If you are considering IVF, Mini-IVF may be an effective, less expensive, less uncomfortable, and more convenient option. This is especially true if you are above age 37, if male or tubal factor are the only reasons for your infertility, or if age or decreased ovarian reserve is the primary reason for your infertility.
Before elaborating on the preceding statement, it is useful to explain what is meant by Mini-IVF. Mini-IVF is an abbreviation for minimal stimulation IVF. Similarly, Mini-stim IVF is another term for minimal stimulation IVF. Mini-stim IVF is the term we use in our practice to describe our version of minimal stimulation IVF. Minimal stimulation IVF is a successor to Natural cycle IVF. It is more successful than Natural cycle IVF and has a lower cancellation rate. The philosophy behind all variants of these minimal stimulation cycles is that less ovarian stimulation is more likely to produce higher quality eggs on average than a higher level of ovarian stimulation. Minimal stimulation IVF cycles use some stimulation of the ovaries, unlike Natural cycle IVF, but much less than traditional IVF (especially in the setting of older patients). Ovarian stimulation for minimal stimulation IVF may utilize the oral medications clomiphene or letrozole. Alternatively, 75 to 150 units of gonadotropins may be used and sometimes both oral medications and low dose gonadotropins are used. A GnRH antagonist may also be used to prevent something called an LH surge. Programs also vary in their use of ICSI (injecting sperm directly into eggs) or insemination (placing sperm is a dish containing the eggs for spontaneous fertilization). Programs may also approach egg retrievals differently with respect to the amount of anesthesia they use during the egg retrieval and their use of follicle flushing to enhance the chance of obtaining an egg from each follicle.
With traditional IVF, a woman undertakes an ovulation induction with gonadotropin medications to make as many eggs mature in her ovaries as possible before they are harvested from her. Gonadotropins are generally taken twice a day at a daily dose of 225 to 600 units per day for 9 to 12 days. Progress is monitored with transvaginal ultrasounds either daily or every other day until the ovaries are optimal for egg harvesting.
The scientific basis for minimal stimulation IVF is less well established than we would like it to be. There are no randomized comparisons of any minimal stimulation IVF protocol to traditional IVF as done in the United States. (IVF is likely done more aggressively in the United States than in Europe and the pregnancy rates are higher.) The most compelling study supporting a scientific basis for minimal stimulation IVF was done in the Netherlands by the Fauser group. This impressive study randomized young women to a higher or lower dose gonadotropin ovulation induction prior to IVF. All embryos produced were biopsied and PGD was done to determine which embryos were likely chromosomally normal. Fauser found that the higher dose gonadotropin group produced more eggs and more embryos, but the number of chromosomally normal embryos was the same in both groups.
Using markedly fewer expensive medications clearly saves money and decreases patient discomfort. Shortening the time of the ovulation induction and decreasing the amount of required monitoring saves money and increases patient convenience. Having fewer eggs and embryos in the laboratory (by eliminating some abnormal embryos), saves time for highly trained embryologists which can be passed on to the patient as a financial saving.
Since these are all great benefits of Mini-IVF, one may ask why Mini-IVF has not replaced traditional IVF. There is a trade-off in choosing to do Mini-IVF. The pregnancy rate per cycle is lower with Mini-IVF than it is with traditional IVF. The best available data that can be used to determine the decrease in pregnancy rates with Mini-IVF compared to traditional IVF was published by Teramoto. He reported on more than 40,000 Mini-IVF cycles done in his program in Japan. The pregnancy results were age stratified. The take home baby rate was slightly higher than half the average take-home baby rate in the nationally reported United States data for younger women. For older women, the take home baby rate was similar to the average success reported in the United States.
Most reproductive endocrinologist would agree that it is best for the patient to use the lowest dose of gonadotropins that provides a good result for the patient. However, patient’s responses to gonadotropins vary from each other and even vary from their prior cycle responses at times. Mini-stim approaches use a fixed low dose protocol and thus the thinking is somewhat different from a physician trying to target the lowest effective dose.
Some physicians are reluctant to use a therapy that is less effective than the best that is available. They worry that a couple has the capacity to do IVF only a certain number of times and they need to choose an approach that has the highest probability of working. The same medical codes are used in Mini-IVF as in traditional IVF and if patients have insurance coverage for a certain number of cycles of IVF, traditional IVF may be a best first choice for advanced therapy. However the situation for patients who are self-pay is less clear.
