How repeated Controlled Ovarian Stimulation impacts the number of eggs obtained in your next cycle?

Yuliya Blazhko, MD.
Fertility specialist & obstetrician-gynecologist

IVF Abroad, Low Ovarian Reserve

How repeated stimulation (COS) influences the number of oocytes obtained in consecutive cycle?
From this video you will find out:
  • requirements for the donor’s Controlled Ovarian Stimulation
  • scheduling the cycle with donor eggs
  • normal responders and hyper responders to ovarian stimulations
  • inter-cycle (intraindividual) variability
  • correlation between the number of oocytes and live birth
  • repetitive oocyte donation at Gryshchenko IVF clinic


Controlled Ovarian Stimulation and the number of oocytes retrieved

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.

- Questions and Answers

I’m doing an egg donation with fresh eggs. My donor has donated 4 times, I will be her 5th. She had 3 confirmed pregnancies from 4 of her previous donations. Is this going to affect the quality of her eggs that it will be her 5th time?

As I have already mentioned, we don’t see any bad influence on all of the repetitive stimulation, and the fact that she confirmed pregnancies from 4 of your previous donations, it’s a good predictive factor that her oocytes have good quality, and that’s why it seems to me that it will not have a bad effect, and for the 5th time there will be the same good result.

In case, of using donors’ eggs in IVF, do you usually recommend having embryos PGD-tested or not? What is the regular procedure?

PGT- A is a procedure that is widely implemented in our clinic, and in spite of donors having a rather low risk of genetic abnormalities of embryos, there is still a risk. The risk is about approximately 30- 40%, but this technology led us to determine normal embryo structure and to avoid implementation failures or to minimize the risk of miscarriage.

Is this only relevant for donor eggs? Because I have low ovarian reserve & low AMH & previous ICSI has been with high dose stims, but I am thinking of doing milder stims & then batch cycling of 3x cycles to harvest as many eggs as I can, then do a frozen transfer. That is why I would hope we would have a possible sibling option also. This will be our 4th ICSI cycle, so I think we need to change a protocol as the previous one didn’t work.

No, this data is relevant not only for donor eggs, as I’ve mentioned, we decided to compare this result with patient simulations, but I have to say that AMH level and the ovarian result decreases with age. It’s not connected with repeated ovarian stimulation, the quality of the oocyte becomes lower every year. That is why if you provide several simulations from year to year, this is quite predictable that in 4 years, you will get fewer oocytes quantity then f.e. at first simulation.

From my own eggs, I used to get usually 5, and it created more or less 3 embryos. How many can I expect from a 28 y/o donor? How many eggs and how many embryos on average? My doctor said its usually 10-15 eggs and 2 good embryos. I find it hard to imagine because, with my 5 bad quality eggs, I used to get 3 embryos B quality, so I think it should be much more from a donor?

Actually, I agree with you that 2 good embryos from 10 or even 15 eggs are a very, very low number. Especially, in a donor who is 28 years old, her egg quality should be good enough, and her level has to be at least 50-60%, and out of 10 -15 eggs should give more than 2 good embryos.

I had 2 IVF attempts with my own eggs. One failed. Then I had a miscarriage. What would you recommend for me? Should I try with my own eggs again or with donor eggs? I’m 40.

I would advise you not to give up and to continue your journey to motherhood. I should say that you can try with your eggs as long as you can, but understanding that the chances of pregnancy reduce with age, and at the age of 40 years old, the chances are up to 10%. Using donor eggs your chances increase up to 60 or 70%. If you try with your own eggs, I will advise you to do genetic testing of embryos, but still, you have both options.

I will potentially be using a 22-year-old donor, she has a healthy child of her own. She has donated twice before, each time resulting in around 19-20 eggs, and 7 out of 10 embryos after PGD24 are euploid. Her last cycle was in January 2020. This time with us, it will be her third time. What sort of outcome we could expect with her? What sort of prenatal vitamins etc. would be important for her to take? How can we maximize a good outcome with good quality eggs and embryos?

