US and International patent pending
Since we can control the duration of the follicular phase, we can control term maturation by extending the follicular phase for a few days in an attempt to improve oocyte quality. This can be done in a natural cycle, Clomid/letrozole cycle, or ovarian stimulation with gonadotropins. Controlled ovarian stimulation protocols used to achieve term maturation are collectively referred to as Term Stimulation™.
The main general principle of controlled term maturation: the desirable number of days for the follicular phase is decided ahead of time and the protocol is continuously adjusted to achieve that goal. Each case is unique and there is no one-fits-all recipe.
Achieving Term Maturation in Natural Cycle
In the natural cycle, the follicular phase must be of a sufficient length for four reasons:
- The oocyte must have an adequate time for maturation.
- Endometrium must be exposed to estradiol produced by the follicle long enough to thicken it for implantation.
- The dominant follicle must have enough cells to form a competent corpus luteum (yellow body), which will produce progesterone to prepare the endometrium for implantation.
- The dominant follicle must become large enough to rupture following gonadotropins surge
In the most fertile age, the optimal duration of the follicular phase is 16.5 days. According to the Term Stimulation™ theory, the duration of the follicular phase must be as close to 16.5 days as possible. Furthermore, the theory suggests that with advanced age, extending the follicular phase even further, to 17, 18 or even more days may be beneficial. This can often be accomplished using non-steroid anti-inflammatory medications and by lowering the FSH by estradiol preparations.
However, these follicular phase manipulations are not trivial and require a skillful physician with relevant experience, daily measurements of FSH and E2 in serum as well as several ultrasound monitorings.
One of the important tips for the natural cycle is using a fertility monitor, such as Mira Fertility (or any other) because you have to make sure that whatever you are doing to extend the cycle is actually working and you do not miss your LH surge and ovulation.
Term Maturation in IUI
Term Stimulation™ in IUI follows the same general idea as a term maturation in a natural cycle with one difference: the patient receives oral preparation of Clomid or letrozole to increase FSH availability. An important point to stress, even though it seems obvious, the monitoring of serum FSH during a Clomid/letrozole IUI cycle is very important. This is because it may need to be adjusted by lowering the dose of Clomid/letrozole or by administering estradiol if the follicle is growing too fast.
Term Maturation in the IVF Cycle
Term Stimulation™ in the IVF cycle usually requires resulting embryos to be frozen before the transfer, because it has the potential to be accompanied by vanishing follicles with a premature progesterone rise.
Term stimulation is continued until the desirable duration, (usually 16 days) is achieved. The days are counted from the first day of the period. For example, if the stimulation is started on day 3, triggering a patient on day 13 or 14 will result in the 16 or 17 days of term maturation.
During Term Stimulation™, the last few days follicles are protected with NSAIDs and Citrotide. Despite the protection, it is likely that some of the largest follicles will be lost. However, this is a necessary sacrifice to improve the quality of the remaining oocytes. It is also comforting to remember that the largest follicles do not contain the best quality oocytes. If the follicle that started to disintegrate prematurely does not vanish, a post-mature oocyte may be retrieved. This should not be a deterrent against Term Stimulation™.