Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hi Dr. Sher,
I’m writing you with a question regarding “empty follicle syndrome”. I recently completed an IVF cycle and had 22 mature follicles. My trigger shot was Lupron to help combat OHSS which I luckily didn’t get. I had blood work the day before retrieval and numbers looked normal. At egg retrieval the next day, they tried a few follicles but there was nothing. They gave me another lupron shot and we tried again the next morning and only got 1 immature egg. I am wanting to start round 2 of IVF but am very nervous about the same outcome. Is there anything you would suggest to a patient in a similar situation? Thanks for your help!
In myn opinion, this has to do with the fact that the eggs were not normal and as such unable to signal the cells binding them to the inner walls of the follicles to disperse and allow them to become detached and collected at aspiration. This could have to do with the protocol used for stimulation, timing of the trigger, the method used to trigger (i.e. the Lupron trigger) or some/all of these factors. Read the articles below and you will better understand my meaning.
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 who hyperstimulate (as often can occur with polycystic ovarian syndrome (PCOS), especially when an “agonist” (e.g. Lupron) “trigger is used or the dosage of hCG used is lowered to try and reduce the risk of OHSS developing. . In my opinion it is usually 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.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
•Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
•“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
•The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Dr. Sher,
I have a confirmed pregnancy after my second transfer. We are thrilled!
My question surrounds intimacy with my husband now with a confirmed pregnancy. Can you share your thoughts on this? Thank you.
Alex
Hi Alex,
CONGRATULATIONS!
I advise my patients to enjoy a healthy post-IVF intimate relationship. I tell them that short of vaginal sexual penetration, sexual encounters are encouraged. My advice to them is for safety sake, to avoid intercourse until ultrasound confirmation of a viable pregnancy. Thereupon…back to normal!
Geoff Sher
A very early hCG level @ 7dp5dt was just 5.
Two days later at 9dp5dt it was still very low at 14
I am assuming this is a chemical pregnancy however my Dr wants me to do a repeat beta 48h later on 11dp5dt
Even if the hCG is doubling, at such a low level I assume this cannot possibly be a viable pregnancy?
Kindest regards
Katy
I agree with your RE. Do not write this off until there is clear evidence of the hCG level not rising appropriately.
Geoff Sher
Dear Dr Sher, we have just had our second round of failed ICSI. My partner has male infertility factor but nothing so far has been picked up on my end. I am 31 years old
we had two good quality embryos put back (1 each time), grade 3B and 4B. Our clinic does not use ultrasound guided embryo transfer. On the first cycle access to my uterus was very difficult, with a second stage cannula used. The access was easier on the second cycle, but was very painful. The reasons the clinic is giving for failure both times is down to ‘bad luck’. I have asked them to test me for Immunological
dysfunction and thrombophilia, which they have agreed to do in the next few weeks. Other than this they do not carry out any additional testing, including any embryo testing. The only thing they are able to offer is to use a different culture media. We have two frozen embryos that we will use next cycle. Are there any other tests you recommend having at this stage that might provide us with some clarity as to why it is failing?
Hi Sarah,
Very respectfully, in my opinion, US guided ET is now a “standard of care”. Blind transfers just won’t cut it.
Geoff Sher
Doctor Sher I am having my first FET tomorrow (Monday) and yesterday (Saturday) I took some aspirin for a bad headache as I suffer migraines & lately aspirin has been quite effective vs codeine. I took 2 x 500mg aspirin soluble tablets. They are high strength aspirin. Could this affect my uterine lining negatively being so close to my transfer day? I’m nervous about it now, even though I know aspirin was used and is still used in low doses & you pioneered it’s use in Reproductive medicine some years ago. I have read you saying you no longer consider it beneficial, however do you now believe it could be counterproductive & actually thin the lining instead or just of no benefit either way?
The aspirin will thin the blood for 4-6 days after the last dosage. This increases the risk of unintended trauma of uterine lining during ET, resulting in “concealed bleeding”. This, should it occur can compromise implantation and is one of the reasons that I no longer advocate the use of aspirin. I am sure that your RE knows to be exceptionally delicate when it comes to introducing the ET catheter in order to try and prevent this from happening as far as is possible.
Good luck!
Geoff Sher