Dr Yuliya Blazhko, fertility specialist & obstetrician-gynaecologist at Gryshchenko Clinic-IVF, is discussing how repeated Controlled Ovarian Stimulation can influence the number of oocytes obtained in a consecutive cycle.
The donor’s controlled ovarian stimulation will be effective as long as there is a good number of oocytes of good quality. It has to be safe, any complications during controlled ovarian stimulation must be avoided. According to these criteria, patients with normal or hyper response to controlled ovarian stimulation need to meet the same requirements as the oocyte donors. There are several ways to start the cycle with the donor’s oocyte, we use fresh donor oocytes, fertilize them with their partner’s or donor’s sperm and then do the embryo transfer. In this case, synchronization of the donor and patient is required, and this is not always convenient because we can lose oocyte quality.
The second option is to vitrify the donor’s oocytes and then, do an artificial or natural cycle. The third option is retrieving fresh donor’s eggs, fertilizing and then further transferring them in the artificial or natural cycle of the recipient. Vitrification makes the protocol more convenient and flexible for patients and it also gives the possibility to genetically screen the embryos.
Synchronizing the cycles – donor’s and recipient’s
There are, again, several ways to synchronize the cycles of the donor and recipient. We can use oral contraceptive pills, long protocol with GnRH agonist, GnRH antagonist, estradiol (E2) and progesterone. Some data from meta-analysis shows that using contraceptive pills can influence the outcome of the IVF procedures, such as pregnancy outcome, and the probability of an ongoing pregnancy can be significantly lower in a patient who received contraceptive pills treatment. A definite reason is still unclear, theoretically, it can be because of the negative impact on the endometrial receptivity, in case we use vitrification of oocytes or embryos this is not so significant, and we can use this tool for synchronization.
In the case of using GnRH antagonist, the stimulation takes a bit longer and is somewhat more expensive, but it does not influence the outcome. Using estradiol is also a very convenient tool because we start administering estradiol before the start of the cycle and release a scheme in which we can regulate the day of oocyte retrieval depending on the number of days that estradiol is administered. This is very convenient, both for patients and the Alpha organization, and it’s always easier to plan and optimize the IVF cycle and procedures. Some data shows that using estradiol for pretreatment led us to get a bigger number of major follicles and a bigger number of available embryos, but it does not influence the outcome just like a clinical pregnancy rate. It is possible that getting major follicles happens because of suppression of FSH and coordination of follicles and follicle pool alignment. Therefore, this is quite a good tool for scheduling.
Types of stimulation protocols
There are a lot of stimulation protocols, there are about 19 types of them. The most commonly used are the long protocols and antagonist protocols. There is convincing data that shows that using GnRH agonist with HCG or GnRH antagonist protocol with an HCG triggering, there can be some complications such as hyperstimulation syndrome (OOHS). However, in case we use GnRH antagonist protocol with GnRH agonist triggering, there won’t be any complications after the stimulation. Therefore, this data helped to change the strategy of the stimulation of donors, and since 2012, the use of the long protocol was reduced and since 2015, this protocol is not used anymore. This helped to avoid OHHS. There is in fact a cut-off level of AMH, and it is 3. 36 ng/ml, as this is a risk factor for OHHS. Most of the time, oocyte donors have this or a higher level of AMH. Patients with such high levels are considered to be hyper-responders, therefore stimulation needs to be optimized to avoid any complications.