Home : IVM (in vitro maturation)
IVM: in vitro maturation
IVM is a variation of IVF which uses immature eggs removed from the ovaries without having to perform an ovulation induction to make those eggs mature in the body. The eggs are instead matured in the laboratory.
They are then fertilized, cultured and transferred as in routine IVF. Injectible medications to stimulate the ovaries are not generally used, which eliminates many side effects for the patient as well as decreasing the expense. IVM also eliminates the need for most of the ultrasound monitoring which is routine for IVF procedures. Blood tests to assess the progress of the ovulation induction are similarly eliminated, making the procedure more convenient and comfortable for the patient.
The History of IVM
In the normal menstrual cycle, an egg develops inside of a cyst or follicle over a two week period in response to gonadotrophin hormones that a woman produces. The follicle increases in diameter from about 2 mm to about 20 mm. The cells around the egg multiply over this time period and produce estrogen. The egg is firmly attached to the follicle wall until increased amounts of the hormone LH (or in medical cycles, HCG) induce enzymes that free the egg from the wall so that it is free floating in the fluid in the follicle. It can then leave the follicle after LH also induces enzymes to create a hole in the follicle. During this time, the egg increases very slightly in size and all of the chromosomes are contained in a membrane in the cytoplasm. With the increase in LH as a trigger, this membrane breaks down and the egg divides the chromosomes into two equal groups and moves one of these groups outside the egg (polar body). An egg that has done this is referred to as a mature egg (or MII). In the natural cycle, the egg, which has been freed from the follicle, is then picked up by the end of one of the fallopian tubes. If the egg is lucky enough to be fertilized, it again divides the chromosomes into two equal groups and pushes one of them outside the egg.
In 1935, it was observed that if rabbit eggs were removed from their follicles, some of them would spontaneously mature. In 1965, Edwards (one of the original scientists responsible for the first baby born from IVF) showed that the same thing occurred for human eggs. The first baby born from IVF, Louise Brown, was not born until 1978. The first baby born through IVM was reported in 1991. The first planned IVM pregnancy in North America was achieved by the McGill program in 1999. Initially, the process of IVM was far from being as efficient as IVF. A commercial media for egg maturation is now available and the details that enable pregnancies to occur at a reasonable rate in appropriately selected patients have also been worked out. The exact limits of IVM are far from agreed upon, but IVM (and its variations) is clearly another tool that can be used to help some patients achieve pregnancy.
Advantages of IVM compared to traditional IVF
1. Simplicity
The procedure does not require any medications to stimulate the ovaries (see variations on IVM for some exceptions). The IVM procedure eliminates the need for injectable medications to suppress a patient's endogenous (own) gonadotropin production such as Lupron, Ganirelix. or Cetrotide. It also eliminates the need for the gonadotropin medications that cause the immature eggs to develop within follicles and mature. For example, these are medications include Follistim, Gonal F, Bravelle, Menopur, and Repronex. For most patients, this is the most complex part of IVF. Patients find the process of injecting themselves with multiple different medications several times a day to be highly stressful. For the process to work well, they need to take the correct medication in the correct amount (which may change daily). Many patients start the IVF process fearful of taking injections. Some never learn to do the injections by themselves and need to coordinate their injection schedule with their friend or partner. By not using these medications, the complex monitoring required for IVF is no longer needed.
2. Time Saving
In IVF, the patient is frequently monitored with ultrasound exams and blood tests to optimize the development of follicles (containing eggs) in the ovaries. This monitoring process usually takes 10 to 14 days and requires a number of office visits that are necessary to guide the ovulation induction. For the patient, this requires missed time from work or school. For IVM, in our program, we use one or two ultrasound exams and no blood tests. For IVF situations where the plan is to transfer embryos either into a different person for the same person at at a future times (e.g., if a sister living a distance away is to be an egg donor or a breast cancer patient storing eggs for her future use), the patient obviously needs to be there for the egg retrieval and these procedures may be scheduled over a long weekend.
3. Less Painful
Eliminating most medication injections and eliminating all blood tests clearly decreases patient discomfort with IVM compared to IVF. Almost all patients handle these discomforts with IVF as a necessary component of the process, but they are still unpleasant.
Generally, the patients who have the most discomfort after an egg retrieval are those with a large number of eggs, a PCO (polycystic ovary) pattern in their ovaries, or a PCOS (polycystic ovarian syndrome) diagnosis. (These types of patients also have the most success with IVM.) Because the medications we use in IVF hyperstimulate the ovaries, these patients may have swelling of pelvic tissues and loss of fluid into their abdomen (ascites). Some experience this for a day or two, but rare patients may experience it for several weeks. There is NO risk of ovarian hyperstimulation syndrome with (programmed) IVM.
