IVF OVERVIEW By Tracy Telles, M.D. Dr. Hendler: Hello and welcome to KP Healthcast. I m your host Dr. Peter Hendler and today our guest is Dr. Tracy Telles. Dr. Telles is an IVF physician in Kaiser Walnut Creek and she has been with Kaiser since 2004. Welcome. Dr. Telles: Thank you. Great to be here. Dr. Hendler: Dr. Telles, tell us a little bit about yourself. Dr. Telles: So, I did my OB/GYN training in Phoenix. At that time, I decided I wanted to specialize in infertility treatments so I did a fellowship in reproductive endocrinology and I did that at Stanford. After I finished, I decided I wanted to go work at UCSF. I was there for three years on faculty doing IVF as well as teaching medical students and residents. Dr. Hendler: You can t get two better schools than that. Dr. Telles: Thank you. Dr. Hendler: Let s start just by explaining what in vitro fertilization is. Dr. Telles: So in vitro fertilization or what we call IVF is the process where the patient takes hormones that stimulate her ovaries to produce several eggs. The number of eggs is variable depending on the patient s age. Those eggs are then removed at some point from the body in a procedure that we call an egg retrieval or a harvest. We then fertilize those eggs outside of the body. There are a couple of different ways to do that. One is to mix them sort of more naturally with sperm, what we call standard IVF or sometimes, we can directly inject a sperm into an egg. We call that intracytoplasmic sperm injection or ICSI. Either of those methods will generate embryos. We then grow those embryos in a dish for several days and at some point, we transfer our implant embryos back into the patient s uterus in a procedure that we call an embryo transfer. Dr. Hendler: What are some reasons why a patient might need to use in vitro fertilization? Dr. Telles: Most patients who do IVF have tried other fertility treatments that just have not been successful. Repeated insemination failures is probably the most common reason. There are some other medical issues that can be present where IVF is literally the Page 1
only treatment that would work. Two examples of that would be if a woman has blocked fallopian tubes either from surgery or infection, then IVF would be the only way to bypass that blockage. Another reason would be severe male factor infertility where we see a very, very low sperm counts or sometimes even 0 in a sample. In those cases, we definitely need to take out the egg so that we can directly inject a sperm into an egg. Dr. Hendler: Can you tell us something about the process? How does a patient get started with IVF? Dr. Telles: First we do an initial consultation and that s done where we establish that the patient is a candidate for IVF. Once that s determined, we then establish a protocol or almost like a recipe that we need to use to grow her eggs. In general, there are three common recipes that people use and there are reasons why we would pick one over the other for a given patient. Things would be like we look at her age, we look at hormone levels, we look at her ovarian stalk on ultrasounds something that we call antral follicle count. All of that information is integrated to help us decide on a protocol. Once that s done, then we kind of turn the case over to our IVF case managers. They are able to create what we call a calendar. A calendar is like directions for the patient to keep them organized as to what medications they need to take. In general, we say that an IVF cycle takes about two months to complete. It s not two complete months where we are seeing the patient every single day. There s sort of two very busy weeks in that two month period. The first is what we call a stimulation week. That s when we are doing repetitive ultrasounds. We re usually checking blood levels of certain hormones on those same ultrasound visits. That way we can track the growth of those follicles or eggs. The rule of thumb is that on average, it takes about ten to twelve days of medications to grow a person s eggs. We usually make the decision that it s time to take them out, based on those ultrasound findings as well as hormone levels. Then we kind of move into what we call the procedure week. That is the week where we anticipate that the eggs would be ready for harvest and we then take them out, and culture them in a dish. Sometime later in the week, we would then be transferring embryos into that patient s uterus. So it s usually anywhere from about 5 to 7 ultrasounds. Normally, we would do blood testing every day that we do an ultrasound and there s the two procedures, the retrieval and the embryo transfer. Dr. Hendler: Can you tell us about some of the risks associated with IVF? Dr. Telles: There are some very specific risks associated with the harvest. That would be things like bleeding, infection, injuring bowel or bladder because those things are very close to female reproductive organs, but in general, those risks are quite low. We are frequently asked about medications and if there are any risks with those. There are some concerns that repetitive exposures to these medications might increase some type of female reproductive cancers such as breast or ovarian cancer so we are very aware of that. Having said that, we feel that most patients are not exposed at levels that would increase their baseline risk for these cancers. Page 2
