No such thing as empty follicles

Underdeveloped and mal-developed (dysmorphic) eggs often have an exceptionally dense surrounding cumulus cell cluster that tends to attach them tightly to the inner wall of the follicle. The hCG shot, which is intended to mature the egg and disperse(loosen) the cumulus cells so that the eggs will comes free upon suction and can thus be readily retrieved upon needle aspiration, often fails to cause sufficient dispersion of cumulus cells when the eggs are underdeveloped or dysmorphic. Consequently, such eggs are often so more tightly adherent to the inner follicle wall that they fail to release easily. In such cases the eggs may not be readily captured with the first attempt at follicle aspiration, requiring that such follicles be repeatedly irrigated (flushed) and or scraped to try and dislodge them. In severe cases, these fail to come free. When this happens there is a tendency to describe such follicles as being “empty” . Since this implies that such follicles did not house eggs, it is a complete misnomer. There is no such thing as “empty follicles”.

Since most RE’s can easily perform the technical aspects of ER and since better quality eggs tend to readily release with the initial attempt at aspirating the follicle it follows that failure to successfully aspirate an egg is often due to the egg being immature or dysmature. The latter is usually indicative of the egg having an abnormal numerical chromosomal make-up (aneuploid). “Poor embryo quality is virtually synonymous with embryo aneuploidy and in >90% of such cases this is due to egg (rather than sperm) aneuploidy.

Imperfection is part of the human condition. Thus a percentage of human eggs (regardless of age) will always develop abnormally (dysmorphism). Once exposed to an LH-surge or the “hCG-trigger” such eggs will have an abnormal number of chromosomes.

Egg dysmorphism and thus egg/embryo aneuploidy increases with age. In younger women ( <35yrs) 45%-50% of all eggs are aneuploidic, at 40yrs the incidence is about 60% at 43, approximately 80% and about 90% at age 45yrs. Fortunately, aneuploidic eggs/embryos fail to implant or miscarry early on in pregnancy. Sadly, depending upon which chromosome(s) is/are involved, developmental defects such as Down’s syndrome (Trisomy 21) sometimes occurs.

The unavoidable threshold risk of age-related egg dysmorphism and aneuploidy can however be seriously compounded through over-exposure of developing eggs to male hormones (predominantly-testosterone). These hormones are normally produced by the connective tissue (stroma) that surrounds the egg-bearing follicle(s). Overgrowth of the stroma occurs with advancing age (beyond 35years) and/or at any stage when ovarian reserve declines below a certain threshold (evidenced by poor response to fertility drugs, rising day 3 FSH level, falling Inhibin B levels, etc.). The eggs of such women are thus inordinately vulnerable to an over-exposure to LH-induced ovarian testosterone. In such cases, over-administration of LH-like products (hCG) or LH-containing fertility drugs (Repronex or the use of ovarian stimulation protocols such as “Flare-agonist protocols” that establish very high LH levels early on in the stimulation cycle) can be especially harmful.

There is little one can do to reduce the age-related risk of egg/embryo aneuploidy. However since the risk of compounding egg dysmorphism and thus egg/embryo aneuploidy can be avoided by individualized stimulation protocol selection and precise timing of the hCG “trigger shot”… both very important considerations when attempting to improve egg/embryo quality and IVF outcome, especially in older women and those with diminished ovarian reserve.

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