IVF: what it can and can’t doNovember 12, 2010Carole 4 Comments »
I love embryology and IVF and realize it has opened new possibilities for people to have and raise children that didn’t exist 35 years ago. But I also know IVF is not the answer for every person with infertility problems. Sometimes we fall in love with a technology and expect too much from it. In this post, I want to talk about what IVF can do and what it can’t do so that you can decide for yourself when to use this technology and when it won’t benefit you.
First of all, IVF is not one procedure but a range of procedures with different parts that can help the male or the female side of things.
Ovarian Stimulation. Obviously, this is for the female. The ovarian stimulation phase of IVF controls the menstrual cycle with medications that push the ovary to produce more eggs (gonadotropins) and ovulate (hCG trigger shot to mimic natural luteinizing hormone). Having more eggs to work with (compared to 1-2 in a natural cycle) for an IVF cycle is necessary to optimize the chances of IVF working. Some women never ovulate or ovulate irregularly. Ovarian stimulation medications can be used to over ride this problem and restore fertility. Aah, you say, but you don’t need in vitro fertilization to get this benefit. Just do a Clomid or gonadotropin cycle with intercourse or insemination. Absolutely true. But if those don’t work, you still get the ovarian benefit through this part of the IVF cycle.
Sperm issues. Here is where IVF (with or without ICSI) really shines. Historically, men with no or few sperm in their ejaculate were infertile. Men with weakly swimming or non-swimming sperm in their ejaculate were infertile. Period. Game over before IVF. Can IVF help? It depends on why there is no sperm in the ejaculate. If there is no sperm because the testicles can’t produce any sperm, then IVF or ICSI can’t help. We need to have some sperm to work with. (Of course if the male is willing to use donor sperm, then he doesn’t need IVF. Insemination of his partner with donor sperm should suffice unless his partner has female issues that require IVF.)
Methods to retrieve rare sperm, allowing their use with IVF/ICSI. If there is no sperm in the ejaculate because the sperm ducts are blocked, absent or only rare sperm are produced by the testicles, then IVF and ICSI can save the day. Because insemination occurs in a dish or via an injection needle, sperm really don’t have to be more than “present!” to get a shot at fertilizing an egg. Weakly swimming sperm can’t make it through the cervix, vagina, uterus and finally to the Fallopian tube to fertilize the egg after intercourse. Yet these same sperm might be able to get the deed done in the dish because frankly, they don’t have far to go. In some cases, sperm may be too few or too poor at swimming, so even traditional IVF won’t work. Molecular defects on either sperm or egg may inhibit sperm binding to the egg. Without binding, traditional IVF won’t work. In both these cases, ICSI can help.
Intracytoplasmic Sperm Injection (ICSI) for weakly moving, very rare sperm or non-binding sperm. If the technicians can get a handful of sperm that are alive, they can be injected one by one into the available eggs. Getting the sperm usually requires collaboration with a urologist who can remove sperm from the testicles or the epididymis (a sperm storage organ attached to each testicle). Sometimes the urologist will make an incision (under anesthesia) in the epididymis in areas that look rich for sperm under the microscope. Using a needle, he may aspirate the fluid that oozes from the tiny slit he makes in the epididymal tubes filled with sperm. This procedure is called microepididymal sperm aspiration (or MESA) . Another option is to remove a piece of testicular tissue, hand it off to the lab technicians who tease it apart strand by strand under the microscope and collect any sperm that ooze out (Testicular Sperm Extraction or TESE). The lowest tech option can be performed in the urologist’s office, using local anesthesia and a needle to aspirate fluid from the epididymis (Percutaneous Epididymal Sperm Aspiration or PESA). Find a urologist who specializes in fertility and works with your IVF team and (s)he should be able to advise you which approach will likely work best for your situation. Larry Lipshultz, MD, one of the leading male urologists specializing in infertility produced a information sheet for Resolve on “Alternatives available for sperm extraction”, that summarizes TESE, MESA and PESA.
What ICSI can NOT do.
- ICSI can not bring dead sperm back to life. Dead sperm will not fertilize an egg even if you inject the sperm into the egg. Non-moving sperm that are alive can be used but in my experience, our best results were achieved with sperm that have some motility, even if they are only weakly twitching.
