Infertility is a very common problem affecting up to one in five couples – 186 million people worldwide – who are trying to become pregnant. A careful medical evaluation can usually determine the contributing issues in many cases – whether in a woman, a man, or both partners, and some might respond to treatment or need assisted reproductive tools like in vitro fertilization (IVF).
But in a substantial number of cases, no cause of infertility is found. Could inflammation be to blame for some of those cases, and if so, will an anti-inflammatory diet or lifestyle boost fertility?
Now, researchers at the Hebrew University of Jerusalem (HUJI) have suggested that chronic oral inflammation may impair female fertility by triggering a systemic immune response that affects the ovaries. This leads to oxidative damage, reduced egg quality, disrupted follicle development, and a lower live-birth rate. These findings point to a potential biological link between oral health and unexplained infertility, opening new directions for future treatments.
Prof. Michael Klutstein of HUJI’s Faculty of Dental Medicine, who heads the Chromatin and Aging Research Lab, worked with HUJI periodontology Prof. Asaf Wilensky and students Dr. Paz Kles and Stephen Ameho in uncovering a striking biological link between chronic oral inflammation and female fertility –suggesting that conditions in the mouth may have far-reaching effects on reproductive health.
“When couples can’t achieve a pregnancy, a third involves the woman, a third involves her partner, and the rest are “unexplained infertility, said Klutstein in an interview with The Jerusalem Post. “Our discovery could help find the reason for this third group. Similar effects might harm men’s fertility as well, but there’s a big difference; women have a limited number of ova, but men have huge numbers of sperm.”
It was published in the Journal of Dental Research under the title “Chronic Oral Inflammation Impairs Female Reproduction in a Murine Model.”
Despite the importance of this topic, not much is known about the mechanisms that govern the effect of chronic oral inflammation on female fertility, and specifically, on oocytes (immature female germ cell that develops into mature eggs, which is an ovum).
They decided to test the connection between implants and female fertility in terms of the outcome – the birth of healthy pups. To do so, they mated four females to males four weeks after implant insertion or used four age-matched but untreated females as controls. All females from the control group delivered litters within five weeks of mating. However, in the implanted group, only one of the four females delivered pups. Even that single birth was of only one live pup.
The researchers examined in a mouse model inflammation associated with dental implants – a common clinical scenario – and tracked how immune signals spread throughout the body. Their findings reveal that inflammation does not remain confined to the oral cavity but triggers a systemic immune response that reaches the ovaries.
Under full anesthesia and pain relief, all female mice underwent extraction of the upper left molars. Males did not undergo the procedures and were used only as mates. After four weeks of healing, two titanium implants were inserted in implanted animals but not in untreated controls, which were left with no implants. Four weeks after implant placement, the mice were euthanized, and tissues were collected.
Biological changes show reproductive outcomes
The results were significant. Chronic oral inflammation in the animals was linked to increased levels of inflammatory cytokines in the ovaries, along with shifts in immune cell populations. This was accompanied by oxidative damage to ovarian tissue, impaired development of follicles, and reduced quality of oocytes. These biological changes translated into measurable reproductive outcomes, with markedly reduced live birth rates observed under inflammatory conditions.
Asked what first made them suspect there might be a connection between oral inflammation and fertility, Klutstein said that “Amos and I have been studying chronic inflammation and fertility for a long time – 11 years. Endometriosis (in which tissue similar to the lining of the uterus grows outside of it, typically on pelvic organs) and lupus (in which the immune system mistakenly attacks healthy tissues and organs and can damage the skin, joints, kidneys, blood cells, brain, heart, and lungs) and other diseases involve chronic inflammation. The question was if the inflammation can move so far – from the mouth to the ovaries, and how this happens.”
He added he didn’t expect the evidence to be so strong. We were among the first in the world to investigate this.”
Studies now have to be conducted on humans, Klutstein explained, “but already, it would be a good idea for women who intend to undergo fertility treatments to go first to their dentist to see if they suffer from oral inflammation. Fertility specialists and dentists should cooperate more. We’re now looking for a drug that could be given to women before fertility treatment.”
The study also identified deeper cellular effects. Oocytes showed DNA damage and epigenetic changes like those seen in reproductive aging, pointing to a possible mechanism by which inflammation accelerates the decline in fertility. “Inflammation is often thought of as a localized response, but our findings show that it can have systemic consequences that extend as far as the reproductive system,” said Klutstein.
“This work suggests that chronic oral inflammation may be an underrecognized factor in female infertility, potentially contributing to cases that currently have no clear explanation,” he added. The findings add to growing evidence that oral health is closely linked to overall health. Chronic oral inflammatory conditions such as periodontitis are widespread and have already been associated with a range of systemic diseases, including heart disease, rheumatoid arthritis, type-2 diabetes, Alzheimer’s disease, chronic kidney disease, and inflammatory bowel disease.
The researchers note that further investigation in clinical settings will be vital for determining how these findings translate to patient care. If confirmed, the work could open new avenues for diagnosis and treatment, including the use of anti-inflammatory or antioxidant approaches to improve fertility outcomes. The study didn’t look into the possibility that the oral inflammation might cause miscarriage or pregnancy complications.
Another common oral inflammatory disease is peri-implantitis – an inflammatory condition affecting the soft and hard tissues surrounding dental implants. Driven by bacterial plaque, it causes gum inflammation, bleeding, and progressive deterioration of the jawbone supporting the implant. The US Centers for Disease Control and Prevention reported that in that country, 47.2% of adults aged 30 years and older have some form of periodontal disease, and 500,000 receive new implants each year.
If left untreated, it can lead to implant failure and tooth loss. site-specific, affecting both the soft tissues and bone around osseointegrated implants in which artificial teeth fuse with the jaw bone, creating a stable foundation for the new tooth. It usually takes three to six months, but it can vary based on health and bone quality. In the US alone, about three million adults currently have dental implants.