Consider the fact that between 40 and 43 of age, the success rate per cycle of treatment with injectible fertility drugs alone, with or without intrauterine insemination (IUI) is 2- 3%. Since it is 6-8 times higher with “conventional” With “conventional IVF” it follows that for such infertile for whom the biological clock is “ticking” IVF is the treatment of choice.
In most cases, an embryo’s “competence” (its potential to propagate a normal pregnancy) is determined by the chromosomal integrity (ploidy) of the egg, rather than the sperm that fertilizes it. Age progressively increases the incidence of abnormal numerical chromosomal egg integrity (aneuploidy) from about 50% in the early 30’s to >80% by the time the woman reaches her 40’s. To make matters worse, most women ages over 40 years of age develop diminishing ovarian reserve (DOR) as evidenced by rising basal FSH and declining blood AMH levels. This results from the decline in ovarian egg population, which once it drops below a certain threshold level and accompanied by an increased incidence in dysfunctional ovulation, a progressive resistance to fertility drugs, a lower yield of eggs/follicles in response to fertility drugs and growing vulnerability to “suboptimal” protocols for ovarian stimulation. Simply stated, unless the protocol used for ovarian stimulation is carefully individualized, women over 40Y and those who (regardless of age) have DOR, will be more likely to propagate chromosomally normal (euploid) eggs that upon fertilization are capable of implanting and propagating normal offspring. To add to the problem, there is nothing that can be done to mitigate this age-related decline.
Thus, the only way to increase the overall likelihood of successful IVF in older women is to:
- Individualize (“customize”) the ovarian stimulation protocol so as to meet individual needs avoiding a “same size fits all” approach,
- Improve availability of and access to of embryos available by cryobanking or stockpiling “competent” embryos, selected through preimplantation genetic screening (PGS), using reliable testing such as next generation gene sequencing (NGS), over several cycles and then selectively transferring one or two at a time to the uterus in later cycles (i.e. “staggered IVF”).
Unfortunately many infertile women in their 40’s, make the mistake of deliberately deferring the decision to do IVF until they have tried less expensive alternatives such as ovarian stimulation with or without IUI. In the process they often ignore the fact that the differential does not lie in the cost of a procedure. Rather it is lies in the cost of having a baby and it comes in the form of emotional as well as financial currency. The unfortunate reality is that once on the move the biological clock can unfortunately not be reset. Thus in my opinion infertile women of 40-43 years of age (and especially those who have never had a baby before) should consider doing IVF preferentially from the get-go.
For women over 43 years, where fewer than one in ten of their eggs are likely to be euploid, IVF with egg donation is in my opinion, the treatment of choice.