Can periodontal disease affect conception? A literature review.

Periodontal disease can be considered as a chronic inflammatory condition that includes gingivitis, a mild and reversible form that affects the soft tissues around the dental elements, and periodontitis, a severe form that culminates in the destruction of soft tissues, alveolar bone and other dental support structures ( Kavoussi et al . 2009 ). Specific anaerobic bacteria present inside the periodontal pockets are believed to be the main cause for the development of the more severe form of periodontal disease ( Hart 2012 , Hart et al. 2012 , Akcali et al . 2014 , Khanna et al . 2017 , Martelli et al . 2017 , Khalife et al . 2019 ). The activation of the host response, triggered by these microorganisms and their metabolites, stimulates the synthesis and release of cytokines, mediators of inflammation and metalloproteinases which then contribute to tissue destruction. The progression and severity of the disease will depend on the balance between the aggressiveness of subgingival biofilm and the individual immune response, with possible influences from the genetic and epigenetic context, and from some environmental factors such as sex, age, smoking habit and the degree of oral hygiene ( Martelli et al . 2017 ). Once the infection is established, a specific cascade of destructive tissue mechanisms is activated and triggered by the inflammation mediators. It is also possible that these molecules, as well as the pathogens involved in the development of the disease, do not remain confined to the periodontal tissue but reach the bloodstream and disseminate the infection ( Hart et al. 2012 , Martelli et al . 2017 ). During the 19th century and the beginning of the 20th century, there was the spread of the ‘focal theory’, which states that the presence of outbreaks of infections could influence the onset or progression of a wide variety of inflammatory disorders such as arthritis or heart problems. In this regard, more than 200 microbial species have been identified in apical periodontitis and more than 500 in its marginal variant. Since bacteremia in humans can reach very high levels (more than 1011 microorganisms per mg of dental plaque) and considering that these pathogens are close to the circulatory system, it is easy to understand how the systemic spread of bacterial products, as well as derivatives of the inflammatory response, is facilitated by these conditions ( Khanna et al . 2017 ). In support of these considerations, some studies have also suggested an alteration of inflammatory markers after a successful periodontal treatment, with a reduction in the levels of c-reactive protein and interleukins, and with an improvement in vascular and endothelial functions ( Hart et al. 2012 ). Furthermore, other studies have found high levels of IgG antibacterial serum antibodies in patients who have a chronic or aggressive form of periodontitis, compared to those present in individuals with good oral health and without early signs of periodontal disease. However, the presence of serum antibodies against periodontal pathogens does not confer immunity toward them and does not prevent the development of the disease, but is considered an auxiliary practice for its diagnosis ( Akcali et al . 2014 ). Due to the possibility of systemic dissemination of periodontal infection through the bloodstream, clear evidence indicates the presence of a correlation between oral and systemic health. Much of the literature recognizes that periodontal disease may represent a risk factor for numerous systemic conditions (including female infertility). In the last 20 years, there has been a constant development of the so-called ‘periodontal medicine’, which today is considered a very important branch of periodontal clinical research. For this reason, the maintenance of a good level of oral health is always encouraged in order to prevent or mitigate the course of a variety of conditions ( Martelli et al . 2017 ).

F S L was involved with the conceptualization, design, definition of intellectual content, manuscript review; A G S was involved in manuscript preparation, manuscript editing; E A G was involeved in manuscript review; A A was invloved in manuscript preparation, E S and SM were involved inmanuscript review.

