Assisted Reproductive Technology
Richard Paulson (Chief, Division of Reproductive Endocrinology and Infertility, USC) gives expert video advice on: How often do assisted reproductive technology treatments produce multiple children?; Are assisted reproductive technology treatments expensive? and more...
What is "assisted reproductive technology"?
The term "assisted reproductive technology" is a term that we use to class all of the different techniques together. Really, the first assisted reproductive technology was IVF, in vitro fertilization, in which eggs are removed from the woman's body, fertilized, allowed to become embryos, and then placed back into her uterus through the cervix. As time went along, this technique was modified, and we discovered different twists and turns. For example, GIFT, which stands for gamete intrafallopian transfer, involves taking the eggs and sperm, putting them together, and without waiting for fertilization to occur, putting them back into the fallopian tubes. ZIFT is another method of assisted reproductive technology, in ZIFT the eggs and sperm are combined in the laboratory and then only 24 hours later, just after the egg and sperm have come together, we put them back into the fallopian tubes. All of these assisted reprodutive techniques share the concept that the ovaries are stimulated and the eggs are collected and combined with sperm in the laboratory, then somehow the combined eggs and sperm are put back into the woman's body or perhaps someone else's body. That is why the term "assisted reproductive technologies" was invented, to put all of them together under this one heading. And of course it is abbreviated as A-R-T, or ART, so when we talk about "State of the art", it has a double meaning. But "assisted reproductive technologies" simply refers to all of these techniques mentioned together.
What are some possible side effects of assisted reproductive technology?
The side effects of assisted reproductive technology are focused primarily on the fertility medications themselves and, of course, the reality that we produce multiple eggs as a result of assisted reproductive technology. The two big side effects are multiple pregnancy, which happens in really more than a third of all pregnancies with assisted reproductive, with assisted reproductive technologies, and also ovarian hyper stimulation syndrome, which happens when the body overreacts to the fertility medications or when too much fertility medications are used. The other side effects would be complications related to egg retrieval. Whenever you poke the body with a needle, which is what we are doing, there's always a risk of bleeding or even possibly infection but these are really rare side effects. Multiple gestation and ovarian hyper stimulation, which happens in a mild form in perhaps five to ten percent of cases, and in a severe form in about one percent of cases are the most commonly associated issues with assisted reproductive technology.
What is a "gamete intra-fallopian transfer" or "GIFT"?
Gamete intra-fallopian transfer, which is abbreviated G I F T, or gift, is a modification of the basic in-vitro fertilization technology. Just as with IVF, the ovaries are stimulated and the eggs are collected and they are mixed with sperm. The difference is that with IVF we leave the egg and sperm together in the laboratory, allow fertilization to occur, and then actually let the embryo grow for a couple of days before we put the embryo back in the uterus. In contrast, with GIFT, you take the egg and the sperm, and you put them into the fallopian tube before fertilization has occurred. This has the advantage for some couples who are unhappy about the idea of egg and sperm meeting outside of the woman's body, that they do not have to have this be a part of their fertility treatment. In fact it's possible to introduce the egg and the sperm in such a way in the catheter that they literally do not touch until they are in the woman's body. So, it's a modification that in a sense takes us closer to the ideal of natural conception, in that egg and sperm are meeting in the right place and the right time, which is in the fallopian tube, right after ovulation, rather than spending any number of days in the laboratory.
What is a "zygote intra-fallopian transfer" or "ZIFT"?
Zygote intra-fallopian transfer, or ZIFT, is an assisted reproductive technology in which the egg and sperm are allowed to come together to form an early embryo -- also called a zygote. Then the embryos, or the zygotes, are placed in the Fallopian tube so that they may arrive in the uterus via the natural route, which is through the Fallopian tubes. It is used as an alternative to IVF (in vitro fertilization) in cases where perhaps IVF is not working, or in women in whom the standard form of embryo transfer is very difficult -- such as women who have had previous surgery on their uterus or women who may have an ‘anomalous uterus,' meaning a uterus that has a funny shape to it, such as it's heart-shaped or V-shaped or Y-shaped. Those women seem to do better if we do a ZIFT procedure rather than regular IVF or the standard embryo transfer.
What is an "intra-cytoplasmic sperm injection" or "ICSI"?
Intra-cytoplasmic sperm injection, abbreviated ICSI, or "ick-see" commonly, is the technique that is used to achieve fertilization in those couples in whom the male has sperm that are not capable of fertilizing the egg in a normal situation. So, in normal assisted reproductive technology, the sperm are simply added to the egg, and the assumption is that the sperm will swim around and then will fight it out and one of them will make it into the egg to achieve fertilization. But for some men, this is not the case. So their sperm are too few in number, or they're not strong enough, or they're not swimming well enough, and yet the head of the sperm contains perfectly normal chromosomes and can produce a perfectly normal offspring. So, in these conditions, the sperm is picked up, individually, one at a time, and then the sperm is actually injected directly into the egg. And because the egg consists mostly of cytoplasm, the ICSI procedure is called intra-cytoplasmic sperm injection--in other words, injection of the sperm directly into the substrate of the egg to help fertilization occur.
