An ever increasing number of women are deferring having babies until they have fulfilled career aspirations. Advancing age is associated with a progressive increase in the number of chromosomally abnormal (aneuploid) eggs and consequently a decline in egg “competence” (i.e., the ability to propagate embryos that can produce babies). Since it is predominantly the egg (rather than the sperm) that determines embryo “competence” it follows that as women get older, they experience an inevitable decline in reproductive performance which manifests in reduced fertility, as well as increased miscarriages and birth defects such as Down’s syndrome. Both are attributable to egg aneuploidy. It is therefore not surprising that the mean age of women seeking IVF services is also on the rise. The woman’s age, largely through the effect it has on her eggs, determines both her natural fertility potential as well as her ability to achieve success following In Vitro Fertilization. But age can also impact on the woman’s ability to successfully complete a pregnancy as well as the health of the baby she gives birth to. Older women (reproductively speaking) – especially those over the age of 39 – are much more likely to have underlying medical conditions such as diabetes, hypertension, coronary and cerebral vascular disease as well as an increased potential to develop thromboembolism. For this reason it is advisable that such women routinely undergo detailed screening before embarking on a journey to achieve a pregnancy. A full physical examination as well as pap smears, pelvic ultrasound and tests such as EKG, chest X ray, blood urea/electrolytes/creatinine/lipid profile/thrombophilia panel/liver enzymes as well as a glucose tolerance test should be done. Women who pass such testing often are not that much more at risk at developing pregnancy-induced complications such as preeclampsia, placental abruption, gestational diabetes, and pre-term delivery than are their untested counterparts. Their babies are also far less likely to be low birth weight and/or to suffer maternal age-related complications such as autism and intrauterine growth retardation. It is unfortunate that older women only come to realize their predicament when they are already confronted with the ravages of the biological clock. At that point, most will be faced with only two options. The first is to attempt to have a baby using their own eggs; the second, to consider In Vitro Fertilization with eggs derived from young donors and which are less likely to be chromosomally abnormal. Consider the fact that at age 35, about 2 in 3 eggs are aneuploid, at 40 the chances are about 6 in 7, and at 45 years, more than 9 in 10 are “incompetent.” Obviously, most women would far prefer to have a baby using their own eggs than those of an egg donor. In fact, in my experience, most couples will push to at least have one attempt with their own eggs before going to IVF-egg donation — even those who also have severely diminished ovarian reserve and have little chance of achieving a pregnancy with their own eggs, whether or not IVF is used. They simply have a need to reach “closure” before moving on. Not only is this understandable, but it is their right to make such a decision, which their IVF doctor should not deny them simply on the grounds that it will lower his or her statistics. It should be the patient’s choice to make, provided that there is no medical reason to believe that either the IVF process or an ensuing pregnancy will place the patient in harm’s way. It is our responsibility as IVF physicians to disclose all information necessary to patients that will enable them to make informed choices, not to dictate those choices to them. Egg donation is the preferred treatment for all women with depleted ovarian reserve (regardless of their age) as well as for women over the age of 43 years (regardless of their ovarian reserve). The chance of a woman of 43 years or beyond having an IVF baby with her own eggs is well under 10% per attempt. Thus, any such woman desiring to use her own eggs should be informed of this fact. If, in spite of this information, she still chooses to proceed, and is physically and mentally healthy enough to do so, she should be afforded the opportunity to try. I will never forget a patient who came to me at the age of 47 years demanding to do IVF with her own eggs. In spite of my protestations, she ultimately prevailed and we embarked upon what I then considered to be an exercise in futility rather than fertility. It took several attempts but she did conceive and her healthy little boy that she delivered (my Godson) at age 48, currently bears my name. While this serves to remind us that no matter how clever we think we are…. “man proposes while G-d disposes” it should not and does not suggest a change in policy with regard to the age beyond which a woman should preferably choose to use an egg donor. I’m often told by older women that the reason they are reluctant to use an egg donor is that this would deny them the ability to have their own biological child. My routine answer in such cases is that the woman who gives birth is by definition the biological parent. No man can bear a child and thus he can only be a genetic contributor….never a biological parent under the former definition. Under normal circumstances the woman is both a genetic contributor and a biological parent. Thus, giving up the genetic component by using donated eggs still enables the woman to share her biological contribution with her partner as a genetic parent and together with him to create a nuclear family. There have been several important recent advances in the field of advanced assisted reproduction that provide attractive options to women who anticipate to, or find themselves already in a situation where they seek to have a child at a later age. These are the following:

1. Customizing ovarian stimulation: As women get older, so do their ovaries. In the process, they respond differently to standard, “recipe” protocols of ovarian stimulation. What works in the younger woman does not necessarily work in an older woman or in a woman with diminished ovarian reserve. In such cases, protocols of stimulation need to be customized to meet individual needs. To the developing follicle and egg in such women, the biggest enemy is overexposure to LH-induced testosterone, which compromises egg development and increases the risk of egg aneuploidy. In such women, it is important to avoid protocols that either deliver too much LH (fertility drugs such as Repronex and Menopur have too much LH-like activity) or that cause the release of too much LH (“flare” protocols or the administration of Clomiphene and/or Letrozole). Ideally, in such women who undergo ovarian stimulation, LH concentrations should be kept low prior to and during the stimulation. My preference is to prescribe what we call agonist/antagonist conversion protocol (A/ACP) with or without estrogen priming. Having said this, it is important to note that even the ideal protocol cannot counter the inevitable increase in egg aneuploidy that occurs with advancing age. All it can do is avoid compromising the ovarian environment during ovarian stimulation and further prejudice egg quality.