- ICSI can not ensure that the “best” sperm gets the egg. The technician will use various visible criteria to pick the sperm. Sperm must look grossly normal (one normal sized head and one tail with no obvious deformities) and must give some evidence of being alive. More sophisticated selection methods exist to select for sperm but these are still handicapped by the starting material. If a male only has ten sperm that are recoverable and available for use, there is not much room to be too selective.
- ICSI does NOT GUARANTEE that the egg will be fertilized. Fertilization is not achieved by shoving the sperm into the egg. Both egg and sperm have to unwrap their respective DNA, have it combine in a new way to make a genetically unique human embryo, then get on with the embryonic program. Fertilization is such a complicated molecular process with so many steps you have to marvel that it ever works.
Fertilization in vitro. IVF was invented for women whose Fallopian tubes were blocked or missing. If your Fallopian tubes are blocked, the natural site of fertilization in the body is “Out of Order”. Fertilization can’t occur in other parts of the female tract like the vagina, cervix or uterus. Why not? Because fertilization and early embryo development require very specific conditions which only the tubes can provide. The success of IVF has steadily improved as lessons learned from animal research on the role of the oviducts (the name for animal Fallopian tubes) were applied to the development of better in vitro culture conditions for fertilization. Bypassing non-functional tubes is what IVF can do. So IVF is a must-have for women with no functional tubes.
Cryopreservation. Producing more embryos in vitro than could be safely transferred to the uterus is a problem caused by IVF that is “solved’ by developing technology to store excess embryos. Embryo cryopreservation methods are modifications of well established methods for freezing sperm that have been used for decades in the domestic animal industry. Cryopreservation of sperm, embryos and now eggs offers both men and women a chance to store their fertility for future use.
- Cryopresevation is handy for IVF patients who can look forward to a frozen embryo transfer cycle if the fresh cycle doesn’t work. It also increases the cost-effectiveness of the fresh cycle because the FET cycle is much cheaper.
- Cryopreservation is a boon to patients anticipating loss of fertility from cancer treatments.
- For women, whose reproductive shelf life or “use by date” is woefully short in our modern world, cryopreservation of eggs or embryos gives women a chance to delay parenthood for social reasons.
Cryopreservation does not improve the eggs or embryos. Usually, there is some damage from the process. At best, it causes no harm and restores the egg or embryo to its pre-frozen state.
IVF provides an opportunity to do genetic testing and choose which and how many embryos are given the chance to start a pregnancy. These choices don’t exist without IVF. Theoretically, IVF can be used to prevent higher order multiple pregnancies by only transferring one embryo. Genetic testing on the embryo before implantation is only possible through the “out of body development” that IVF provides. IVF with genetic testing is a way to optimize the chances for a healthy pregnancy and baby.
What IVF CAN NOT DO.
IVF can not reverse the genetic damage caused by aging. The eggs and sperm aren’t rejuvenated through IVF. IVF with aneuploidy testing can be used to avoid transferring chromosomally abnormal embryos but IVF can not repair aneuploidy in the original eggs or resulting embryos. IVF with genetic testing can detect abnormal embryos but that is a cold comfort to the patient if testing confirms that all the embryos are abnormal due to genetic damage caused by aging. IVF does open up the option of using donor eggs with a partner’s (or donor) sperm and carrying the resulting embryo to term, allowing older women without functional eggs the chance to experience pregnancy and motherhood.
IVF can not order up the perfect child. Each of us carries a genetic load of mutations or genetic traits that ensure that our children are not genetically perfect. When we combine our genes with our partner’s genes, we roll the genetic dice and open up even new possibilities for genetic mayhem and new mutations that can result in desirable or undesirable traits. Even if we put aside the ethical reasons for not pursuing genetic “perfection”, I don’t believe we can even define perfection, let alone achieve it. We humans don’t start out with perfect genomes so how can we select for perfection? The very messiness of our human genome is probably essential for adapting to our changing environment. The price we pay for useful genetic variability is non-desirable traits and harmful mutations.
The traits we want to see in our kids are complex and rely on a cascade of both genetic and environmental factors all lined up. The best we can do using IVF is try to optimize conditions for a healthy child. Perfection? Ask any mother and she’ll tell you her child is perfect so we are already there.
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