The Stumbling Blocks to IVF -- G. David Adamson, MD -- 09/25/02
By G. David Adamson
For some couples, IVF (in vitro fertilization) may be a treatment option for infertility. What is involved in IVF? How well does it work, and what are the risks? As part of National Infertility Awareness Week, WebMD joined with RESOLVE: The National Infertility Association to bring you the Trying to Conceive Cyber Conference. G. David Adamson, MD, joined us to discuss the stumbling blocks to IVF.
The opinions expressed herein are the guest's alone and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.
Member: What are the success rates you have experienced performing IVF in a 35-year-old patient with a unicornate uterus with LPD? Would the success rate of IVF for me decrease from 35-40 range due to my diagnosis?
Adamson: IVF success rates have improved dramatically in the last decade and can be used to treat most conditions causing infertility. But two major problems IVF does not treat well are advanced age of the female and significant uterine problems. At age 35, the live birth rate should be approximately 30% to 35%.
However, the live birth rate for a woman with a unicornate uterus (which means that only one half of the uterus has developed normally) could be significantly reduced because of complications of pregnancy, such as a pregnancy loss in the second trimester, or a premature delivery.
Nevertheless, if the patient has excellent OB care and can manage to obtain a great deal of bed rest during pregnancy, the chances for a live birth can probably be quite reasonable -- in the range of 15% to 30%.
It would be very important to try to avoid a multiple pregnancy with extra demands on the uterus and increase the risk of having a premature delivery.
Member: I am 44 years old. Have been TTC for over four years. We both have been tested and are healthy, so we have unexplained infertility. I was told I have old eggs. Should we consider IVF?
Adamson: The biggest and most difficult problem that most IVF doctors face daily is trying to help the couple in whom the woman is older than age 40. This situation occurs because in humans the natural reduction in fertility that occurs over time increases dramatically around age 40. For most women age 44 the chance that a single cycle of IVF will result in a live birth is well under 5%. Therefore, IVF is rarely performed in 44-year-old women because it's rarely successful.
The best options to try to deal with this unfortunate situation is to use donor eggs from a younger woman, in which case the live birth rate would be 40% to 60% on one attempt. Or consider adoption, which has a very high chance of being successful for most couples. The couple can also consider child-free living.
Member: I am TTC at 38. Have gone through 2 cycles of Clomid with an hCG shot and IUI. Have gone through one cycle of Follistim with hCG shot and IUI. My husband has below average count and motility. Do you think we should be more aggressive and go to IVF next?
Adamson: I would say, in a situation like this, it's important that the couple see an infertility specialist who can evaluate the subtleties of their clinical situation and explain to them their different choices -- what the chances are, and what the costs are.
Generally speaking, for a 38-year-old woman who has not conceived after three cycles of ovarian stimulation and IUI and who has some compromise of sperm quality, IVF would be the recommended treatment. However, it's important to make this decision after a comprehensive consultation with an infertility specialist.
Member: I took estrogen shots during IVF, had three high-quality eggs transferred but the previously too-thin lining wasn't checked on transfer day. I registered PG (low hCG) and it failed. Should the lining have been checked on transfer day? After that I bled little flakes/clots -- could there be immunity issues, too?
Adamson: It is unfortunate that you became pregnant with what's called a biochemical pregnancy and had a miscarriage, but this is a relatively common outcome of IVF, occurring in probably about 15% of patients. Usually, we can obtain more than three eggs during an IVF cycle, but in older women, three eggs might be all we can obtain.
The issue of the endometrium thickness is very complicated. It is appropriate to measure the endometrial thickness during the IVF cycle, and we usually measure the endometrial thickness at time of egg retrieval. However, it is not possible at the time of egg retrieval to change the endometrial thickness. Most IVF clinics do give progesterone supplements after the embryo transfer.
