To find the best IVF protocol for you, we look to your personal medical history, we decide upon the medication dose, and then finally we individualize your care against one of several standardized protocols.
We need to know your ovarian reserve (FSH and antral follicle counts…for more, look here). For example, if you have a good ovarian reserve, you won’t need very much stimulating medication. Conversely, if you have few eggs, you might need a higher dose.
In addition to ovarian reserve, we also need to estimate your personal ovarian sensitivity to hormones. This part is more art than science. It is very helpful if you have used stimulating medications in the past (eg through insemination cycles) as a guide. We also use your age, your BMI, and knowledge of pelvic compromise (eg from surgery or endometriosis).
Through a combination of ovarian reserve and your ovarian sensitivity, we should have an idea of the ideal starting dose of stimulating medication. The dosing can be as little as 75IU, to a theoretical maximum of about 300-450IU. (You can probably take higher doses safely, but your kidneys will just excrete the excess). In Canada, the main two medications used are Gonal F and Puregon, though we will also use Menopur, Repronex, Bravelle, and Luveris, usually in supporting roles. Less commonly, some doctors will add clomiphene (Clomid, Serophene) or letrozole (Femara) into the mix.
natural start, long, OCP-antagonist, estrogen primed, and flare…
You can run a natural start cycle, which simply means that you come in at the beginning of your menstrual cycle, say on day 3, and if there are no cysts, you start the agreed-upon dose of stimulating medication. This simple approach is appealing because it is, well, simple. But there is a catch: it is quite likely that egg growth will be scattered across a variety of maturity levels. ”Scattered” maturation makes the ideal timing of egg retrieval difficult, and the cycle might suffer as a result.
More commonly, we like to suppress the ovaries before stimulation. The idea is that none of the eggs will develop too quickly…so that all the eggs will be ready at the same time. Suppression also allows us to schedule treatments. Too many retrievals on the same day would compromise pregnancy rates for everyone.
The longest, deepest suppression is done with the long protocol. It is, as the name suggests, the longest of the protocols: several weeks on the birth control pill in most cases, overlapping with a GnRH Agonist (Lupron, Suprefact, or Synarel) which is even more suppressive. By the time you are done with this pre-treatment, your ovaries should be well-and-truly suppressed. As you can imagine, there is the risk of going too far. When your ovaries are over-suppressed, the stimulating medications simply will not work. You will know this is happening to you when your estrogen starts off low –sometimes less than 50 pmol/l– and never climbs above 200 despite day after day of stimulation. This happens to my patients about 5% of the time.
So why use the long protocol? Because when the long protocol works, most clinics find that we get the best pregnancy rates.
Nonetheless, the long protocol isn’t for everyone. Particularly for women with a low BMI (less than 21) or other reasons to suspect sensitivity to suppression, we usually opt for an OCP-antagonist protocol. In this case, we use the birth control pill (aka oral contraceptive pill or OCP) for a bit of suppression, then once the cycle starts, use a GnRH Antagonist (like Orgalutran or Cetrotide) to prevent ovulation. I like OCP-antagonist cycles, and have had a lot of success with them recently. It is a more pleasant protocol for patients, with fewer injections and side effects. It is a bit more fiddly to run, however, and (in my opinion) greater attention to detail is required by the clinical team.
The challenge with using a birth control pill, for some women, is that even a low dose pill (Alesse, Yasmin) for a short period (2 weeks) is too suppressive. Natural start is one solution, but if the woman’s natural estrogen levels are not very high in the luteal phase, her FSH levels will drift up and…the ovaries will start to stimulate too early and egg growth scattering results. In these select cases, we can use estrogen-priming, in which an estrogen patch (0.1 q2d) or Estrace tablets (8mg daily) are used starting about day 21 in the cycle before stimulation. Estrogen priming is very successful in bringing down FSH levels, of real benefit to women of borderline ovarian reserve, and we have seen successful stimulations where none were possible before. The catch (there is always a catch) is that estrogen primed cycles take a long time before we can see if they are going to work…..when we have to cancel them, it is usually quite late into a stimulation.
Estrogen priming is usually matched with an antagonist to prevent ovulation. But there is one more protocol to consider: a flare cycle. A flare cycle may involve OCP or estrogen-only pretreatment, but the key is that a GnRH agonist (Lupron, Suprefact, or Synarel) will be started at exactly the same time as the stimulating medication. The result is invariably rapid egg development. A flare protocol is the most “raw” of the protocols, sometime yielding difficult-to-interpret results. But we do use it in select circumstances.
Tying it all together
There is no universal “best” protocol. However, there may be a best one for you. It is appropriate to discuss protocols and medication dosing with your doctor before your cycle starts, so that you feel comfortable that the path chosen should maximize your chances for a good cycle.
Low-dose stimulations are coming in vogue at present, and I can write to that topic if enough people are interested. But, in the main, we get the best ongoing pregnancy rates when we aim for a healthy number of mature eggs. For most cycles, that means 7-12 mature eggs at retrieval. I hope you find your cycle sets you up for success. Please let us know; happy stories are always a pleasure to read.