REVIEW ARTICLES

Oral health status and fertility treatment – a bidirectional connection

 Sănătatea orală şi tratamentele pentru fertilitate – o asociere bidirecţională

First published: 30 aprilie 2023

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/ObsGin.71.1.2023.8134

Abstract

This article summarizes the most recent research connecting reproductive therapy with oral health, focusing on periodontal diseases. Oral health is a component of overall health and carries multiorgan implications, therefore it is anticipated that what influences the whole body will affect oral health. Moreover, oral health status influences the reproductive system’s health and the fertility treatments outcome. We emphasize this bidirectional relationship between oral health and reproductive therapy, especially if hormone levels vary.
 

Keywords
oral health, women, fertility treatment, periodontal diseases

Rezumat

Cercetări recente evidenţiază existenţa unei relaţii bidirecţionale între terapia reproductivă şi sănătatea orală, în special cea parodontală. Sănătatea orală este o componentă a sănătăţii generale şi este afectată de modificările care apar în întregul organism, precum şi de cele produse de terapia reproductivă. Astfel, variaţiile nivelurilor hormonale produc modificări orale în special asupra statusului parodontal. În plus, starea sănătăţii parodontale este un factor care influenţează sănătatea sistemului reproducător, precum şi rezultatul tratamentelor de fertilitate.
 

Introduction

Oral health is a parameter of overall health and encompasses a variety of diseases and conditions, including dental diseases, periodontal diseases, teeth loss, orodental trauma, oral mucosal lesions, oral cancer, and birth defects such as cleft lip and palate. The use of cigarette products, alcohol addiction and unhealthy diets high in free sugars are all risk factors for oral diseases(1).

Certain aspects of reproductive therapy influence the oral cavity’s status, mainly the elevated ovarian hormone levels. Additionally, several studies have connected periodontal disease to unfavorable reproductive outcomes such as infertility in men and women, preterm delivery, low birth weight, fetal growth restriction, preeclampsia and perinatal death(2). The inability to conceive despite one or more years of attempts for natural fertilization is referred to as infertility. Since it is found in about 50% of women in developing countries, infertility is a prevalent serious condition that burdens many families(3).

The treatment options for infertility vary from life­style behavior changes, ovulation tracking, luteal phase support, intrauterine insemination and ovulation induction to in vitro fertilization. Most of these methods are associated with the administration of fertility drugs.

In the following, we discuss the bidirectional connec­tion between infertility treatments and oral health status.

Lifestyle factors

In both men and women, lifestyle factors and environmental conditions, such as age, obesity (Body Mass Index ≥30 kg/m2), diet (saturated fats and sugar) and exposure to pollutants, play a significant role in determining infertility and becoming a widespread issue(4).

Age-related declines in oocyte quality and ovarian reserve in women begin at about 25 to 30 years old(5). In men, the reproductive timeline shows variations caused by testosterone reduction. Semen parameters such as volume and motility decrease at the age of 35(3).

Both fertility and oral health are benefits of a healthy diet. In women, it influences ovulation, and in men, the semen quality(3).

Abuse of smoking, using illegal drugs, and drinking alcohol and caffeine can all have a harmful impact on fertility and oral health(3). Smoking can cause rapid ovarian reserve depletion, delayed conception in women, and reduced semen motility and morphology in men. Regarding oral health, tobacco usage increases the risk of developing periodontitis, peri-implantitis, caries, alveolar osteitis and halitosis(6). Additionally, smoking is etiologically linked to potentially malignant lesions and malignant tumors of the oral mucosa.

Ovarian induction is an infertility treatment that employs drugs to stimulate egg development and release, or ovulation. This therapy induces the hypothalamus to release the gonadotropins necessary for follicle growth and ovulation. The agents include clomiphene citrate, aromatase inhibitors, gonadotropins such as follicle-stimulating hormone, and human menopausal gonadotropin. The results of this therapy have shown elevated serum levels of estrogen, progesterone and other hormones, which also interact with the gingival vascular system, depress cell-mediated immune res­ponse and influence the subgingival flora. A clinical study with a combined protocol of drugs found that ovarian induction increases gingival inflammation, bleeding and gingival crevicular fluid(7). Moreover, the timing of drug intake was associated with the severity of gingival-periodontal damage(7).

Luteal-phase support is an intervention used for assisted reproduction technology cycles. It uses dif­ferent formulations of hormonal products based on progesterone supplements, recombinant luteinizing hormone human chorionic gonadotropin, estradiol and gonadotropin-releasing hormone agonists(8).

Intrauterine insemination (IUI) – a less intrusive, less stressful and cheaper infertility treatment – can offer a respectable success rate for up to three or four attempts. This procedure involves injecting a small amount of prepared semen directly into the uterine cavity at or near the anticipated ovulation period. Controlled ovarian stimulation and luteal phase support treatment can be used during IUI or not(9).