After a careful selection, we considered 19 articles. Among them, 7 were observational studies, 4 literature reviews, 3 surveys, 2 case–control study, 1 letter to the editor, 1 pilot study and 1 case report. Table 1 summarizes the main characteristics of the included studies. Table 1 Literature articles included in the present review, with their main features and purposes, ordered by date. Reference Country Aims/purpose Methodology Key findings and results Shahryar et al . (2009) USA To verify the existence of a correlation or reciprocal influence between endometriosis and periodontitis Survey The study concludes that a correlation between these two conditions may exist due to the lack of immune regulation (e.g. caused by infectious agent) Klinger et al . (2011) Israel To examine the association between fertility parameters and the periodontal status of men attending fertility and in vitro fertilization clinic Observational study Possible association between periodontal disease, low semen quality and male infertility Hart et al . (2012) Australia To verify the influence of periodontitis on the time of female conception Observational study Periodontal disease may represent a risk factor for the increase in conception time, especially in non-caucasian women (+2 months)Need for further investigations McKinnon et al . (2013) Canada Presentation of a case report about pelvic inflammation due to Fusobacterium nucleatum Case report Translocation and diffusion of Fusobacterium n ucleatum through the blood route could lead to the establishment of reproductive health problems in the long term Nwhator et al . (2013) Nigeria To verify the level of knowledge about the correlation between periodontal and reproductive health among Nigerian doctors Survey Lack of knowledge about the correlation between oral and reproductive health Nwhator et al . (2014) Nigeria To investigate the relationship between periodontitis and male infertility Observational study A link between poor oral hygiene and low sperm count have been found Akcali et al . (2014) Turkey To investigate the level of periodontal pathogens in saliva and of antibody response in serum in subjects with polycystic ovary syndrome Observational study Polycystic ovary syndrome may affect the oral microbiota composition and the antibody response to certain members of the microbial community Umeizudike et al. (2016) Nigeria To assess Nigerian doctors knowledge regarding the possible correlation between periodontal disease and systemic health Survey Lack of knowledge about the theme in study and need for post-diploma training courses Paztor et al . (2016) Hungary To evaluate the correlation between poor sperm analysis results of male with idiopathic infertility and periodontitis Observational study Pathospermia and poor semen quality seem to be not associated with periodontal infection in men with idiopathic infertility Prager et al . (2017) Hungary To study the association between sperm pathology in idiopathic male infertility and periodontal/ dental status Observational study Poor periodontal status was associated with oligo and asthenozoospermia Khalife et al . (2019) Lebanon To study the correlation between periodontal disease and poor in vitro fertilization treatment results Pilot study No correlation was found between poor oral hygiene and outcomes of fertilization tratmentsNevertheless, periodontal health is an important factor for general health Chidambar et al . (2019) India To investigate the relationship between fertility parameters and periodontal status of male patients Observational study A relationship between male infertility, decreased semen quality and periodontal disease seems to have been found Tao et al . (2020) China To compare the prevalence of periodontal disease between subjects with semen abnormalities and subjects with normozoospermia Case–control study Periodontal disease in correlated with semen abnormalities and sperm motility Machado et al . (2020 a ) Portugal To compare the periodontal status among females referred to a fertility clinic with the one of a regional epidemiological sample Case–control study Females with searching for fertility treatments presented worse periodontal conditions Literature articles included in the present review, with their main features and purposes, ordered by date. Female and male with periodontitis and infertility. Literature was analyzed searching for a possible connection between infertility and the presence of periodontits. This literature review was performed formulating the following research question: What literature exists to explain a possible connection between periodontitis and infertility? A comprehensive literature search was completed for the keywords periodontal, disease, infertility, periodontitis, female, male using the Boolean operators ‘and’ and ‘or’ to identify combinations of these words, and limiting the search to the English language and to articles published in the last 10 years with at least two authors. Searches were completed in Medline and Scopus databases. The authors performed independent title and abstract review to include or eliminate potentially eligible articles. Then, independent full article reviews were performed on the articles included from the initial search to evaluate their relevance to the research question. After exclusion for duplicates and title, the abstract review allowed considering 23 items, and the full-text reading reduced the number to 19 articles.

In conclusion, the analysis of the cited articles shows that the information obtained is considerable, but not yet sufficient to establish with certainty the presence of a link between periodontitis and female/male infertility. Therefore, what emerges from the following review is the need for many other studies in order to obtain more data, even if there is no doubt that oral health does influence the quality of life of an individual, and that it is no longer considered separately, but an integral part of it. A constant maintenance of a good degree of oral health is definitely necessary. The updating and the presence of collaboration between the various professionals involved (gynecologists, obstetricians, dentists, etc.) are important. Dentists could advise on the correct hygienic maintenance, both professional and at home, not only to the pregnant women, but also to those who are planning a pregnancy in order to avoid the occurrence of unfavorable conditions.

