Aside from a woman’s age, the factor most heavily affecting egg/embryo quality in IVF is the method of ovarian stimulation used. There is no single stimulation protocol that is suitable for all IVF patients. Patients should not treated as if “one size fits all.” Each patient’s protocol for IVF stimulation must be individualized in order to have the best likelihood of success. Women with decreased ovarian reserve (DOR) can be especially difficult with respect to both quantity and quality of eggs.

Low Stim IVF, or minimal stimulation IVF, is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene citrate, Clomid and Letrozole) under the premise that it is a safer than conventional gonadotropin stimulation regimens and has comparable success. Many centers tend to use this approach as each cycle is less expensive than conventional stimulation regimens. The Low Stim IVF regimen is indeed safer, but by doing a lower dose stimulation, a smaller number of eggs are recruited and retrieved, which can therefore decrease the overall likelihood of success. While there might be some benefit to using this approach in particular subsets of women, it should not be universally applied.

Here at Sher Fertility Institute New York, we have successfully used minimal stimulation regimens with Letrozole in women with decreased ovarian reserve. Some women with decreased ovarian reserve, for an unknown reason, will have a slightly better response to low-dose stimulations than to a conventional stimulation protocol. That being said, an equal number of women will respond better to estrogen priming or flare regimens than to minimal stimulation regimens.

Some benefits of a low-dose stimulation with Clomid or Letrozole include the following:

  1. Milder stimulation may reduce the overall stress on the ovaries and will decrease the risk of ovarian hyperstimulation syndrome (OHSS).
  2. Women who otherwise do not respond to conventional stimulation regimens may respond and therefore have a chance of pregnancy, albeit lower (10-15% pregnancy rate) than that expected when obtaining a greater number of eggs/embryos.
  3. These regimens might be of benefit for those women who are concerned about side effects of higher dose stimulations.

Some drawbacks of undertaking a low-dose stimulation with Clomid or Letrozole include the following:

  1. While Clomid can assist in the development of multiple follicles, it has the undesirable side effect of thinning the endometrial (uterine) lining. This endometrial thinning causes the endometrium to be less optimal for implantation, so many centers using Clomid for minimal stimulation will recommend that all embryos be frozen while the endometrium recovers and the patient is scheduled for a frozen embryo transfer at a later date.
  2. On the surface, it would appear that using Clomid or Letrozole decreases the cost of an IVF cycle. However, given that the success rate is lower than with conventional IVF, the number of cycles/egg retrievals typically required for success increases. So, the actual cost of the entire treatment cycle (meaning 2-3 cycles of IVF) significantly increases. When this is taken into account, the cost associated with Low Stim IVF can be significantly higher than conventional IVF. In addition, there is the very real additional emotional cost associated with a much higher failure rate with Low Stim IVF.

So, minimal stimulation with either Clomid or Letrozole does have a place in the armamentarium of IVF stimulation protocols. In select patients, these regimens may in fact be successful. That being said, patients need to be aware that these methods oftentimes will require multiple stimulation cycles in order to obtain the same success as is seen with conventional methods. And with multiple cycles comes additional cost.