In vitro fertilization (IVF) is a treatment option for infertility with an implantation rate that ranges from 25% to 40%(10). With IVF, the ovaries can generate more eggs than usual, which are then harvested and fertilized with sperm outside the body in a laboratory to form embryos. This treatment also uses fertilization drugs.

Pavlatou et al. reported worsening periodontal clinical parameters, increased bleeding, and gingivitis in women undergoing IVF treatment(11). The authors found qualitative or quantitative changes when analyzing subgingival microbial flora during IVF(11). Another study of 34 Lebanese women undergoing controlled ovarian stimulation with IVF treatment reported no association between periodontal disease and poor IVF outcomes(12).

Impact of periodontal diseases
on fertility treatment

Variation in hormonal levels is associated with gingival and periodontal diseases. In pregnancy, women’s gingiva is affected by estrogen, progesterone and chorionic gonadotropin through vascular changes such as endothelial cell enlargement, platelet and granulocyte adhesion to vessel walls, microthrombus development, disruption of perivascular mast cells, enhanced vascular permeability and vascular proliferation. Additionally, estrogen can promote fibrous collagen synthesis and maintenance as well as the cytodifferentiation of oral epithelium. The increased folate metabolism in oral mucosa, which can deplete folate reserves and prevent tissue regeneration, is another effect of sex steroid hormones(13). Elevated hormone levels are linked to most fertility treatments. According to these findings, the most prevalent oral signs induced by raised ovarian hormone levels are increased gingival inflammation and exudate(14). The ability of gingival healing is decreased by progesterone via altering the rate and pattern of collagen formation(14).

According to Machado et al., Portuguese women who were referred for fertility treatment had worse periodontal metrics than women from a representative control sample(15). The authors noted that, because these women had other priorities (seeking fertility), the existence of periodontal disease did not negatively impact their quality of life with regard to oral health.

A preconception prospective cohort study including 2764 North American female pregnancy planners indicated that self-report measures of periodontitis might be associated with lower fecundability(16).

Numerous studies have linked periodontal disease to unfavorable pregnancy results, including preterm birth, low birth weight, miscarriage or early pregnancy loss and preeclampsia(11). Two hypotheses can explain these observations: oral bacteria are transmitted through the blood (altering implantation, adhesion and embryo invasion), or the fetus is harmed by a high level of cytokines and immunoglobulins produced in periodontal diseases(17). There is a relationship between periodontitis and conditions related to infertility in women, such as polycystic ovarian syndrome, endometriosis, bacterial vaginosis and obesity(18).

According to a meta-analysis, women with polycystic ovarian syndrome are 28% more likely to develop periodontitis, whereas women with periodontitis are 46% more likely to develop polycystic ovary syndrome(19). The spread of bacteria from periodontitis, with a subsequent subclinical inflammatory reaction, affects the endo­crine system and decreases fertility. Periodontal tissue is altered by the hormonal and inflammatory effects of the polycystic ovarian syndrome. Nevertheless, these disorders are connected in both directions, but no proof of a genetic link was found between them(20).

A systematic review analyzing male infertility and dental health status reported a positive relationship between male infertility and oral diseases: caries, necrotic pulp and/or chronic periodontitis. And the severity of these oral diseases – also related to smoking habits and oral hygiene practice – may also be associated with the deterioration in sperm parameters(21). In addition, two studies have linked paternal periodontal disease and infertility: one found a connection between chronic periodontitis and low sperm counts(22), while the other found that deep periodontal pockets tended to be positively correlated with low sperm motility(23).

Dental health status and infertility

A systematic review of seven studies indicated a connection between male infertility and poor tooth health(21). A case-control study involving 100 women (50 fertile women and 50 unexplained infertile women) detected no statistical difference between decayed, missing and filled teeth, plaque index, and gingival recession values between groups. Women with unexplained infertility had a higher rate of advanced caries, and the periodontal profile was poor compared to the fertile group(24).

Conclusions

Oral health status and fertility have a two-way relationship in both women and men. Reproductive therapy influences women’s gingiva and periodontal tissues by aggravating a preexistent condition. The etiology of infertility can be affected by oral foci of decayed teeth and periodontitis. 

Conflict of interest: none declared  
Financial support: none declared
This work is permanently accessible online free of charge and published under the CC-BY. 

Bibliografie

  1. Who.int. 2022. Oral health. [online]. Available at: https://www.who.int/health-topics/oral-health#tab=tab_1 [Accessed 4 October 2022].

  2. Rashidi Maybodi F, Amirzade Iranaq MH. Poor oral health and fertility problems: A narrative mini-review. Journal of Midwifery and Reproductive Health. 2017;5(1):849-854.

  3. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. 2013;11:66. doi: 10.1186/1477-7827-11-66.

  4. Panth N, Gavarkovs A, Tamez M, Mattei J. The Influence of Diet on Fertility and the Implications for Public Health Nutrition in the United States. Front Public Health. 2018;31;6:211. doi: 10.3389/fpubh.2018.00211.

