What matters most, the sperm or the egg?
Lately, there’s been a lot of news about the age of sperm and how it affects embryo development and pregnancy success. And that has also led to a lot of confusion. So let’s break it down!
The news is that aging sperm are found to have mitochondria that age too. This causes a malfunction in the sperm and leads to poor embryo quality. You can think of mitochondria as the battery pack that powers the sperm, giving them the energy to swim. So even though men make new sperm every 2-3 months throughout their lives, these sperm are of poorer quality in older fathers. We know that older fathers are associated with a higher risk of some chromosomal abnormalities and also with childhood cancers and autism. We don’t yet know everything about why this is the case. And this makes sense. If sperm only need to survive a few months, they don’t need long-lasting mitochondria.
The other issue with sperm aging is sperm DNA fragmentation. Older sperm have a breakdown in the DNA, which causes poor embryo development and miscarriages.
The egg, on the other hand, was found to have mitochondria that don’t age. Wow! Somehow, mitochondria in older eggs are the same as mitochondria in younger eggs. This also makes sense. Women are born with all the eggs they will ever have, about 1-2 million eggs. That means that a woman’s eggs were actually inside her mother’s body during gestation, and her mother’s health in pregnancy could affect these eggs. Crazy! So anyway, eggs need to survive a long time, possibly 40 or 50 years. But here’s where the confusion lies. Many people are using this new research to say that all the aging issues with reproduction are related to sperm, and not eggs. This is simply not true, and anyone who has tried to conceive a pregnancy in her 40s knows how challenging working with aging eggs can be.
The problem with ovarian aging is two-fold. First, we lose eggs that never get a chance to grow. By puberty, the ovarian reserve is down to about 400,000 eggs. From that point on, women lose about 1000 eggs per month. Most of these never develop and just die off due to programmed cell death. This is called apoptosis. However, every month, a few eggs, called a cohort, grow big enough to form a fluid-filled sac around them. These are called follicles, and your body can choose one of these to ovulate and usually wastes the rest. When we give fertility medications, we help the rest of the cohort to grow, rescuing some more of these eggs to use in fertility treatments like egg freezing and IVF. As women age, the cohort grows smaller as ovarian reserve shrinks, so we would get fewer eggs with IVF treatments. Once the ovarian reserve is really small, the ovary becomes resistant to the brain hormones that stimulate follicle growth. These hormones, LH and FSH, stimulate the growth of follicles and induce ovulation of eggs. Once women approach menopause, these hormones become elevated and remain high because the ovary is no longer able to make estrogen to shut these hormones down. By the time women reach menopause, periods stop, estrogen drops, and there are no more eggs. Finito.
The second issue is with egg quality. While it is true that mitochondria remain young and stable throughout the long life of an egg, other parts of the egg do not. One part of the egg that ages over time is called the spindle apparatus. See, eggs have two sets of chromosomes, and sperm only have one. Humans need two sets of chromosomes (46 total) to grow and develop normally. So, when the sperm fertilizes the egg, the egg must delete one of its sets of chromosomes. It does this by lining up all the chromosomes in pairs along a protein matrix called the spindle apparatus. It then “unzips” the chromosomes and moves one set outside of the egg in a little bleb called a polar body. As the egg ages, the spindle apparatus proteins start to degrade, and sometimes some of the chromosomes don’t get deleted, or too many are kicked out. Either way, you now have an embryo with an abnormal number of chromosomes, called aneuploidy. This is what causes Down syndrome, which is caused by an extra chromosome 21. Most aneuploidies don’t result in pregnancy, or else the pregnancy miscarries. By the time a woman is 40, nearly 80% of her fertilized eggs are aneuploid.
So the answer to the question is both. Both sperm and egg aging are important factors in fertility and successful pregnancy. Both are necessary to create a baby. The good news is that both sperm and eggs can be preserved and frozen safely for many years if you plan to delay fertility for any reason. You don’t have to rush to have children, and you can use these options to protect your fertility later in life.