Generally speaking, the endometrium is thought to be adequate if it is 7 or 8 mm in thickness. However, some women certainly conceive or get pregnant and deliver a healthy baby with an endometrium thinner than 7 or 8 mm. Currently there are no scientifically proven ways that will "cure" an endometrium that cannot be developed to 7 or 8 mm in thickness.
The usual approach is to increase stimulation drugs so that the woman will have higher estradiol levels and as a result a thicker endometrium. There are no scientific data or studies which prove that immunological problems cause a thinner endometrium or a "receptivity" problem, or that any immune treatment is effective in solving this problem. However, a great deal of research is being done in this area, and hopefully in the next few years we will have better answers for this problem.
It's important to note that endometrium problems are very uncommon with probably only 2% or 3% of women having any clinically significant difficulty in developing adequate endometrial thickness.
Member: I'm told I have isthmic synechiae and left cornual blockage. What does this mean, and is IVF my best option? I'm 29.
Adamson: Isthmic synechiae and left cornual obstruction. This problem means that the woman has scarring or adhesions in the fallopian tube near the uterus. Before we had IVF this problem would be treated with a laparotomy and tubal surgery. Success rates with this surgery were approximately 20% to 40% over a two- to three-year period.
Approximately 10 years ago, another surgical method or treatment involved passing catheters through the uterus using a hysteroscope (A small telescope placed through the cervix into uterus) and the catheter was then passed into the fallopian tube to break down the scar tissue and make an opening. However this "tubal cannulation" procedure is usually only successful in women who have only a small amount of damage in the isthmic or narrow part of the fallopian tube near the uterus.
Since there is often additional scarring farther out in the fallopian tube, tubal cannulation is often not successful. The risk of ectopic or tubal pregnancy would still be high (10% to 30%). So for most women age 29 with this condition, IVF would be the preferred treatment with live birth rates of approximately 40%.
Member: How many eggs are considered a good amount when doing a retrieval?
Adamson: The number of eggs retrieved varies greatly from woman to woman and is primary dependent on the age of the woman. The average number of eggs retrieved is about 10 to 12 eggs for each retrieval.
It's important to understand we generally do not get an egg from every follicle seen on the ultrasound. Most women have 15 to 20 follicles of varying sizes in order to collect 10 to 12 eggs. Also, not all eggs retrieved will be of appropriate maturity --some too mature and some immature.
In addition, not all of the mature eggs will fertilize with the sperm. And not all eggs that fertilize will be genetically normal, nor will they develop into normal embryos.
Therefore, even if we retrieve an average of 10 to 12 eggs, we usually will end up with only four to eight or possibly fewer normally developing embryos.
Member: We have had four failed IVF attempts. Stimulation has always produced between 25-12 eggs at retrieval. However, fertilization yields have been low. Are there any documented cases where stimulation affects the quality of the eggs?
Adamson: This is a very good but difficult question. If stimulation has been good enough to result in 12 eggs on average in four cycles, we would generally consider that this person has a normal response for ovarian stimulation. With just that information, we know that pregnancy rates with IVF would likely continue to increase for another 2 or 3 cycles.
However, one of the advantages of doing IVF is we obtain additional information about eggs and embryos. Where fertilization rates are low, this suggests there is either a problem with the sperm fertilizing the egg or a problem with the eggs themselves.
Sperm problems can almost always be treated effectively with intracytoplasmic sperm injection (ICSI). Therefore, I would expect in this situation that ICSI is probably being performed because of a possible sperm problem. If ICSI has not been performed, that would be recommended.
However, if ICSI has been performed and fertilization rates are still low, then we would generally conclude the reason for the low rate is a reduction in egg quality. This may be associated with the woman's age or some other unknown problem that is not diagnosable in the year 2002.
The decision as to whether to proceed with more IVF would depend on the apparent quality of the embryos and their development. If embryo development has appeared normal, it might be reasonable to attempt one or two more cycles, having drawn the conclusion there is still a reasonable chance for pregnancy. But if embryo development has also not been good or if eggs appear abnormal, there is a high likelihood the chances for pregnancy are very low.
