By Dr. M.I. Cassim
MBBCh (Wits) F.C.O.G (SA) • Mphil (Repro) Stellenbosch • Dip B.A. (Edinburgh) • MBA (Edinburgh)
Oocyte (egg) quality is an important determinant of fertility outcomes both for natural conception and in assisted reproduction. It is thus important to appreciate the factors which influence the quality of the oocyte. Until recently, it was assumed that all eggs were “created equal” that is …an egg is an egg. However, with the more recent advances in laboratory technologies, it is now apparent that there are significant differences between eggs within the ovaries of the same individual. These differences are influenced by a number of complex factors, which this article will hopefully try to elucidate.
To understand oocyte quality, one needs to appreciate the dynamics of egg production, storage, active removal or discard, recruitment for ovulation, dominance and release.
Further understanding of the genetic integrity and metabolic function is also critical to fertilizationand embryo development. When a female is developing in the uterus of her mother, her ovaries are actively populated with eggs and by the 3rdmonth of intra uterine life, the total egg population may reach 5 million. By the time she is born, this number has reduced to approximately 1 million, and by puberty, down to 300 000.
The important question is, why does this active removal of eggs take place from foetal and into puberty and beyond? If scientists more thoroughly understood this process, called apoptosis (programmed cell death), and the environmental, lifestyle and other factors that may influence oocyte reserves and the egg reserve pool, it will go a long way to advancing fertility treatment and lifestyle changes. It is currently theorised that the process of apoptosis is a form of egg ‘culling’, removing unwanted eggs from the system.
These unwanted eggs may be eggs that are deemed unnecessary for that particular individual or, more likely, unnecessary for the anticipated time period, environment, climate and other conditions which are likely to face this individual in the years to come. For example, there may be eggs with genetic memory for the ice age or pre historic conditions which no longer prevail. These eggs would be deemed unnecessary and are ‘culled’. It is possible that external stimuli and other factors input via the mother and extend the influence to the in-utero environment. Further direct external stimuli will continue to refine the process in early childhood and into puberty, hence the extension of the apoptosis/culling process.
What is definite is that the process of apoptosis is not a random phenomenon but a well programmed and co-ordinated process. However, if the external inputs governing the process are interfered with or disturbed, this may affect the oocyte pool and reserves and may thus influence future fertility. There is increasing evidence to suggest that egg morphology is getting progressively worse and that egg reserves are dwindling at a faster rate.
Another important aspect of egg quality is the process of recruitment and selection. Whilst it is accepted that the majority of women will release one egg per month at ovulation under natural conditions, it is not appreciated that to attain this single egg, a recruitment of nearly 50-70 eggs start about 4 months prior to release. The analogy is similar to advertising a job or employment position and short-listing candidates a few times until finally one is selected. The important difference however is that once a candidate is rejected they may never ever be used again and become atretic and thus non- functional.
Dysfunction of selection may also be influence by various factors and in the case of ART (Assisted Reproductive Technology), most commonly due to the use of ovarian stimulation drugs. This often forces unwanted follicles to develop and hence influences the embryo quality. A significant number of embryos in ART/IVF cycles have genetic aberrations called aneuploidy. Other factors that may disturb recruitment and selection may be related to polycystic ovaries, metabolic factors, thyroid disturbance, and other various factors influencing receptor function. Surgical damage to the ovary may also disturb the careful ‘flow’ of events within the ovarian micro structure. All these negative influences on recruitment and egg selection may occur despite a woman having regular periods and ovulating apparently normally.
This disturbance and disruption in the oocyte pool occurs ‘below the radar‘, and thus goes undetected even by routine blood testing. It is only with the recent advent of more sensitive tests such as Anti Mullerian Hormone (AMH) and the use of high quality ultrasound scanning that one can now be better able to assess ovarian reserves and what criteria may apply for removal of some eggs and preserving others.
AMH and AGE Relationship
The use of AMH assays as a predictive model of ART outcomes, as well as impending ovarian failure or menopause, is extremely valuable. Patients who would previously have been deemed suitable for IVF/ART based on the former more crude ovarian reserve tests would now be excluded as candidates for treatment. This would not only save patients tremendous financial costs but will also lessen the emotional burden of failed IVF cycles and unnecessary repeat treatments. Based on these ovarian reserve tests, some patients may be advised to opt for egg donation.
The AMH test, together with the pelvic ultrasound antral follicle scan has become an integral part of the workup of fertility couples embarking on ART or ovulation induction.
Finally, these tests may also influence important discussions on protocol selection and dosage for younger patients and those with PCOS (Polycystic Ovarian Syndrome) and may lessen the complication rate of OHSS (Ovarian hyper- stimulation syndrome), a potentially life threatening complication of ART.
In conclusion, not all eggs are created equal. Whilst the preservation of reproductive function is the basis of all living organisms, the situation in the human species is far more complex, just as the requirement for ‘survival‘ transcends beyond basic physical need. As a consequence of complex multivariate and diverse lifestyle, geographical, climatic and technological exposures (invisible microwaves etc), the human ovary is required to make equally diverse and difficult choices – which eggs to store and which to discard.
In most cases, it makes the correct choices, but there is growing evidence that the system is under increasing strain with obvious consequences for fertility and perhaps even our future survival as a species.
As a board member of the South African Society of Reproductive Science and Surgery (SASRSS), Dr Mohamed Iqbal Cassim, a fertility specialist, is one of a few doctors in South Africa qualified in both the laboratory aspect of fertility as well as the clinical aspect.
Dr Cassim together with Dr Dasoo currently run a hi-tech, world-class fertility centre in Brenthurst called BioART (Assisted Reproductive Technology).
After completing a MBBCH at the University of Witwatersrand in 1983, Dr Cassim began his career at the Baragwanath Hospital. He soon commenced with Specialist Training and became Senior House Officer in Obstetrics & Gynaecology. Thereafter, Dr Cassim went on to obtaining his registraship in Obstetrics & Gynaecology and became a founder member and chairperson of the Registrar Working Committee at the University of Witwatersrand.
He has also completed a short registrarship in urology which gives him greater exposure and understanding of the male factor in fertility problems. In 1992 Dr Cassim headed up a Gynaecology Unit at The Hillbrow Hospital and he was an examiner for undergraduates at the University of Witwatersrand Medical School.
Following an advanced training course in IVF at CICONIA Aarhus in Denmark, Dr Cassim went on to head up the Brenthurst Nordica Fertility Centre. He holds a Master of Philosophy (Mphll) in Assisted Reproduction at the University of Stellenbosch. He is currently completing an MBA with Edinbrough University.