Another area of risk would be that with IVF we see increased risk of multiple gestations and the problem with those pregnancies and definitely problems for kids is highly associated with the number of babies that a patient is carrying at once. We would always prefer that a patient be pregnant with one baby at a time. For example, if somebody is carrying twins, her risk of going into labor early, her risk of breaking her bag of water early, her risk of hypertension, diabetes, all of those things are increased. The babies themselves could also be at increased risk if you deliver early. For example, the risk of cerebral palsy, seizures, developmental delays all of those things are increased if you are carrying more than one child at one time. For example, if you are carrying triplets, you are likely to deliver much earlier in pregnancy closer to 33 weeks. Just as a point of reference, 40 weeks is usually someone s due date is established. If you deliver triplets at 33 weeks, your risk of those things like cerebral palsy, seizures, developmental delay is increased over 30% whereas if you deliver at 40 weeks, it s less than 5%. So again, doctors feel one baby at a time really is the safest. Dr. Hendler: We hear so much about multiple gestations in IVF. How is that controlled? Does the patient decide how many embryos to put back or is that something the doctor decides? Dr. Telles: The American Society of Reproductive Medicine or ASRM is the professional body that oversees procedures like IVF. ASRM has guidelines that are intended to increase the chance of pregnancy without taking too great of a risk of multiple gestations. ASRM developed guidelines where recommendations have been made based on the patient s age and also on her previous fertility history. We definitely see a significant link between chance for success and female age. Kaiser is a member of ASRM and the Society of Assisted Reproductive Technology what we call SART. We adhere to those guidelines very closely. The physician basically gets a recommendation from the embryologist who assesses or grades embryos including the morphology or appearance. That grading looks at cell number. It looks at the symmetry of the cells, and helps to determine the potential of that embryo for causing a viable pregnancy. So the physician, the embryologist, the patient all discuss those things together. At some point, we come up with a recommendation. Dr. Hendler: Can you give us an overview then of all the IVF Services that Kaiser offers? Dr. Telles: We do all of the traditional things that are associated with IVF. There are some specific techniques that we can apply once we have eggs and sperm and embryos available for manipulation. One example would be ICSI. That is the intracytoplasmic sperm injection where we inject a single sperm directly into an egg to fertilize that egg. We want to do that when the male partner has abnormal sperm testing such as low sperm counts, abnormal shapes, abnormal motility which is how well they are moving. There are other clinical scenarios where we might want to use ICSI but that is the most common reason. Page 3
Another service would be assisted hatching. Assisted hatching is where embryos essentially grow in a shell for about the first week of life and then they literally hatch out of the shell. As we all get older, that shell gets harder and we can augment that hatching by weakening a part of that zona or shell so that the embryo has a little easier time getting out. That is called assisted hatching. In terms incubating embryos, we can cultures in our dishes up to day 6 after we have retrieved them. We perform embryo transfer usually on day 3. That is our default day. Some patients we transfer later, such as day 5 and others earlier such as day 2. We don t have a preferred day of transfer. We basically look at each individual patient and see how many embryos they have, what their embryo quality looks like and make a decision about the day of transfer based on how many embryos we plan on transferring for that person. Dr. Hendler: Can you talk a little bit about pre-implantation genetic diagnosis or PGD? Dr. Telles: PGD is another highly specialized lab intervention with embryos. It allows us to test embryos for certain genetic abnormalities before the implantation or pregnancy actually happens. Basically, we do IVF as usual and then once we have embryos, we biopsy one cell from that embryo and test it for certain genetic abnormalities. We do need to know exactly what we are looking for. If the patient has cystic fibrosis or hemophilia, that is a genetic abnormality that we can diagnose. We can see what embryos carry that abnormality and choose not to actually transfer those affected embryos. So only embryos that do not carry that abnormality would be candidates for an embryo transfer. It does add some cost to an IVF cycle because first we have to know what to look for, which means we have to be able to identify that abnormality, and then find a way to identify it in embryos. So we generate what are called markers. We have to create markers, do your IVF. The testing is done at an outside lab. Once we have our markers, we start an IVF process, do the biopsy, send the single cell off to an outside lab. The testing is done, the information is sent back to us from that outside lab so we know what embryos are available for transfer. Dr. Hendler: Can you give us some idea about the success rates with in vitro fertilization? Dr. Telles: Again, they are mostly based on female age. Success rates can be as high as 40 or 45% for young patients. They can be as low as 5% for patients in our older categories. Average statistics may not apply to an individual patient within that age group though because there might be various factors affecting her fertility such as decreased ovarian reserve, decreased numbers of developed good quality embryos. Most clinics report success rates to the CDC and to SART. That data is actually available for patients to review. So that is public information. You have to be careful comparing different clinics because patient populations might be different, treatment approaches might be different, some clinics might actually have restrictions as to who is allowed to Page 4