Your outcome with your previous simulation was rather good, from 19 to 20 eggs and the euploid embryos rate was also very good and your age actually, it’s very perspective, that is why it seems to me that the 3rd time sure the outcome will be as good as it was already. About the vitamins, we advise to use folic acid in a dosage of zero and eight milligrams per day and nowadays we all have an insufficiency of vitamin D, that is why it will be useful to do an analysis for this vitamin in case she has insufficiency. What about maximizing the outcome, this might be a question to your doctors and your clinic, we guarantee to all the patients an indefinite number of oocytes and if we get fewer eggs from the donor, we can take the oocytes from our egg bank, and we can provide the necessary quantity of the oocytes to the patient.

Which day is the best day to do all the tests for donors like AMH, LH, scans, etc. day-3, do the results change between day- 1 to day- 5?

An AMH level does not depend on the day of the cycle, and the LH level is necessary to know of the day of egg retrieval initially, we just check the LH level day-3 or day-4, actually, every day between day -1 and day- 5 is a good day to determine this hormone.  About the scans we provide, and I would suggest doing a uterus and ovaries scan at the beginning of the cycle to have good visualization of antral follicles and to have an antral follicle count.

I’m 28, at 27 I froze my eggs for social reasons. I got 16 eggs but only 10 MII (metaphase II) eggs. Is this number low? Would you expect more mature eggs from those 16?

It seems to me that this number is quite normal, actually, we expect a good answer to controlling through a simulation when we get from 8 to 15 or 16 oocytes, that’s why 10 mature oocytes is a good result. I don’t think that after thawing, you will get more than 10 mature eggs because, at the moment of freezing, it was 10 mature eggs, but it still a good quantity.

Are the egg donors told by doctors to use folic acid and vitamins before they donate? Do you think as a recipient can request from the clinic to ask that anonymous lady for that?

We recommend our donors to take vitamins before they donate. If you can request it, I would say that depends on a clinic but actually, they can give you full information about the preparation of donors, and this is not a secret that’s why it seems to me that it won’t be any problem to ask the clinic what medications and what preparation they provide to the donor.

I am from Indonesia, egg donation is not legal here. Is it possible if I come to your clinic with my own donor and then come back to my country after the process, and how long does it take?

Yes, it is that possible and, it is called the individual donation program so you can provide your individual donor, we can do a stimulation for you and then fertilize donor eggs and to do an embryo transfer to your uterus. The process can take from 1 to 3 months, we need to get the oocytes, it will take about 2 weeks, and it all depends on your plan. We can freeze the eggs and do genetic testing and then put it through back to the uterus on your second cycle, or we can do it without genetic testing. On average, it takes about 1 up to 3 months.

Does your clinic offer guarantee Live Birth Packages?

We don’t really like those guarantee packages because these procedures are never 100% successful. That is why to guarantee something like this, is not very true, and usually, all those guarantee programs include several IVF attempts, and the price of this guarantee programs is sometimes 3 times higher than just the usual IVF program. That’s why at the moment, we don’t have such a program, but maybe in the future, we will
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Yuliya Blazhko, MD.

Yuliya Blazhko, MD.

Dr Yuliya Blazhko is a fertility specialist, obstetrician-gynaecologist and specialist in ultrasound diagnostics at Gryshchenko Clinic-IVF. In 2008, Dr Blazhko graduated from Kharkiv National Medical University and in 2008-2011 she completed an internship program specializing in obstetrics and gynaecology and simultaneously worked at the Surgical Department of GC-IVF. Dr Yuliya Blazhko is a member of ESHRE, the Ukrainian Association of Reproductive Medicine (UARM), and the Association of Obstetricians and Gynaecologists of Ukraine (AOGU). Since 2011 Dr Blazhko has been working at the Assisted Reproductive Technologies Department of GC-IVF.
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Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.