Even patients without potential for ovarian hyperstimulation, are likely to experience less recovery pain after the egg retrieval procedure. Because the cysts we obtain the eggs from in IVM are much smaller then for IVF, a smaller needle has to be used. This usually results in less discomfort after the procedure.
4. Lower Cost
IVM patients should have significant savings by not using many injectable medications and eliminating most of the monitoring of a normal IVF cycle. In our program, we estimate that most self-pay patients will save about 50% of the total cost of a traditional IVF cycle. For some patients, IVM will offer them the opportunity to do an IVF variant cycle when they could not afford a traditional IVF cycle. Patients may realize additional savings if they choose to use our IVM multi-cycle discount program.
Since IVM used ICSI, it can be used to overcome male factor problems. If male factor is part of the reason that pregnancy is not occurring, IVM may be the most cost effective approach.
5. Theoretical Egg Advantages
Eggs produced in IVM cycles are more similar to each other in appearance than eggs produced in IVF cycles. For example, eggs from older patients sometimes have a dark cytoplasm after the ovulation which requires high doses of medications with routine IVF. With IVM, eggs from such patients generally have a normal appearing cytoplasm. There is limited and contradictory information in the medical literature comparing quality of eggs obtained from IVF compared to IVM in the same patient. One especially provocative study, suggests that chromosomal abnormalities (which are created at the time of HCG or at the time of fertilization) of eggs is reduced with IVM. (Earlier studies suggested that chromosomal abnormalities were increased, but they largely used eggs that were still immature after a routine IVF gonadotropin stimulation which was a reason for their being abnormal).
Disadvantages of IVM compared to traditional IVF
1. Limited Use
Perhaps 2000 babies have been born world-wide from IVM. This compares to more than one million born with IVF (57 thousand in the United States alone in 2007). There are only a few programs in the United States which offer IVM. There are over 430 IVF programs in the United States. In terms of safety and knowledge about the long term impact of the getting pregnant process on the resulting children, we can be more assured about the safety of IVF than IVM. There are a number of small studies that compare the safety of IVM to IVF within programs and find no safety problems. For example, McGill University has followed this issue over the ten years (with about 200 babies) they have been doing IVM and have not found any problems. Although I am not concerned about the safety of IVM, one can never prove safety in any absolute way, but the greater our experience with a procedure, the more comfortable we are with it and have a greater basis for reassuring patients about its safety.
Most practitioners consider IVM to be a minor variant of IVF since once the eggs have matured in the laboratory, all the same things are done with them as with IVF. By this reasoning, the same safety data should apply to both IVF and IVM. However, there are clearly differences in the eggs and embryos produced in this procedure. There is an informal registry for IVM babies to look for problems if they were to exist at McGill University.
2. Limited Clinical Data
Because of the widespread use of IVF and the limited use of IVM, the medical literature about these procedures is not comparable. Most management decisions for IVM are taken from what we know from IVF. Protocols for IVM are still at an early stage of evolution and it is easy to ask clinical questions that have no answers in the medical literature. Current approaches are very dependent on the clinician in charge, their understanding of the IVM and IVF literature, and their clinical experience.
3. Pregnancy Rates
The IVM literature suggests a pregnancy rate slightly below that for routine IVF to a rate about that of IVF (25-35%). The primary variable in the IVM literature that predicts success is the number of eggs retrieved. The best candidates for IVM are those young patients with a PCO pattern in their ovaries. These are also the best candidates for IVF and have the highest pregnancy rates as a group. Age is a key predictor of success with IVF and is also likely to be one for IVM. There is limited data on IVM in older patients or in non-PCO patients. Unfortunately, the CDC/SART national data collection of IVF success rates of programs in the United States does not distinguish between IVF and IVM in its data collection. This means that the government generated data on pregnancy rates from different programs is a mixture of the pregnancy rates for IVF and IVM (if they have IVM).
(We have provided information on our IVM pregnancy rates annually since the start of our program.)
4. Cycle Cancellation
Although IVM can clearly result in babies, it takes a lot of eggs to get there. Eggs are harder to get during the retrieval that with IVF. In IVF, the eggs are free floating in the follicle. In IVM, they are attached to the follicle wall and have to be dislodged during the retrieval (which takes much longer). It there are not many antral follicles, few eggs are likely to be retrieved. A good maturation rate is 40-50%, so you need a good number of eggs to have any to work with. A good fertilization rate is 70% (similar to routine IVF). These factors lead to an increased potential for cycle cancellation in patients who do not have a PCO pattern in their ovaries.
5. Program Selection
Although there are important differences between IVF programs in patient management, these differences are much smaller than the different variants of IVM. Over the years, a network of information on IVF programs has evolved. The CDC/SART database serves as a tool that patients can use to begin evaluating programs. There is little similar information to help patients select programs for IVM.