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Why Does Fertility Diminish With Age?

July 2, 2021
Cierra Lutz

Though the fact that fertility decreases by the age of 35 is widely known, much of the knowledge surrounding why is shrouded in mystery. We know a decrease in ovarian reserves is partially to blame - female babies enter the world with a limited number of oocytes, the cells from which mature eggs develop. We also know that the quality of human eggs declines over time.

A new study, published in the journal Aging Cell, cites another reason for decreased fertility: impaired RNA levels.

The cell’s ability to process gene products, known as the final maturation stage, provides the embryo with all of the materials needed to develop normally and survive. Typically, RNA molecules work at this stage to alter the function of genes that are involved in specific biological pathways. Age may influence this vital stage of development by directly impairing the levels of RNA molecules.

Man and woman's feet with a pair of baby booties.
It’s thought that a combined number of factors, both known and unknown, contribute to decreased fertility with age.

A Joint Effort

The Study

The joint investigation included researchers from the Centre for Genomic Regulation (CRG), the Centro Nacional de Análisis Genómico (CNAG-CRG) and the Clínica Eugin. The group sequenced 72 oocytes yielded from 37 donors, whose ages ranged from 18 to 43 years old.

They discovered the number of gene transcriptions responsible for chromosome separation increased with age, as did the amount of RNA processing. Researchers also found that as age increased, the number of gene transcriptions related to mitochondrial metabolism decreased. These findings, however, only occurred during the final stage of development.

Bernhard Payer, co-author of the study, stated that “...the final step of oocyte maturation itself might be negatively affected by age, which is critical for reproduction.” He continued, “what we don't know yet, is which of these changes are merely a consequence of the aging process and which may directly contribute to the quality drop in oocytes with age."

Further Results

The study also compiled the height and weight of each donor, in an attempt to decide whether body mass index (BMI) impacts an egg’s transcriptome. While age mostly affected the egg’s transcriptome in older women, BMI seemed to impact the transcriptome of younger eggs. This means that fertility decline due to age may have different mechanisms than those of an abnormal BMI.

The Study’s Conclusions

Though the researchers concluded more studies are necessary, it is believed that impaired RNA levels affect fertility. Payer and his colleagues believe their research may lead to advances in reproductive medicine, as well as potential drug treatments to repair aged oocytes.


In-vitro fertilization technique
The oocytes were fertilized via IVF before reading each egg’s transcriptome.

What is Fertility?

The Ability to Conceive

Fertility is someone with a uterus and ovaries’ ability to conceive a biological child. Typically, a person’s fertility may be questioned if they struggle to get pregnant within a year while having frequent, unprotected intercourse.

Microscopic view of IVF.
Past findings support the idea that being overweight or underweight may be associated with less-fertile oocytes and poorer reproductive outcomes.

What Else Impacts Fertility?

Lifestyle Choices

Though many women suffer from reproductive health issues that contribute to fertility problems, steps to promote a healthy lifestyle can be enacted to promote fertility at any age.

  • Maintain a healthy weight, to encourage regular ovulation.
  • Prevent sexually transmitted infections, such as chlamydia and gonorrhea - these are the leading causes of infertility in women.
  • If possible, avoid working the night shift on a regular basis: an inconsistent sleep schedule may affect fertility by inhibiting hormone production.
  • Don’t smoke. Smoking ages your ovaries and allows your eggs to age prematurely.
  • Limit alcohol consumption, as heavy drinking is associated with a greater risk of ovulation disorders. Quitting altogether during pregnancy is recommended, as experts have yet to establish a safe level of consumption, and drinking during pregnancy is linked with fetal alcohol syndrome.
  • Consider limiting your caffeine intake - fertility doesn’t seem to be affected by around 200 milligrams of caffeine per day.
  • Don’t over-exercise: too much physical activity can inhibit ovulation, as well as reduce production of the hormone progesterone.
  • Avoid harmful toxins, such as pesticides, laundry solvents, and lead. Exposure to toxins adversely affects fertility.

Reproductive Issues

Problems within a woman’s reproductive organs also impact fertility. If unable to conceive within a year having frequent, unprotected intercourse, consider seeing a doctor. They may check for:

  • Ovulation disorders, which impact the release of eggs from the ovaries. These include hormone disorders such as polycystic ovary syndrome and thyroid problems.
  • Abnormalities within the uterus or cervix, including polyps, can make it more difficult to get pregnant.
  • Damage or blockage of the fallopian tubes can also cause fertility problems.
  • A condition known as early menopause, diagnosed when the ovaries stop working and menstruation ends before the age of 40.
  • Medical conditions that inhibit menstruation, including diabetes, celiac disease, and some autoimmune diseases.

When diagnosed with a reproductive disorder, many people experience overwhelming fear and anxiety about the future. However, rest assured there are plenty of ways to form a family. And with these studies, which illuminate the various questions behind reproductive science, further advancements in fertility technology are closer than ever.



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