What is "follicle aspiration, sperm injection and assisted follicular rupture" or "FASIAR"?
Follicle aspiration sperm injection and assisted rupture are abbreviated F.A.S.I.A.R.; “FAY-zur” or “FAY-zhur” if you will, and was a technique which we used at one time to try to help egg and sperm come together without having to go through the whole rigmarole of assisted reproductive technology, and yet have some of those features be present in what would otherwise have been a simple intrauterine insemination or IUI. We tried this method for a while and it seemed to be working quite well. Others had tried it before us and given it different acronyms, but the principle was always the same. The idea was that a needle would be inserted into the follicle as though an egg was going to be taken out of it, but rather than gathering the eggs in a formal way and mixing them in the laboratory, the egg would simply be forced out of the follicle through assisted rupture of the follicle, if you will, along with the injection of the sperm, so it had lots of theoretical advantages over the simple intrauterine insemination. The trouble is that up to this point it has not been shown to be superior to a simple intrauterine insemination and so the IUI, which is less involved and less costly, continues to be used, whereas FASIAR has not really caught on and is really awaiting confirmation that it's worthwhile over the IUI.
How often do assisted reproductive technology treatments produce multiple children?
Assisted reproductive technologies, especially the way they are practiced in the United States, have a high association of multiple gestation and the reason for this, of course, is because the doctors that practice IVF, or practice assisted reproductive technologies, are as motivated as the patients to try to make the procedure be successful, so they try to tip the balance in their favour by transferring multiple embryos. If one embryo has a 20% chance of implanting, then two embryos will have will have a higher chance of implanting, and so on. It's like rolling multiple dice in an effort to get at least one of them to come up with the number six. However, if you roll four dice, every once in a while, those dice will all come up with sixes and then you'll have a multiple gestation. So, in the United States the multiple gestation rate is about 37%. It's quite high. More than one third of all pregnancies in the United States from assisted reproduction are multiple gestations. In contrast, in Europe or in other parts of the world where infertility is covered by insurance, the insurance company commonly mandates that no more than one embryo may be replaced. Well, if you only put back one embryo, then you can really only have one baby, unless of course that one embryo splits into identical twins, but that's very rare. The reason we have multiple gestations with assisted reproduction is because we're putting back multiple embryos. So, if you only put back one embryo, really, you should only have one baby, and the incidence of multiple gestation in Europe and other places in the world where infertility is covered by insurance is much lower, and really approaches what it would be in nature, which is about one percent.
Are any major lifestyle changes necessary while undergoing assisted reproductive technology treatments?
In assisted reproductive technology, we take such control over the whole reproductive process that major changes in lifestyle are not necessary. We are in control over the ovaries, how quickly the eggs grow and how they are fertilized in the laboratory. It seems quite difficult to understand how any lifestyle change could possibly impact that technique. Having said that, we generally discourage patients from drinking. We say you should consider yourself to be pregnant from the time you start. We discourage them from overly vigorous exercise. I tell them not to start training for a marathon in the middle of a fertility cycle, but light exercise, or reasonable aerobic exercise, is OK. Having sex is OK, at least until the time the embryo is put back into the uterus. There are no special foods and no special restrictions on anything else. Really everything else is pretty much OK, because we're controlling everything in such a tight way that lifestyle really plays a very minor role at that level.
Are assisted reproductive technology treatments expensive?
Assisted reproductive technology in general is very labour intensive, both for the patient as well as of course the fertility clinic. The patient has to have multiple office visits, take multiple injections, and the clinic has to do ultrasounds, exams, blood tests, and then of course after the eggs are retrieved not only the egged or tubal process itself, but then all the work in the laboratory that involves finding the eggs, fertilising them, watching the embryos, and transferring them from dish to dish. So, quite a lot of work goes into this process and as a consequence IVF is quite expensive relatively speaking. A ball park figure in the United States is about $10,000 for one cycle. Some of that of course is the cost of the medication, but most of it is the cost to the clinic and to all the people that are doing the work. For comparison a minor surgical procedure in an outpatient surgery centre; such as a tubal ligation or a laparoscopy or an arthroscopy; all those procedures cost about $10,000 it's a ball park figure in that same kind of range. Medical intervention in general is quite expensive in the United States. There are very high standards for all the material that have to be used. Every piece of equipment has to be certified for human use and so on. So, the costs are quite high all the way along the way. From the perspective of a minor surgical procedure IVF is not that expensive, but compared with just going to the doctor for an office visit, of course it's quit expensive.
Do insurance plans normally cover assisted reproductive technology treatments?
It is an unfortunate fact that in the United States the majority of insurance plans do not cover infertility treatment. That is, of course, not the case everywhere, and it really depends on what state you live in. For example, a New York, Massachusetts, an Illinois, and Arkansas have mandated coverage, and that means that everyone that works and has health insurance in those states has infertility coverage. Most states of the union, however, do not have mandated coverage and as a consequence, infertility is not covered by most insurance plans. Of course, it depends on the individual. That is not universally true. We do have patients here in California that come in with insurance. But the majority of patients, I think need to expect that this is something they are going to have to pay for out of pocket.