In this case, the alternatives to consider would be the use of donor eggs, adoption, or child-free living.
Member: There have been some recent studies that suggest having endometriosis greatly reduces the success rates of IVF. What do you do differently for those patients to help improve their odds?
Adamson: This is also a complicated question. Large amounts of patients undergoing IVF with a diagnosis of endometriosis are similar to patients who do not have endometriosis. However, there have been smaller studies that have identified groups of patients with endometriosis who appear to have much lower success rates with IVF. In particular, women who have had endometriosis in the ovaries (endometriomas) may have a poorer response to the ovarian stimulation drugs, get fewer embryos, and have a lower success rate.
However, if the response to ovarian stimulation drugs is good, even with endometriomas in the ovaries, pregnancy rates for those patients may be just as good as someone without endometriosis.
Women who have had surgery to remove endometriomas from ovaries lose some ovarian tissue and invariably also get some scarring in and around the ovaries. This can reduce blood supply to the ovary and result in a lesser response to ovarian stimulation drugs. In these situations, there are fewer eggs, fewer embryos, and sometimes lower pregnancy rates.
Other studies show women with endometriosis may have reduced egg quality when compared with women without endometriosis. Also, while there is still a little controversy about this, most physicians feel that miscarriage rates are not higher in women with endometriosis.
In terms of treatment, therefore, each patient must have individualized care. If there is a large endometrioma, it is often appropriate to remove the endometrioma before IVF. Additionally some good studies have shown that ovarian suppression using GnRH agonists (Lupron, Synarel) improves pregnancy rates in women who have severe endometriosis.
And suppression and ovarian suppression for four to 12 weeks before IVF is also likely to be helpful.
Finally, it is important that women who have endometriosis try to avoid multiple surgeries on their ovaries, or removal of an ovary, because this reduces the total number of eggs available for attempting pregnancy.
Member: How do you decide on an IVF doctor? It seems like they each feel their protocol delivers the best success rates.
Adamson: There are many good IVF programs in the U.S. As a former president for the Society for Assisted Reproductive Technology (SART), I firmly believe that patients should go to clinics that belong to SART. SART requires high training standards for their physicians, onsite laboratory inspections, and recommends practice guidelines for their members. You can find out if your physician belongs to SART by going to ASRM.org.
Additionally, patients can review the CDC and SART and RESOLVE annual reports of clinic success rates. It is essential to understand that direct comparisons of clinics is not possible because of differences in patient selection and protocols. However, patients can determine whether clinics near them provide the services in which they are interested and has success rates around the average or better.
I also believe that patients should be aware of the practice guidelines recommended by SART and avoid physicians who recommend expensive and experimental treatments that are not recognized as clinically applicable. Such treatments -- for example, immunotherapy -- should only be undertaken in a formally approved research study that does not cost the patient large amounts of money. If no one else is doing it, and it sounds too good to be true, it's likely worth avoiding.
Member: How many failed IVF attempts should one have before "enough is considered enough" and options such as adoption and/or donor eggs should be considered?
Adamson: The number of IVF cycles that a patient should undertake can vary from one to approximately six or seven. The wide variation occurs because with IVF we learn a lot about the sperm, eggs, and embryos of the patient. If we learn on the first cycle that egg and embryo quality is poor, then very often it's not reasonable to try a second cycle.
However, if the patient responds well to ovarian stimulation and makes healthy embryos, there is data showing that live birth rates will continue to increase without much reduction in per-cycle success rate through six or seven cycles.
Clearly there are not many couples who can afford the financial or emotional costs of doing this many cycles. For most patients, approximately four cycles that are unsuccessful is the most that they do.
Moderator: Unfortunately, we are out of time. Thanks to G. David Adamson, MD, for joining us today. For more information on IVF and other fertility issues, be sure to explore all the fertility info here at WebMD, including our message boards and live chats.
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