For younger patients, the cost of Mini-IVF is one-third to one-half of the cost of a traditional IVF cycle. The pregnancy rate is about half of what they would have with traditional IVF. The cycle is simpler, more comfortable and more convenient than traditional IVF. If a couple’s problems are well defined and not egg related, then Mini-IVF may be a good first choice for advanced therapy. For example, if the couple has male factor and the program’s approach to Mini-IVF includes ICSI, the male factor will be completely eliminated as a problem. The situation is similar for egg pick-up or tubal/ovarian adhesion problems. In these settings, Mini-IVF is significantly more effective than IUI even if gonadotropins are used. On average, it would be more cost effective for self-pay patients to go this route rather than use gonadotropins with IUIs.
For older patients, the cost of Mini-IVF is about one-third of a traditional IVF cycle. For traditional IVF, we will usually use 450-600 Units of gonadotropins/day for about 12 days. For Mini-stim IVF, we will usually use 75 Units of gonadotropins/day for about 6 days. The cost saving involved in reducing the 7200 units of gonadotropins used for traditional IVF to 450 units typically used for Mini-stim IVF is about $5,400 by itself. Many older patients will produce at most five embryos with traditional IVF. Most Mini-stim IVF patients will produce one or two embryos. Based on the Teramoto results, we would expect about the same pregnancy rate per cycle with either therapy for this age group, but the Mini-stim approach will cost one-third as much (if self-pay).
Financial issues aside, we would recommend traditional IVF as the initial therapy in patients with early decreased ovarian reserve. These are typically mid-thirty aged patients, but also may be younger patients who have a low normal antral follicle count (AFC) by our initial ultrasound exam. Any patient requiring complicated IVF, for example using PGD or TESE, should use a traditional IVF approach. Patients with limited access to their ovaries, for example, severe obesity, large endometrioma, or a fixed ovary behind the uterus, will do better with a traditional IVF cycle than with a Mini-stim IVF cycle. Patients, who fail to get pregnant after a reasonable number of tries of Mini-stim IVF, should move to traditional IVF. The number of tries that is reasonable needs to be an individualized decision, but for our program, it is usually three.
The cost of specialty infertility care is a major problem for many patients. Even when traditional IVF is the best approach, Mini-stim IVF may still be a valuable option and the only feasible option because of cost. Many patients have insurance coverage for IUI, but not for IVF. If pregnancy with IUI is at all reasonable, a limited number of IUI cycles should first be undertaken. However, if a couple does not have insurance coverage for IUI, a more cost efficient way of achieving pregnancy may be Mini-stim IVF.
It is hard to find IVF centers that are experienced with Mini-IVF, since Mini-IVF is not just traditional IVF using a slightly lower gonadotropin dose. The required National data reporting for IVF collects no information about Mini-IVF and Mini-IVF cycles are included in the total of IVF cycles for that program. (Since Mini-IVF is less effective than IVF, the data collection should show a lower pregnancy rate for that program.) We manage patients at times who live some distance from our program because they cannot find an IVF clinic nearby that has developed an interest in providing this type of IVF cycle. This situation will only change if patients request this type of therapy from the IVF clinics they are currently using.
We summarize the advantages of Mini-stim IVF compared to traditional IVF. These advantages are all patient-centered and also provide strong reasons why IVF centers may wish to offer this therapy.
• Mini- IVF is vastly easier for the patient to do than traditional IVF.
• Mini-IVF generally costs a third to half as much as IVF (including the cost of medications).
• IVM uses minimal medications. Fewer drugs are involved than in many IUI cycles.
• Minimal injections of medications required.
• Minimal blood tests are required. For most of our cycles, we monitor strictly by ultrasound.
• There are very few office visits required. For most of our cycles, there are two office visits on weekends and then office visits for the egg retrieval and embryo transfer.
• There are few side effects associated with these cycles. The risk of severe ovarian hyperstimulation is nearly eliminated.
• The risk of high order multiple births is minimal. We usually produce one or two embryos and transfer at most two embryos.