This is the fifth in a series of responses to common questions about Failed IVF Treatment.

One of the biggest disappointments to patients undergoing IVF is to be informed after the egg retrieval, that there were far fewer eggs harvested than initially anticipated. In order to understand what causes this unfortunate situation and how to best prevent it from occuring, it is necessary to understand a few basic principles:

• The first concept that needs to be appreciated is that the egg retrieval procedure is relatively simple and technically very easy to perform in almost all cases.So, when fewer eggs are harvested than the number of follicles available, it is rarely due to a lack of technical expertise.
• The second important concept is that the egg plays a critical role in orchestrating follicular development. So it should come as no surprise that smaller follicles (less than 15 mm in mean diameter on the day of hCG trigger) are far more likely to contain grossly abnormal eggs and are thus also the ones that are less likely to yield the egg at the time of the egg retrieval.
• Third; all ovarian follicles contain eggs, so when at egg retrieval fewer eggs are harvested than the number of follicles present, it usually means that the eggs were not successfully retrieved from some of the follicles.

The egg release during normal ovulation: Normally, the egg is readily released within 38-42 hours of the initiation of the LH surge.For this to happen, the cumulus cells that surround the egg and bind it to the inner wall of the follicle must first disperse, allowing the egg to become loosely attached to the inner wall.Then, with the rupture of the follicle, the egg comes free and is ready to be transported to the fallopian tube for fertilization by an awaiting sperm.It is important to understand that the dispersion of the cumulus cells is orchestrated by signals emitted by the egg in response to the onset of the LH surge.An egg that is grossly chromosomally abnormal (complex aneuploid) is often incapable of signaling these cells to “loosen up” sufficiently, in preparation for ovulation.

The egg release during controlled ovarian stimulation (COS): the follicle/egg must first develop optimally under hormonal stimulation; at this point, the hCG trigger (analogous to the spontaneous LH surge) causes the egg to signal the surrounding cumulus cells to disperse.Thereupon, ovulation will occur about 38-42 hours after the LH surge has started, provided that the cells attaching the egg to the inner wall of the follicle have sufficiently “loosened”.

With in vitro fertilization, the egg retrieval is scheduled for 34-38 hours following the hCG trigger, prior to spontaneous ovulation. At this point (provided that the surrounding cells have dispersed sufficiently, allowing the egg to be suspended loosely from the wall of the follicle) the application of a suction force allows the egg to enter the needle and so be delivered to the collecting test tube and the laboratory.

However, in circumstances where the egg is severely aneuploid, it might not have the ability to respond to the hCG by signaling the surrounding cumulus cells to disperse sufficiently. In such cases, it might not be captured with standard needle aspiration.When this happens, the doctor usually resorts to flushing the follicle with media in the hope that this will detach the egg and allow it to be captured with subsequent aspiration.This sometimes works, but in other cases, the egg will fail to be released in spite of repeated flushings.In my experience, failure of the egg to release after one single flushing usually suggests that it is chromosomally abnormal.In such cases, even if further flushing causes it to be released, it will usually turn out to be “incompetent” (i.e., grossly chromosomally abnormal) and incapable of propagating a normal embryo upon fertilization.

The issue of harvesting too few eggs usually centers around poor egg quality (incompetence/aneuploidy) and those factors that promote this unfortunate situation.I have repeatedly pointed to the fact that advancing age (beyond 35 years) is associated with a progressive decline in egg competency due to a “wear and tear” effect over time. It should therefore come as no surprise that in older women there is an increased propensity for certain follicles to not yield eggs.

I’ve also alluded to the fact that the protocol of ovarian stimulation (which establishes the environment for egg development), as well as the timing of the hCG trigger, can influence the potential for egg incompetence (aneuploidy), and thus influence the likelihood that follicles will yield eggs at the time of attempted aspiration.Older women, as well as those who have diminished ovarian reserve, and those with polycystic ovarian syndrome (PCOS) are especially vulnerable in this regard.In such women, it is thus critical that an individualized approach to COS be taken to COS.It is also important and that protocols such as “micro-flare” that induce increased LH release and ovarian testosterone productionbe avoided, as should the administration of gonadotropins that contain large concentrations of LH (e.g., Menopur) in such women.

What about “Empty Follicle Syndrome?”With this situation, a woman who has developed follicles ends up with absolutely no eggs harvested, and this is glibly attributed to the fact that there were no eggs present in her follicles in the first place.In other words, her follicles were “empty.”Since all follicles have eggs, this is a contradiction in fact.Such cases are usually due to all the woman’s eggs having remained densely adhered to the inner follicle walls, due to them being severely abnormal and incapable of signaling surrounding cells to disperse.It should come as no surprise that many of these women are either older, have PCOS, or diminished ovarian reserve.The only remedy is to individualize the protocol of ovarian stimulation in a subsequent COS cycle so as to avoid overexposure of the developing follicles to an exaggerated LH induced ovarian testosterone response.This might not always be successful, but it certainly offers the best possible chance in a subsequent attempt at IVF.