International Journal of Research and Review Vol.7; Issue: 8; August 2020 Website: www.ijrrjournal.com Original Research Article E-ISSN: 2349-9788; P-ISSN: 2454-2237

The Relationship between Mycoplasma hominis and Ureaplasma urealyticum Bacterial Infections and Infertility in Women of Reproductive Age Couples

Lili Fitriati Rahmah1, Elizabeth Bahar2, Fika Tri Anggraini3, Andani Eka Putra2

1Magister of Midwifery, 2Department of Microbiology, 3Department of Physiology, Faculty of Medicine, Andalas University, Padang, Indonesia

Corresponding Author: Andani Eka Putra

ABSTRACT Keywords: Infertile, M. hominis, U. urealyticum, Women of Reproductive Age Infertility is a failure to raise children after Couples having approximately 12 months of regular marital contact without using contraception. INTRODUCTION One of the factors that influence infertility is Infertility is defined as a failure to infections including infections of M. hominis raise children after having approximately 12 and U. urealyticum bacteria. This study aimed to months of regular marital contact without determine the relation between M. hominis and using contraception1. Infertility is divided U. urealyticum bacterial infections and infertility in women of reproductive age into two, namely primary infertility, a couples. husband and wife have never had children This research was analytic with case control previously; and secondary infertile, a design of endocervical swab on infertile women husband and wife have had a previous child of reproductive age couples and 33 fertile or wife has been pregnant but abortion, women of reproductive age couple. This ectopic pregnancy, and intra-uterine fetal research was conducted in the Laboratory of death (IUFD) occured2 . Microbiology, Faculty of Medicine, University Globally, in infertility cases of Andalas from March 2019 to April 2020. according to WHO (2012), there were about Then, the sample was tested molecularly. M. 50-80 million couples with infertility. Of hominis and U. urealyticum bacterial infections (30%) were found in developing countries were examined by using PCR with a length of M. hominis product of 509 bp and U. and only (5-8%) in developed countries urealyticum of 429 bp. Data processing was (Masoumi et al., 2013). The prevalence of analyzed statistically by using the chi-square infertility in Asia is (30.8%) Cambodia, test. (10%) Kazakhtan, (43.7%) Turkmenistan, The results showed that in infertile and fertile and (21.3%) Indonesia1. women of reproductive age couples, M. hominis Based on the data from the National was not found, but U. urealyticum was found in Population and Family Planning Agency, infertile and fertile women, but there was no the prevalence of reproductive age couples statistical relation with the infertility in women who do not have children is (9.2%) out of of reproductive age couples, p = 0.091 and OR 11 Districts located in Padang, North value = 0.313. Padang District ranks the highest in The conclusion of this study is that there is no statistical relation between M. hominis and U. reproductive age couples who do not have children at (11, 5%), but the total infertility urealyticum bacterial infections and infertility in 3 women of reproductive age couples data was not found . Factors causing infertility that occur in women include age with an age range of 20-29 years old

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(64.5%) higher than age of 30-39 years old (2009); Du and Zhang, (2010) showed that (20%) and age of 40-49 years old (11.8%), cases of M. hominis bacterial infections in whereas over 50 years (3.7%), menstrual infertile women in Iran were (3.14%), India disorders (20%), tubal disorders (27.4%), (6%) and China (45%). Furthermore, the uterine disorders (9.1%), ovarian disorders results of a study conducted by Michou et al (3.6%), endometrial disease (5%) and (2013) reported that M. hominis bacterium unknown (24.5%) (Roupa et al., 2009; was found in menstrual tissue (13.7%) and Sa'adah and Purnomo, 2016). In addition, cervical mucus (19.5%). While the results of there is (57%) influenced by disorders from the study reported by Sleha et al (2019) women, (17.5%) disorders from men, cases of M. hominis bacterial infection were (4.5%) disorders from men and women and accompanied by U. urealyticum bacterial (21%) unknown cause4 . infection (5.4%)8. M. hominis bacterial Infection of the genitals increases infection is associated with various other the risk of infertility such as viral, fungal, urogenital infections such as bacterial and bacterial infections. Besides consuming vaginosis (BV) and non-specific genital alcohol, Body Mass Index (BMI), and stress infections (IGNS). Cases of M. hominis also affect someone's fertility (Dechanet et bacterial infection in women with BV in al., 2010; Irene, 2010). Infertility is caused Portugal were (30%) and (20%) without by an infection in the reproductive organs BV, Poland were (9.1%) and (59.1%) caused by bacteria Mycoplasma hominis (M. whereas in Papua New Guinea were (7%) hominis), Ureaplasma urealyticum (U. and ( 20%) (Zdrodowska-Stefanow et al., urealyticum), Neisseria gonorrhoeae dan 2006; Dominingues et al., 2003; Clegg et Chlamydia trachomatis5.6 al., 1997). In Indonesia, cases of M. hominis M. hominis and U. urealyticum bacterial infection of 20-30% are the cause bacteria are Mycoplasma sp bacterium of non-gonorrhea urethritis9. The negative found in the human genital tract and their impact of M. hominis bacterial infection on growth increases with the onset of sexual the female reproductive tract which was activity. Mycoplasma sp is a bacterium that firstly identified by Mardh in 1976 in does not have cell walls and belongs to Baczynska et al (2007) with organ culture in gram-positive bacteria. Data on the vitro revealed swelling in the epithelial cells prevalence of M. hominis and U. of the tubal cilia. This resulted in ovum cells urealyticum bacterial infections in abnormal unable to reach the fallopian tubes and meet vaginal secretions in Indonesia is sperm10 tremendously limited. In particular, in M. The mechanism of U. urealyticum hominis bacterial infection, its main risk is bacterium in infecting needs urea as the high-risk sexual behavior which has more energy source. The virulence of U. than one sexual partner, initiating early sex urealyticum bacterium is mediated by IgA and not using condoms (Tibaldi et al., protease, adhesin, urease, phospholipase and 2009). This causes acute urethritis, hemolysin. In vitro, U. urealyticum vaginosis, pelvic inflammatory disease and bacterium is able to form biofilms. Biofilms infertility7. M. hominis bacterium is on high can adhere strongly and resist friction vaginal hydrogen (pH) potential. Normal repeatedly and can increase bacterial low vaginal pH levels turn out to be high immunity so that the body's immune system because the bacterium produces ammonia. is unable to reach the bacteria. The Ammonia is a nutrient for the growth and existence of this biofilm causes chronic propagation of pathogenic microbes. infection because in addition to being Ammonia production by this bacterium difficult to be eliminated by the body, causes a fishy odor in the vagina6 . biofilm is also difficult to be penetrated by The research results reported by anitimicrobial11. Seifoleslami et al (2015); Gupta et al