Periodontal disease or periodontitis can be defined as a chronic degenerative disease with a bacterial etiology that leads to a gradual loss of the support structure of the tooth, such as the gengiva, periodontal ligament, cementum and alveolar bone. To date, this disease represents the main cause of the loss of dental elements in the world ( Singh et al . 2019 ). Severe forms of periodontitis affect a limited population in industrialized countries, about 10–15%, but its incidence increases with age. The peak is around 50–60 years of age ( Papapanout & Lindhe 2016 ). In recent years, it has been assessed that periodontitis derives from the complex interactions between the host defense mechanisms and the bacterial compounds contained in the biofilm. The bacterial plaque acts damagingly on two fronts: on one hand, there are damages caused by the direct action of the bacteria and their leukotoxins and enzymes which destroy the defense cells and the connective tissue. On the other hand, there is the inflammatory response triggered by the host and caused by the persistence of the plaque, which leads to the gradual destruction of involved tissues ( Cortesi 2017 ). However, its progression and severity can also be influenced by other factors: genetic predisposition, lifestyles, general health status (uncompensated diabetes), obesity, malnutrition, osteoporosis and osteopenia, psychosocial stress, hormonal changes, drug assumption, hematological or genetic disorders and other syndromes associated with the category ‘periodontitis as a manifestation of systemic diseases’ ( Lalla & Papapanou 2017 ). The International Committee for Monitoring Assisted Reproductive Technology and the World Health Organization (WHO) define infertility as a disorder of the reproductive system characterized by the inability to establish a natural pregnancy following regular unprotected or targeted relationships after a period of 12 months or more. This condition affects 10–15% of women while in the remaining 80–85%, natural conception occurs within the year. It is strongly influenced by age and lifestyle and it is most frequently found around 30–40 years of age and in particular in women. Moreover, Infertility is often associated with dysfunctions of the ovulatory process, disorders of cervical mucus production, endometriosis, adhesions present at the level of the endometrium, and the presence of particular anatomical conditions affecting the fallopian tubes or the uterus itself ( Khanna et al . 2017 ). This disorder is also frequently related to a high risk of adverse pregnancy outcomes, for example premature birth, low birth weight of the newborn and episodes of pre-eclampsia ( Martelli et al . 2017 ). Oral biofilm may be responsible for a ‘systemic impairment’ of an individual's health, due to the high inflammatory markers found in patients affected by periodontal disease. This correlation is given by the fact that the bacteria that underlie periodontitis and the mediators of inflammation do not remain confined only to the periodontal tissue, but can enter the bloodstream and spread, thus disseminating the infection and having a systemic effect ( Miragliotta & Mosca 2017 ). Supporting this hypothesis, the placenta and amniotic fluid may represent a real target for all those bacterial species and for their toxins which, in case of untreated periodontitis, could spread through the bloodstream and therefore become a cause of poly-abortion, preterm births, low birth weight, even going so far as to invalidate attempts at assisted reproduction with a consequent significant economic and biological cost. There are two mechanisms that would seem to be involved in this scenario: the first one is the dissemination of bacteria from the oral cavity through the bloodstream ( Khanna et al . 2017 , Martelli et al . 2017 ); to support this hypothesis, specimens of Porphyromonas gingivalis and Fusobacterium nucleatum found in some samples of amniotic fluid or placenta taken from mothers who had a premature birth and who were affected at the same time by periodontitis, and specimens of P. gingivalis and Aggregatibacter actinomycetemcomitans detected into the liquid amniotic of pregnant women affected by periodontal disease ( Martelli et al . 2017 ). The second one is the production of cytokines and immunoglobulins which, despite limiting the growth of pathogenic microorganisms, could however cause harm to the fetus in case of already established pregnancy ( Khanna et al . 2017 , Martelli et al . 2017 ). Based on these considerations and on the high number of failures that occur during infertility treatment, the scientific community has started to consider other health parameters such as maternal periodontal health from the moment of conception. This is partly due to the high percentage of infertility treatments that still fail today, despite the continuous improvements of the procedures ( Khanna et al . 2017 ). The purpose of the present review is to analyze the available literature in order to investigate whether the presence of periodontal disease may affect female conception.

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

It has been estimated that more than 48.5 million couples suffer from infertility and about 40% of these could be attributed to male infertility ( Khanna et al . 2017 ). In recent years, various authors have tried to correlate the presence of poor oral hygiene with the presence of male infertility. It has been established that >30% of male infertility cases are of idiopathic etiology ( Chidambar et al . 2019 ). In a study published in 2014 by Nwhator et al ., a significant correlation was highlighted between the presence of periodontitis and sperm count. Out of 76 subjects analyzed, 55 showed an abnormal sperm count ( Nwhator et al . 2014 ). The results of the present study proved to be in agreement with those of another work published by Klinger et al . in 2011 that evaluated the fertility parameters of male subjects attending in vitro fertilization with the purpose of examining their periodontal health. At the end of that work, the presence of a correlation between periodontitis, low sperm quality and periodontal situation in reference to these subjects in expectation to undergo in vitro fertilization was not excluded. On that occasion, 88% of the participants were found to be suffering from gingivitis or periodontitis and 63% of the total turned out to have an abnormal sperm count ( Klinger et al . 2011 , Khanna et al . 2017 ). Furthermore, in accordance with these considerations, other works ( Prager et al . 2017 , Kellesarian et al . 2018 , Chidambar et al . 2019 , Tao et al . 2020 ) also highlighted a possible link between poor oral hygiene and sperm abnormalities. Pràger et al . in 2017 showed that the extent of gum bleeding and the presence of BOP or calculus could be associated with oligospermia in subjects with idiopathic male infertility ( Prager et al . 2017 ). These results, however, were in contrast to those of a work published in 2016 by Pàsztor et al . at the end of which no type of correlation was highlighted between these two conditions (periodontitis and male idiopathic infertility), and poor periodontal status was not related with any sperm pathology parameters. ( Pasztor et al . 2016 ). In 2018, Kellesarian et al . conducted a literature review, at the end of which the presence of a link between periodontal disease and the presence of male infertility emerged as an eventuality feared by numerous works highlighting the need for further studies and insights ( Kellesarian et al . 2018 ) The results of the present work were therefore found to be in accordance with Chidambar et al . (2019) at the end of which a correlation was found between the number of sites with high loss of clinical attachment and mobility and sperm counts ( Chidambar et al . 2019 ). In 2020, Tao et al . found that male subjects with periodontal disease were more likely to experience abnormalities at the sperm level. The case group, whose participants had some semen abnormality, had a higher incidence of moderate or severe periodontitis compared to the control group ( Tao et al . 2020 ).