Physician-To-Physician Consult

Dear Colleagues

I have a 27 y-o patient, unmarried, with breast cancer that approached us for oocyte cryopreservation before starting chemotherapy.
Ovarian stimulation was started few days ago with hMG (Menopur) and tamoxifen was add to the treatment.
We wish to give her GnRH agonist for the final stage of oocyte maturation, aspirate the oocyte for cryopreservation.
We wonder if pregnancy rate of vitrified thawed oocytes are different in patients who received hCG or GnRH agonist for the final stage of oocyte maturation.
Please be kind to circulate it among the expert in the field as we would be happy to maximize the patient's ability to further become pregnant.
Thank you and have my best regards.

Dr. Allis MacMillan, USA

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Answer by Ariel Weissman

There is certainly no problem with GnRH agonist trigger if oocytes/embryos are to be vitrified. This approach will certainly add considerably to the patient's safety as it will not only eliminate the risk for OHSS but also reduce the pain and discomfort associated with prolonged ovarian enlargement. Concerns about GnRH agonist trigger are only raised is a fresh transfer is planned.
Ariel Weissman, Israel

Answer by Diego Ezcurra

The answer is No, maturation rate is exactly the same if retrieval is being done at the right time.
Diego Ezcurra, DVM, MSc, USA

Answer by Norbert Gleicher

Sorry, but we have no data on this. My only comment relates to the fact that breast cancer patients often produce only relatively few oocytes. We, therefore, attempt IVM if we have have immature oocytes, and in such cases hCG vs GnRG-a, at least theoretically, could make a difference.
Norbert Gleicher, USA

Answer by Zsolt Peter Nagy

We dont have a meaningful number of patients in this situation to compare hCG vs. Lupron (agonist) trigger.
We have however, a large number of oocyte donors where we do have outcome data after hCG vs. Lupron (agonist) trigger, - and the results are the same (same survival, fertilization, embryo development, pregnancy rates). Therefore, if it is preferred to avoid hCG trigger, then Lupron trigger should be a good option.
Zsolt Peter Nagy, USA

Answer by Ana Cobo

We agree that women with breast cancer can produce a lower number of oocytes (Domingo et al Fertil Steril 2012). Due to our experience with oocytes donors, we can say that aGnRH triggering provides excellent outcomes. It is worth to mention that many of them are aimed to oocyte vitrification for our egg bank and outcomes as good or better that before. Patients with hCG triggering will achieve outcome neither better nor worse. In case of doubt, you can make double triggering, with hCG to be conventional, and add aGnRH to take advantage of the FSH rise which suggests a greater oocyte competence.
I am copying Juan Garcia Velasco who is really the expert on this field.
Ana Cobo, Spain

Answer by Adrian Ellenbogen

Actually if the concern of Dr. Allis MacMillan is the possibility of OHSS to develop due to stimulation of this patient, GnRHa should be the option. We do not have experience with vitrification of oocytes. However we do not observe detrimental effect of GnRH-a trigger on embryo quality in routine IVF treatments. We do have experience with IVM and in this case hCG administration should be the option Adrian Ellenbogen, Israel

Answer by Andreas Schmutzler

- We do not have uncontested, reliable published data in this case.
- We cannot speak about a standard in the sense of EBM.
- This is exactly why you asked!
- We have to decide on which side of the optimum we would prefer to be wrong.
- In this case here it is between the health of the patient concerning her cancer, and her fertility.
- Decisions must be made depending
-- On her: If in doubt I guess she might opt for her health.
-- Her physician: he would have to do the same.
-- On extrapolation of the present data.
1. Opinions / data concerning her health:
- It is not in our field of expertise.
- Our very competent oncologists here for years say stimulation does not matter.
- I think there are no specific data.
2. Opinions / data concerning her fertility:
- HCG is still the standard therapy.
- Agonists are not experimental any more and seem to be working as well as HCG.
- As mentioned by others HCG is safer concerning IVM.
3. Conclusion:
The risks of harm to her cancer disease seem to be low, so for safety reasons for her fertility I would opt for HCG.
Andreas Schmutzler, Germany

Answer by Dror Meirow

To our experience women with breast cancer produce the same response like healthy patients age adjusted. We use both long and antagonist protocols.
As for GnRH triggering here is my concern and question.
During the last month 3 different doctors from different centers came across a frustrating situation. Patients for FP underwent antagonist cycle with an excellent response- progressive follicle growth, high adequate E2 levels, timed triggering, timed egg collection. HOWEVER, NO EGGS ONE CASE, INAPROPRIATE 2 AND 3 EGGS IN THE OTHERS.
As these patients had only one chance these are devastating results.
Options that were raised to explain included :
1. Bad medication- 3 different centers, however in all cases LH levels were not available post triggering.

2. Administration of the Antagonist in the evening only few hours prior to GnRH. Does someone have experience with this?

3. Too high E2 levels that might interfere with LH secretion.

4. Time between triggering and egg collection – in all cases the time was no less than 36h.

I will be happy to receive your comments.
Meanwhile I feel safer with Ovitrelle or at least to measure LH post GnRH prior to egg collection.
Happy New Year and Happy Holidays
Dror Meirow, Israel

Answer by Norbert Gleicher

At our center for the longest time we had a conflict between David (Barad) and myself about use of antagonist cycles in women with poor ovarian reserve.
One day, not too long ago, David decided to look at the experience we have had since one of us used antagonists the other did not. What he found was that if a woman really has poor ovarian reserve antagonist often (not always) kill off eggs. We end up getting lower egg numbers and poorer egg quality.
Intuitively and anecdotally I have held this opinion since antagonists were introduced. Like everybody else I then switched our then very large 2000+ cycle program (in Chicago).
Within 3 months I switched back because we noticed 2 immediate changes: Our egg donor pregnancies dropped by ca. one-third, and our pregnancies in women with low ovarian reserve dropped even more.
Dror, I am, therefore, not surprised by your experience and would suggest that these patients are, likely, those with borderline poor ovarian reserve.
Remember egg quality is the first sign; egg numbers declining follows at a somewhat later stage!
Norbert Gleicher, USA

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