go through an IVF procedure. You can t always use that data to compare clinics but just as a general guideline, I think it s helpful information for patients. Here at Kaiser, we have consistently done really well since 2004, since we started. We are very proud to have contributed to the birth of over 600 kids to date. Dr. Hendler: How much should a patient expect to pay for an IVF cycle? Dr. Telles: We break the costs down into three separate areas. There are some basic costs that apply to everyone. That would be things like retrieval, transfer, ultrasounds, blood testing, universal costs. There are more specific costs that are for individual patient like medications. That can vary quite a bit depending on how much an individual patient needs. Then we look at lab costs. Certain patients might need some special laboratory interventions and that also can increase costs. So the basic cost of IVF without any special lab and if we were just looking at the ultrasounds and procedures would be about $9,500. The medications can vary anywhere between $2000 to as high as $6000. Additional labs can cost anywhere from $650 to $2,200. That is if you need something. There are patients who don t need any special interventions and their lab costs might literally be 0. An overall estimate if you include all three components would average between $11,000 and $16,000. One of the advantages of Kaiser is that patients can apply for financing through a third party and we work with that third party to allow them to finance the basic fee as well as lab fees. Typically, patients get their medications outside Kaiser at some special fertility medication pharmacies. That part is separate and is not allowed to be financed within Kaiser. Dr. Hendler: How about the concept of egg donation? How does that work? Dr. Telles: Candidates for egg donation are typically women who have had such suboptimal embryo quality that their chance for success with in vitro is exceedingly low. This usually is in older patients but it can be in patients who have a younger age but diminished ovarian reserves. Essentially their ovaries are acting older than their biologic or their chronologic age. We help these patients recruit a young, healthy donor. Usually we work with agencies and there are many agencies that we work with. The donor essentially goes through an IVF process and donates her eggs to the patient who then becomes what we call the recipient. The donor s eggs are combined with the recipient s husband s sperm and a pregnancy is genetically related towards the husband then and the donor. While that IVF is happening to that person, the recipient is taking medications that essentially prepare her uterus to receive those embryos. So there are these agencies who recruit young healthy people. They do some initial screening, look up medical history, reproductive history, family history. They make sure there are no glaring issues. If she passes that initial testing, then a more comprehensive level of screening is done. That would include things like drug screening, psychological screening. Things like that. Once she passes all of that, then she becomes available. Page 5
Once the patient selects that person as a donor, then I would meet with her, if the recipient was my patient. I would screen her further and we would insure that she is a good candidate. If she passes all our testing, then we essentially synchronize the donor s cycle with the recipient s cycle. Usually we use birth control pills to do that. Then we move on to the egg donation cycle. Dr. Hendler: How much more successful is that compared to using her own eggs? Dr. Telles: Egg donation is by far the most successful form of assisted reproductive technology that most clinics do. It really has the highest rate of success because basically you are doing an IVF on a person that is not infertile. Having said that, it is not perfect. It is not 100% successful because you can never predict exactly how people are going to react, what s going to happen with donors, how are they going to react to medications, but for the vast majority of patients, there is a substantial increase in success using an egg donor compared to IVF using her own eggs. Dr. Hendler: What about the cost difference for using egg donor cycles rather than routine IVF? Dr. Telles: The IVF itself is often a lot cheaper for the donor because she is not going to need the same level of medications that the recipient herself may have used in a previous cycle. But now the recipient is taking medicine so now we have to account for that. There is also the agency fee. A good estimate for an egg donor cycle is somewhere in the range of $25,000 to $30,000 if you include her medications for the donor, the IVF for the donor, her compensation for time. If you look at recipient s medications, the recipient s procedures which would be the embryo transfer, as well as fees to the agency that has coordinated