2. Blastocyst transfers: A blastocyst is an advanced embryo that contains more than 100 cells. It takes 5-6 days for healthy embryos to reach this stage. Those that do not make it are almost invariably aneuploid and not worthy of transfer. Those that do make it are more likely to be (but certainly not always) chromosomally normal. Thus, other than convenience, there is little reason to transfer earlier cleaved (day 2-3) embryos. Furthermore, by taking embryos to the blastocyst stage it is possible to improve the “efficiency” of the IVF process. With few exceptions, I recommend this to my patients.
3. Vitrification (ultra rapid egg/embryo freezing): Conventional (slow freezing) causes ice crystals to form in the cells and so damages them. That is why in the past, IVF success rates using frozen eggs or embryos have been much lower. With vitrification, the rate of freezing occurs 600 times faster, thus avoiding ice crystal formation. As a result, eggs and embryos so frozen are virtually as viable as are their fresh (unfrozen) counterparts. In addition, more than 95% of embryos and eggs will survive thawing following vitrification.
4. Embryo banking: Since older women often produce few eggs/embryos per cycle and a small percentage of these are likely to be “competent” there is often an advantage in performing several egg retrieval procedures sequentially (over several months) in order to stockpile as many embryos as possible. In this way, the woman can prolong her own reproductive potential by subsequently transferring 1 or more embryos to her uterus at a time.
5. Genetic embryo selection: We recently introduced Comparative Genomic Hybridization (CGH) as a method for identifying chromosomally normal eggs and embryos. This process now allows us to selectively transfer only embryos that are chromosomally normal or are derived from CGH normal eggs. When we transfer such embryos, the baby rate per embryo is dramatically improved, and when we vitrify eggs that are CGH normal, the baby rate per frozen egg is at least 7-fold greater than when non-genetically tested eggs are used. CGH may well turn out to be a “game changer” in IVF, but in the case of the older women considering embryo banking, it has a special significance. In such cases, it is possible to provide the older women with more confidence that her vitrified, CGH tested, banked embryos have a high potential to propagate viable babies regardless of her age.In cases of IVF with egg donation, CGH affords the opportunity to store only “competent” embryos and then to transfer only 1 or 2 at a time (at a later date). This avoids the risk of high order multiples (triplets or greater) and at the same time facilitates convenience in that the woman does not need to synchronize her cycle with that of her chosen donor.Another advantage of this method is that it allows younger women to bank their eggs for future dispensation. This is especially advantageous for young women embarking on a career and who know that by interrupting their career path through having a baby, they might fall behind in the opportunities otherwise available. In other words, women who intend to delay child bearing can stop the biological clock by selectively banking their genetically tested eggs. We call this Fertility Preservation (FP). It has been estimated that the demand for FP is probably 7 or 8 times larger than for IVF. Egg freezing also opens the door to donor egg banking. We hope soon so establish the world’s first genetically tested egg bank – wherein we will compile a large selection of CGH tested donor eggs. What this will do is allow women/couples to choose one or more eggs (based upon their need and preference) for thawing and transfer without having to embark in a detailed complex and tedious donor selection process. It will shorten the time involved in an ovum donor cycle, will improve success rates per embryo transferred (and thus reduce multiple birth rates) while drastically reducing the cost of service in the US.

Older women face two opposing situations. The first is that as they get closer to the menopause, diminishing ovarian reserve will inevitably lead to a reduction in the availability of their eggs. The second is that as they get older, the quality of their eggs will decline at an ever increasing rate. Thus, time becomes their enemy. On the other hand, once a decision is made to go to egg donation, the issues of both egg quality and ovarian reserve fall away. The only area of concern that remains is their ability to safely complete a pregnancy. It is this grappling with the decision as to whether they should use their own eggs or go to egg donation that often creates the greatest amount of torment. It is our responsibility to help them navigate this journey, and in doing so, it is often necessary to seek the assistance of qualified counselors, psychologists and sometimes even psychiatrists. As advising IVF physicians it is also important to avoid allowing personal preferences and prejudices to cloud our judgment. As physicians who have taken the Hippocratic Oath, it is our responsibility to try our best to “avoid doing harm”. Thus, it is essential to fully evaluate all patients we treat. When it comes to IVF where we actively induce a condition that if misdirected can indeed cause harm it becomes even more important to thoroughly evaluate our patients in advance of treatment. And in the case of older women who, when it comes to pregnancy, are even more vulnerable and at potential risk this becomes even more of an imperative.