  5. Silvestris E, Lovero D, Palmirotta R. Nutrition and Female Fertility: An Interdependent Correlation. Front Endocrinol (Lausanne). 2019;10:346. doi: 10.3389/fendo.2019.00346.

  6. Ford PJ, Rich AM. Tobacco Use and Oral Health. Addiction. 2021;116(12):3531-3540. doi: 10.1111/add.15513.

  7. Haytaç MC, Cetin T, Seydaoglu G. The effects of ovulation induction during infertility treatment on gingival inflammation. J Periodontol. 2004;75(6):805-10. doi: 10.1902/jop.2004.75.6.805.

  8. Dashti S, Eftekhar M. Luteal-phase support in assisted reproductive technology: An ongoing challenge. Int J Reprod Biomed. 2021;19(9):761-772. doi: 10.18502/ijrm.v19i9.9708.

  9. Tang Y, He QD, Zhang TT, Wang JJ, Huang SC, Ye Y. Controlled ovarian stimulation should not be preferred for male infertility treated with intrauterine insemination: a retrospective study. Reprod Biol Endocrinol. 2021;19(1):45. doi: 10.1186/s12958-021-00730-3.

  10. Zhang J, Wang C, Zhang H, Zhou Y. Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review. Reprod Biol Endocrinol. 2021;19(1):142. doi: 10.1186/s12958-021-00824-y.

  11. Pavlatou A, Tsami A, Vlahos N, Mantzavinos T, Vrotsos I. The effect of in vitro fertilization on gingival inflammation according to women’s periodontal status: clinical data. J Int Acad Periodontol. 2013;15(2):36-42.

  12. Khalife D, Khalil A, Itani MN, Khalifeh F, Faour S, Salame A, Ghazeeri G. No association between the presence of periodontal disease and poor IVF outcomes: a pilot study. Int J Womens Health. 2019;11:363-370. doi: 10.2147/IJWH.S202135.

  13. Markou E, Eleana B, Lazaros T, Antonios K. The influence of sex steroid hormones on gingiva of women. Open Dent J. 2009;3:114-9. doi: 10.2174/1874210600903010114.

  14. Zachariasen RD. The effect of elevated ovarian hormones on periodontal health: oral contraceptives and pregnancy. Women Health. 1993;20(2):21-30. doi: 10.1300/J013v20n02_02. 

  15. Machado V, Botelho J, Proença L, Mendes JJ. Comparisons of Periodontal Status between Females Referenced for Fertility Treatment and Fertile Counterparts: A Pilot Case-Control Study. Int J Environ Res Public Health. 2020;17(15):5281. doi: 10.3390/ijerph17155281.

  16. Bond JC, Wise LA, Willis SK, Yland JJ, Hatch EE, Rothman KJ, Heaton B. Self-reported periodontitis and fecundability in a population of pregnancy planners. Hum Reprod. 2021;36(8):2298-2308. doi: 10.1093/humrep/deab058.

  17. Ludovichetti FS, Signoriello AG, Gobbato EA, Artuso A, Stellini E, Mazzoleni S. Can periodontal disease affect conception? A literature review. Reprod Fertil. 2021;2(1):R27-R34. doi: 10.1530/RAF-20-0043.

  18. Ricci E, Ciccarelli S, Agnese Mauri P, et al. Periodontitis, female fertility and conception (Review). Biomed Rep. 2022;17(5):86. doi:10.3892/br.2022.1569.

  19. Wadia R. Polycystic ovarian syndrome & periodontitis. Br Dent J. 2020 Jul;229(2):125. doi: 10.1038/s41415-020-1953-4.

  20. Wu P, Zhang X, Zhou P, Zhang W, Li D, Lv M, Liao X. Assessment of Bidirectional Relationships Between Polycystic Ovary Syndrome and Periodontitis: Insights from a Mendelian Randomization Analysis. Front Genet. 2021 Mar 26;12:644101.

  21. Kellesarian SV, Yunker M, Malmstrom H, Almas K, Romanos GE, Javed F. Male Infertility and Dental Health Status: A Systematic Review. Am J Mens Health. 2018;12(6):1976-1984. doi: 10.1177/1557988316655529.

  22. Nwhator SO, Umeizudike KA, Ayanbadejo PO, Opeodu OI, Olamijulo JA, Sorsa T. Another reason for impeccable oral hygiene: oral hygiene-sperm count link. J Contemp Dent Pract. 2014 May 1;15(3):352-8. doi: 10.5005/jp-journals-10024-1542.

  23. Klinger A, Hain B, Yaffe H, Schonberger O. Periodontal status of males attending an in vitro fertilization clinic. J Clin Periodontol. 2011;38(6):542-6. doi: 10.1111/j.1600-051X.2011.01720.x.

  24. Yildiz Telatar G, Gürlek B, Telatar BC. Periodontal and caries status in unexplained female infertility: A case-control study. J Periodontol. 2021;92(3):446-454. doi: 10.1002/JPER.20-0394.