the donor to be available to us. Dr. Hendler: So let s say a patient goes through standard IVF, but she doesn t get pregnant. Does she have to start all over again or do the patients have leftover embryos? Dr. Telles: Our normal procedure at Kaiser is to transfer an appropriate number of embryos for a given age, and we select the best quality based on grading by the embryologist. The embryos that are not transferred, we also grade those. If they reach a certain grade by a certain day on our culture dishes, then we can save them for future pregnancy attempt. But we only save those embryos that are good quality because those really are the only ones who would survive that freezing and thawing process which can be pretty traumatic for an embryo. If we are saving suboptimal embryos, when we thaw them, they are not going to survive, and therefore not result in pregnancy. So we only want to save those embryos that really have a very reasonable chance of actually causing future pregnancy. We can save them for long periods of time, weeks, months, years as long as people want us to save them. If a couple in the future decides they want to get pregnant again, baby #2, or possibly the first transfer actually didn t work, then we can do what is called a frozen embryo transfer cycle. In that we focus more on getting the uterus ready to receive embryos without actually stimulating the Page 6
ovaries so we don t need any retrieval. It is quite a bit cheaper. Again, only good quality embryos are saved though. For older patients, they often don t have leftovers because usually the best quality are transferred at the fresh cycle. Dr. Hendler: So are the success rates generally different for the frozen embryos than they are for the fresh embryos? Dr. Telles: I think it really depends on what you save. At Kaiser, we are fairly critical about what we save so we tend to have very good success rates. It depends on the quality of the embryo before it goes through the freezing and thawing process. As a rule of thumb, frozen embryo success rates are slightly lower than fresh. Again, one of the advantages of having frozen embryos is that the usage free, what we call the cycle fee, is quite a bit lower closer to the $3000 to $4000 range. So it is quite a bit cheaper to have another attempted pregnancy without having to go through the more expensive procedures. Dr. Hendler: Is IVF for Kaiser members only? Dr. Telles: Initially we were only offering IVF to Kaiser members. Now we have increased our embryology staffing, we have increased our support staffing and we have a couple of new physicians. IVF is now open to anyone in the community even if Kaiser is not your regular medical provider. Dr. Hendler: If you are a Kaiser member, is IVF covered by Kaiser? Dr. Telles: In terms of infertility services, coverage for diagnosis and treatment of infertility is quite variable and it really depends on a patient s individual plan. Some patients have more comprehensive coverage than others. With IVF in particular, it is possible it is a covered benefit, but for most patients, it is not part of their normal coverage. For those patients, IVF services would be provided on a fee for service basis. Dr. Hendler: If I were a patient interested in finding out more about IVF at Kaiser, what should I do? Dr. Telles: We have a web site, KPIVF.org and anyone can access that. That can give you contact information. The Kaiser Permanente Center for Reproductive Health is located in Fremont. It has an 800 number, 1-866-415-9621 or a local phone number 510-248-6900. There is more information that you can either get on the web site or by phone. We have satellite offices. Those are located in Santa Clara, Walnut Creek which is where I m at, and also San Francisco. All egg retrievals and embryo transfers are done at the IVF Center in Fremont. That is where the equipment is to incubate embryos and retrieve eggs, things like that. Patients are seen for initial consultation, testing, ultrasounds, etc., possibly in Fremont, and also in the satellite centers. When the patient is ready for their procedures, the patients and the satellite physicians would travel to Fremont to the IVF Center to actually perform the procedures. Also Sacramento has an IVF center and has a corresponding satellite office in Vacaville. They are also part of our web site, Page 7
www.kpivf.org, and they also would offer the same infertility services that Fremont offers. Dr. Hendler: Thank you very much for being here. Do you have any last thoughts or any final things to say? Dr. Telles: No, we look forward to helping as many patients as possible and we can t wait to see more patients. Dr. Hendler: Thank you very much. Dr. Telles: Thank you. Dr. Hendler: Many Kaiser Permanente members have coverage for the diagnosis and treatment of infertility and some members have coverage for in vitro fertilization. IVF is listed as a covered benefit in the evidence of coverage of the Kaiser Permanente Health Benefit Plan. Otherwise, services described are provided on a fee for service basis separated from and not covered under your Health Plan Benefits. Clinical Services are provided by providers or contractors of the Permanente Medical Group Incorporated, Kaiser Foundation Health Plan Incorporated, and Kaiser Foundation Hospitals. They receive compensation for providing facilities and other support in connection with these services. For specific information about your Health Plan Benefits, please see your Evidence of Coverage. Page 8