Mini IVF – A Blessing or a Curse?
There can be little doubt that aside from a woman’s age, the method used for ovarian stimulation represents the most important determinant of egg/embryo quality and outcome. There is no single stimulation protocol that is suitable for all IVF patients. It must be individualized…. especially when it comes to older women and women with diminished ovarian reserve (DOR), who tend to over-produce ovarian testosterone with potentially detrimental effects on egg quality.
Mini-IVF is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene and letrozole) under the premise that it is a safer and less expensive than conventional gonadotropin stimulation regimes, while yielding comparable success…. In fact, nothing could be further from the truth. The fact is that success rates with mini-IVF range between 10% and 15% per cycle (i.e., less than half the reported national average for conventional IVF). Moreover, when it comes to the use of Mini-IVF in older women and those with diminished ovarian reserve, by reducing the number of mature eggs per egg retrieval and failing to adequately down- regulate Luteinizing Hormone (LH) -induced ovarian testosterone, this approach can have detrimental consequences.
So let us examine the validity of the claims made in support of mini-IVF:
1. Milder stimulation using oral agents such as clomiphene or letrozole (alone or in combination with low dose gonadotropins) reduces stress on the ovaries and overall risks associated with IVF. This argument does indeed hold some water, but only as applied to mini-IVF in younger women who also have normal ovarian reserve. You see, older women and those who have DOR often have increased production of LH-induced ovarian testosterone, which can be harmful to developing eggs. Since both clomiphene and letrozole increase pituitary LH and thus ovarian testosterone, its use in older women can (in my opinion) prejudice outcome.
2. Women with DOR will respond better to “milder stimulation” and egg quality will so be enhanced. This assertion borders on the ridiculous. It is like saying “applying less force to a heavier object will increase the likelihood of moving it.” That is simply not how FSH stimulates follicle development. You see, the cell membranes that envelop the granulosa cells that line the inside surface of ovarian follicles have a finite number of FSH receptors on their surfaces. FSH molecules in the blood then attach to these receptors and mediate intracellular events that lead to granulosa cell proliferation, the production of estradiol, and the development of the egg (ovogenesis) which is attached to the inner wall of the follicle. Once all the receptors on these cell membranes are saturated, any residual FSH is discarded. This is why, when it comes to older women and women with DOR whose granulosa cell membranes harbor fewer FSH receptors, it is not possible to overstimulate them. Excessive FSH will simply be rejected and rendered inert.
3. Use of fewer drugs translates into lower cost. This would be true, were it not for the fact that success rates with mini-IVF across the board are much lower than with conventional ovarian stimulation. More important is the fact that the cost of IVF should be expressed in terms of the cost of having a baby…and not as the cost per cycle of treatment. When this is taken into account, the cost associated with mini-IVF will be found to be significantly higher than conventional IVF. Then there is the very real additional emotional cost associated with a much higher failure rate with mini-IVF.
4. Mini-IVF is less technology driven, less stressful and easier to execute. This is absolutely nonsensical. Aside from reduced cost of medications, the same monitoring and laboratory procedures are needed for mini-IVF as with conventional treatment.
I do not advocate over-aggressively stimulating younger IVF patients who have normal or increased ovarian reserve (as assessed by basal FSH, AMH and estradiol) simply to try and access more eggs. Indeed, such an approach is neither safe nor acceptable. In fact, when it comes to such women, it is often wiser to use low dosage stimulation to avert the development of ovarian hyperstimulation which, aside from putting the woman at risk, can also compromise egg/embryo quality. However, it is my belief that the prudent use of injectable gonadotropins rather than oral agents such as clomiphene or letrozole is by far preferable when it comes to optimizing both egg/embryo development and IVF outcome. This approach is referred to as Micro-IVF.