More and more women are deciding, based upon personal preference and professional necessity, to postpone having a family to a later age. In fact, very recently Janet Jackson (49Y) was in the news stating that she was cancelling her tour to prepare for treatment needed to have a baby. This event prompted me to write this article on IVF in women of a more advanced age The truth is that hardly a day goes by when I am not asked the question of, “How old is too old to do IVF?” The standard answer for women under 43Y, provided that they have an adequate number of eggs (ovarian reserve), IVF with own eggs is definitely an option. After 43y the percentage chance that an IVF cycle (where the woman uses her own eggs) will result in a live birth, declines to the single digit range and after age 45Y it falls to well under 5% per cycle, making the use of an egg donor, the only rational choice. Any decision of when/ whether a woman’s age should affect a medical decision on whether or not to proceed to IVF, should also take into consideration the following: 1) The increasing incidence of pregnancy complications with advancing age 2) The risk to the baby of poor intrauterine development and premature birth, both with their respective risks 3) Ethical factors, such as age and its effect on projected life span, as well as the physical, emotional and financial ability to provide for the needs of the child. BUT it is not as simple as that! I will never forget a couple that travelled from Munich, Germany to consult with me regarding IVF with Egg Donation about 20 years ago. The lady, who will here be referred to as (JS) was 53 years of age and her husband (PL) was 44. At that time, we had a general policy not treat women over 50 years of age. When I informed her of this, she became very agitated. She responded that she was in perfect health, while her husband suffered from moderately severe hypertension and type 2 diabetes. She asserted that had the ages been reversed, (i.e. if she were 44Y and he 53Y) we would never have rejected them. She went on to insist that the ruling amounted to sexual discrimination….and you know what? She was right! I suggested that the couple personally present their argument to our Ethics Advisory Board…which they did. The board authorized me to perform IVF with egg donation. I did so and subsequently transferred two embryos to PL’s uterus. She conceived and gave normal vaginal birth (at full term) to two healthy girls. I have since heard regularly from this couple, receiving family photographs, virtually every year, and the two girls are now both in college. Sadly, PL passed away about 3 years ago and JS very recently got remarried. The new family is thriving. Any woman, regardless of age, given access to “competent” eggs/embryos, whether own egg or donor-derived, who has a receptive uterus (her own, or that of a gestational carrier), is capable of achieving motherhood through IVF. This ability is of course predicated upon the patient having access to a full spectrum of options. Herewith, a few basic considerations:
- Access to at least one “competent” embryo. It is a fact that as women advance beyond their mid-thirties, both the number and chromosomal integrity of their eggs, will inevitably decline. At age 30Y about 1:2 are chromosomally numerically normal (euploid) and “competent”, upon fertilization to implant in the uterus and propagate healthy babies. By age 40Y about 1:6 eggs are euploid and by the 42nd year, only about 1:10 will be “competent”. By the time the woman reaches age 45, only about 1: 25 harvested eggs will be euploid
Simultaneously, as the woman reaches her 40’s, the number of eggs remaining in her ovaries, (her ovarian reserve) will start to decline. This diminishing ovarian reserve (DOR) will be reflected in her basal blood FSH level rising progressively, and her blood antimullerian hormone (AMH) level dropping. What this means is that the woman’s pregnancy potential drastically declines as she emerges from her 30’s into her 40’s. The combination of age-related egg “competency” and ovarian reserve is referred to as the “biological clock.” By the time the average woman reaches 43y, both of these component parts of the “biological clock” will usually have declined substantially, such that after 43 years of age, she would be best advised to preferentially choose egg donation. The transfer of a single advanced embryo (blastocyst) to the uterus of a 43 year old woman, will likely yield less than a 10% chance of a baby. Conversely, a similar looking blastocyst found through chromosomal testing or PGS (using next generation Gene sequencing or NGS) to be euploid and “competent” could allow the same woman a 40-50% chance of a live birth. It thus follows that for women with such declining fertility potential, NGS embryo testing with “banking” (stockpiling) of several embryos over multiple IVF cycles will at the time of transfer to the uterus, dramatically improve the odds of success.
- A receptive uterus: For an embryo to propagate a viable pregnancy the uterus needs to be anatomically normal, its endometrial lining needs to develop normally in response to estrogen, and any underlying immunologic implantation dysfunction must be identified and corrected. Conditions such as uterine fibroids and adenomyosis are more prevalent in older women. And post-menopausal women who are estrogen depleted will find their uteri shrinking and the endometrial lining becoming ever less responsive to estrogen. It is important in such cases to prescribe estrogen hormone replacement therapy for 2-3 months, prior to performing embryo transfer.
- A healthy parturient, who is capable of carrying a baby to term. The Hippocratic Oath demands that physicians knowingly never put patients in harms way. Since pregnancy is inevitably associated with increasing maternal risk as the woman ages, it is important prior to embarking on fertility treatment in such cases, to perform a thorough physical examination and a barrage of tests that include, (but are not limited to) EKG, chest x-ray, blood chemistry (BUN, electrolytes, creatinine, liver enzymes, lipid profile, glucose etc..), mammogram, and PAP smear.
- A medical and laboratory team with the necessary experience/expertise, and with ready access to the most advanced options such as:
- Egg Donation
- Gestational Surrogacy
- Donor sperm (if needed)
- Genetic embryo selection (using PGS)
- Gestational surrogacy.
When it comes to a “cut off” for IVF eligibility, age is an important consideration, and the risk/benefit of any particular course of treatment needs to be critically addressed with patients but there can, in my opinion, not be any hard and fast rule. In the final analysis, each case must be considered on its own merit. As physicians, we have the responsibility of providing patients with information needed to make a decision without imposing our will upon them.