The question
Hello Dr Sher I have just completed my 2nd ivf which failed due to my 13 follicles in egg collection being empty. The consultant diagnosed me with genuine empty follicle syndrome.
I am 36 years old with a AMH of 15. I had a short protocol this time with ovaleap and fyremadel firstly. All my follicles were roughly between 19-22 mm before egg collection. They triggered me this time with 250 ovitrelle and 1ml of buserelin. I had a reaction to the buserelin as it brought my stomach instantly into a lump. I found it strange how my last scan I literally felt like I was going to pop , however the following morning after I double triggered the night before I woke up to no more pain or uncomfortable bloating. I contacted my nurse and she said it could be due to the follicles being told to stop growing so to speak. But I felt odd how the pain had gone completely.
My previous 1st cycle if ivf was a long protocol. Again they used Ovitrelle 250 and again could only get 1 egg out,the rest where again empty. This one egg resulted in my 21 month old daughter.
They took a blood test after the 1st egg collection and found the trigger shot had absorbed. But not at the normal rate.
This cycle they didn't take a blood test after and the consultant said that re-triggering after 36 hours would not work. In hindsight I wish I pushed this but due to the shock and groggyness of the drugs. I didn't push it. Do you think this may have worked?
Do you think I should change the trigger shot or dosage? I don't have pcos, endo or heavy periods. I have a regular 26-28 cycle. But I only have a 2-3 day cycle now. My husband is 38 and his results have always come back fine.
Any advice would be much appreciated, thank you,
Laura
Answer from Dr. Geoffrey Sher
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Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
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ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)....... for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
http://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
- “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
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General information only, not medical advice for your own situation. For that, book a consultation.