IVF after 40 – The Fertility Fountain of Youth?

 

All too often popular culture makes IVF seem like the miracle cure-all for fertility problems, especially as women age. We are bombarded with images of glowing celebrities in their 40s, or even older, cradling their baby bump or with a “miracle” newborn in their arms. 

Any woman may choose to keep her struggle with infertility quiet, which is understandable since it is a very personal and emotional journey. But some women have admitted their use of fertility treatments, like IVF, to grow their family in their 40s. Brooke Shields, Celine Dion, and Beverly D’Angelo are just a few celebrities who spoke publicly, and there are many more every day women who have shared their journeys on social media. Unfortunately, despite the widespread successes of IVF for many women, its use does not guarantee a baby at any age.  

Women are born with all the eggs they will ever have – new eggs do not develop over time. What’s worse is that these eggs start aging even before a woman is born and simply continue to do so as time passes. The result is that both egg quality (eggs that are genetically normal) and quality (the actual number of eggs available for fertilization by sperm) diminish as a woman ages. This process does not necessarily occur on a predictable timeline and is different for every woman. As a result, if a woman aged 40 or older has not conceived after 6 months of unprotected sex, whether or not they are actively “trying” to conceive, it is time to seek an evaluation from a Reproductive Endocrinology and Infertility Specialist (REI) if having a baby is a priority and part of her life’s plan. Delaying evaluation may result in wasting precious time; a commodity that even IVF cannot always overcome. 

Some of the first tests an REI will perform are those looking at “ovarian reserve.” These tests include an  ultrasound and bloodwork, including AMH (anti-müllerian hormone) and FSH (follicle-stimulating hormone) levels. This helps estimate how many eggs are left in a woman’s ovarian reserve pool. However, ovarian reserve does not appear to be associated with other markers of a woman’s health.  Despite “40 being the new 30” in many aspects of a woman’s life (and health), ovarian reserve continues to decline with age regardless of how much healthier a woman may otherwise be in her 40s compared to her 20s or 30s. In other words, the physical health of a woman has no impact on the health of her eggs.

While ovarian reserve testing can be used to get a sense of a woman’s egg quantity, there is no testing available that can predict egg quality. This is largely because issues with quality do not become apparent until after fertilization. Once the sperm contributes its DNA to a fertilized egg, everything that activates cell metabolism and cell division to go from a fertilized egg to embryo relies on the components and genetics of the egg. It is in this very first cell division where we see most mistakes occur. Pieces of DNA that are necessary can be left behind or extra pieces of DNA may not be eliminated properly. These errors in cell division can lead to genetic imbalances in the embryo called aneuploidy (the condition of having an abnormal number of chromosomes). Aneuploidies are the most common cause of miscarriage at any age and are also associated with disorders such as Down Syndrome, where an extra amount of DNA from chromosome 21 is present. 

Preimplantation genetic testing (PGT) is available when undergoing IVF after age 40 to test the resultant embryos for aneuploidies. As a result, only genetically balanced, or euploid, embryos are transferred to the uterus, thus minimizing the chance of aneuploidy and resultant miscarriage. Approximately 80% of embryos in women over the age of 40 are found to be aneuploid, and this is reflective in IVF pregnancy success rates as well. Data from 2017 collected by The Society for Assisted Reproductive Technology (SART) show that per IVF cycle started in women aged 40 and older using their own eggs, only approximately 20% result in live birth. This chance decreasing as age increases, with only approximately a 3% chance of live birth in women older than 42 who use their own eggs during an IVF cycle. Studies show that the use of PGT to screen for aneuploidy increases the chance of success to over 45% in women aged 40-43 with a euploid embryo to transfer, which is near the 48% chance of success quoted by SART in 2017 for all women attempting conception using eggs from an egg donor. 

Technology is rapidly advancing, particularly in the field of reproductive medicine. Unfortunately, while IVF and PGT are amazing advancements in fertility treatments, they are not a guarantee, especially in women over the age of 40. Time is the most precious commodity a woman desiring fertility possesses.  Delay in seeking answers or treatment will not stop the biologic clock. The most important thing for a woman who is delaying childbearing for any reason until after age 35 or 40 to know is that she should not rely on IVF as a “Plan B” if she cannot get pregnant naturally. IVF is not always successful, especially in this age group. Any woman with questions or concerns about her fertility and delaying childbearing should consider reaching out to a REI to have these questions and concerns addressed.

 

References:

Decker M.  30 Celebrity Moms Who Had Kids After 40. Harper’s Bazar. Mar 2019.https://www.harpersbazaar.com/celebrity/latest/g18196402/celebrities-children-after-40-infertility/

Society for Assisted Reproductive Technology National Summary Report 2017. https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2017

Rubio C, Bellver J, Rodrigoa L, Castill_on G, Guill_en A, Vidal C, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized controlled study. Fertil Steril 2017; 107:1122–9.

Scott RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy in CCS and fresh ET significantly increases IVF implantation and delivery rates; an RCT. Fertil Steril 2013;100:687–703.

Lee HL, McCulloh DH Hodes-Wertz B, Adler A, McCaffrey C, Grifo JA.  In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43.  J Assist Reprod Genet (2015) 32: 435.