raised new ethical issues. In the United Kingdom, the Warnock Committee (convened in 1982) published its report in July 1984 and called for legislation to regulate and license these procedures and research. A Voluntary Licensing Authority (1985), established jointly by the Medical Research Council and the Royal College of Obstetricians and Gynaecologists, took on an advisory role before the Human Fertilization and Embryology Authority (HFEA) was mandated with these responsibilities from August 1, 1991, following the Human Fertilization and Embryology Act of April 1990.

In January 2000 the ban on women in the United Kingdom using their frozen eggs in fertility treatment was lifted. The decision by the HFEA means that women are now able to delay starting a family. The ruling is of particular help to those women who have been rendered infertile by cancer treatment. It had been feared that the freezing and thawing process could damage a baby's genes, giving rise to birth defects. However, in the light of developments in the United States and Japan, where 25 healthy babies had been born in the previous three years from pregnancies that developed from frozen eggs, the HFEA concluded that the procedure is safe, although not free from risk. In a further development in April 2003, it was confirmed in a court ruling that the HFEA had the power to license the tissue-typing technique that uses IVF technology to screen embryos genetically before selection—preimplantation genetic diagnosis (PGD).

In PGD, at the four- to ten-cell stage of the zygote, a cell is removable without interrupting normal development. The cell’s genetic material can then be tested for specific abnormalities (for example, cystic fibrosis), although only one disorder may be tested for at a time. It is also possible to conduct aneuploidy screening and determine if the number of chromosomes is normal or abnormal (for example, for Down’s syndrome). A healthy embryo can then be implanted. The sex of the embryo can also be determined and sex-linked recessive conditions avoided. Sex selection merely for choice is prohibited by the HFEA. PGD can obviate the need for prenatal testing and subsequent abortion and uses IVF to help normally fertile couples produce healthy children, where there is a risk of a genetic disorder in the family history. The production of so-called “designer babies” using PGD-selected embryos facilitates the potential for later tissue transplants between the younger donor or “saviour sibling” and an older sick child who expresses a genetic disease, for example, Diamond Blackfan Anaemia, an incurable blood disorder.