Reproductive Technologies 101
Dennis M. Sullivan, MD, MA (Ethics)
Infertility is often not considered a â€œdiseaseâ€ in our society, yet it causes great pain in couples who desire to begin a family. Couples are infertile when they have actively tried to conceive without success for a year, a condition that affects 10-15% of the U.S. population.1,2 Treatments designed to help couples conceive are referred to as Assisted Reproductive Technologies, or ART.
Couples may be candidates for ART after undergoing a thorough medical evaluation. In about one-third of cases, the problem resides within the woman, and may be related to failure to ovulate, or to failure of ova to enter the Fallopian tube (one of a pair of tubes connecting the ovary to the uterus). Another third of cases are due to male factors, such as azoospermia (an absence of sperm production) or oligospermia (inadequate numbers of sperm). In the remainder of cases, the cause is a combination of factors or is unknown.2
The simplest form of ART is hormonal stimulation of the ovaries. This is accomplished by the use of â€œfertility drugsâ€ that hyperstimulate the ovaries. If a woman has failed to ovulate, such drugs may help. The down side of such treatments is that they may induce the ovaries to release more that one ovum3 per cycle, increasing the possibility of a multiple pregnancy (e.g., twins or triplets).
If the male partner is incapable of sexual intercourse, or if he has azoospermia or oligospermia, the couple may be candidates for artificial insemination. Sperm are obtained from the womanâ€™s partner, or may be provided by an anonymous donor. Artificial insemination by donor (AID) is a popular technique, though it introduces the gametes of an outside party into the relationship, which raises ethical questions (not addressed here).
A more complex intervention is intracytoplasmic sperm injection (ICSI). This may be done in the case of a decreased sperm count or decreased sperm motility. In ICSI, one sperm is injected directly into a harvested ovum (obtained by techniques described shortly), producing a zygote (fertilized ovum). The zygote is then allowed do develop into an embryo in culture, and implanted into the womanâ€™s uterus on the third day. This technique is rare, making up less than 1% of all ART interventions.
Of historical interest are GIFT (gamete intrafallopian transfer) and ZIFT (zygote intrafallopian transfer), where either gametes (ova and sperm) or a zygote are placed directly into the Fallopian tube. These are rarely done today because of advances in IVF.
In vitro fertilization (IVF) is a very popular form of ART, where fertilization of ova takes place outside of the uterus in a Petri dish (a shallow laboratory container made of Pyrex â€“ in vitro means literally â€œin glassâ€ from the Latin). Powerful endocrine hormones are used to hyperstimulate a womanâ€™s ovaries. Developing follicles are followed by ultrasound over a period of weeks. When the developing ova are ready, they are harvested by means of a needle inserted trans-vaginally, under direct ultrasound guidance.
Harvested ova are placed into a Petri dish, and where ejaculated sperm are placed as well, causing fertilization. The resulting zygotes / embryos are allowed to develop in culture. Sometimes these are implanted at the three-day old (morula) stage, which is technically easier but results in a lower success rate. The success rate can be improved by waiting until the five-day (blastocyst) stage, though this is technically more demanding. By the way, in the â€œnaturalâ€ scheme of things, it takes about 6 days for an embryo to travel down the Fallopian tube until it implants in the uterine wall.
The overall success rate for IVF is usually less than 50% per attempt. In order to improve the possibilities, some fertility centers implant six or more embryos, allowing them to develop in the womb for a few more weeks. After multiple embryos have implanted and developed, a specialist then goes into the uterus with a needle (under ultrasound guidance), and destroys smaller or less robust embryos, leaving about three. The practice is called selective reduction, and raises sanctity of life ethical concerns.
The cost of IVF for one hyperovulatory cycle may be $10,000 to $12,000, and this is not always covered by medical insurance. If previously frozen embryos are used, the cost per attempt may be only $2,000 to $3,000. Since a large number of ova (8 to 12) may be harvested at one time, cost and sanctity of life considerations make freezing embryos an attractive option, rather than simply discarding those that are not implanted. This involves special techniques of cryopreservation, and may preserve embryos for many years. However, cryopreservation of embryos raises legal questions about their status, and decreases the successful implantation percentage for each embryo.
It is not known how many â€œleftover embryosâ€ are sitting in cryogenic storage in fertility centers. Some estimates are as high as 400, 000 in the U.S. alone.4 Though it is unclear how many of these embryos will be discarded in the next few years, their presence has fueled the debate over human embryonic stem cell research.
1. McConchie D. “An Overview to Reproductive Technologies” www.cbhd.org/resources/reproductive/overview.htm. The Center for Bioethics & Human Dignity, Bannockburn, IL, 1999.
2. American Society for Reproductive Medicine www.asrm.org/whatsnew.html.
3. Note that the term ovum (pl. ova) is used here for simplicity. The actual biological entity is a secondary oocyte.
4. “Fact Sheet: The Legend of the 400, 000 Embryos” www.stemcellresearch.org/facts/2004-06-11.htm. Do No Harm Coalition, Washington, D.C.