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U. urealyticum bacterium infects contraceptive protection in less than 12 during sexual intercourse and moves months15. Secondary infertility is a woman towards the upper reproductive tract. This who has previously been pregnant but bacterium can be carried along with sperm abortion or ectopic pregnancy occurs and into the uterus and fallopian tubes and then cannot get pregnant anymore despite having attach to the fallopian tube epithelium, tried for 1 year or more having sexual causing swelling of the cilia and detachment intercourse regularly without contraceptive of the cilia from the epithelium. This protection16. bacterium can avoid the flow of blood by attaching themselves to the surface of the Etiology of Infertility tissue12 Causes of infertility in women can U. urealyticum bacterial infection is be classified into three groups, namely: 25% as a cause of Non Gonococcal Uretritis ovulation disorders, hormonal disorders, (UNG) and often coincides with Chlamydia blockages, local factors17. Risk factors for trachomatis infection. Infection by U. infertility in women include ovulation urealyticum bacterium causes symptoms in disorders, polycystic ovary syndrome, tubal the form of flour albus (43.3%), burning and problems, uterine problems, cervical factors, itching (18.9%), dysuria (10.8%) and no vaginal problems, reproductive organ symptoms (8.1%) (Zdrodowska-Stefanow et infections, sexually transmitted diseases al., 2006). Other studies also report that U. (STDs), hormones, unexplained infertility, urealyticum bacterial infections are in and factors risk of infertility due to infertile (42.5%) and fertile women lifestyle18. For infertile factors in men, (17.4%)13. infertility can also be caused by male, so Infection caused by the two bacteria that examinations in men are important as has bad impact on the female reproductive the part of an infertile examination. Male tract and it needs immediate prevention and fertility can decrease due to congenital or treatment; therefore, the researchers have acquired urogenital abnormalities, conducted a study by examining M. hominis urogenital tract infections, increased scrotal and U. urealyticum bacteria on a molecular temperatures (for example due to basis that aims to determine the possible varicoceles), endocrine abnormalities, causes of infertility in reproductive age genetic disorders and immunological couples. factors. In the UK, 20% of the main causes of infertility are low sperm count or poor LITERATURE REVIEW sperm quality. Impaired semen quality, Infertility is defined as failure to azoospermia and incorrect intercourse are raise children after having approximately 1 the factors that contribute to 50% of infertile year of regular marital contact without using couples (RCOG, 2003). Idiopathic male contraception1. A healthy husband and infertility can be explained by several wife's reproductive system will be able to factors, including endocrine disruption have children. According to Manuaba caused by environmental pollution, free (2012), the husband will produce healthy radicals, or genetic disorders.19 spermatozoa and the wife produces eggs so The handling of infertility is based that spermatozoa and egg cells meet and on two things, namely overcoming the fertilize14. causes of etiology and increasing the According to WHO, in Hestiantoro chances of pregnancy, ovulation disorders, in Anwar et al (2011), the classification of sperm factors, Endomentriosis, Tubal infertility namely primary infertility in factors, Fertilization in vitro (FIV)4. which a woman of reproductive agehas Mycoplasma bacterium is in the class of never been pregnant even though sexual Mollicutes. There are 7 types of intercourse is performed regularly without Mycoplasma that have been isolated from

International Journal of Research and Review (ijrrjournal.com) 17 Vol.7; Issue: 8; August 2020 Lili Fitriati Rahmah et.al. The relationship between mycoplasma hominis and ureaplasma urealyticum bacterial infections and infertility in women of reproductive age couples human genitalia, namely Mycoplasma present on the surface of M. hominis hominis, Mycoplasma genitalium, bacterium. The nature of the diversity of Ureaplasma urealyticum, Mycoplasma antigens is important for adaptation and fermentans, Mycoplasma penetrans, attachment to the host. Meanwhile, the Mycoplasma primatum dan Mycoplasma antigen in the U. urealyticum bacterium is spermatophilum. Mycoplasma is commonly called the Multiple-Banded (MB) antigen. on organs or tissues specifically. U. urealyticum bacterium can be attached to Mycoplasma sp is a bacterium that does not erythrocytes, sperm and urethral have cell walls and is gram-positive20 epithelium26. M. hominis and U. urealyticum U. urealyticum bacterial infections bacteria are bacteria that can be found in the can be found in non-specific genital women urogenital tract in the presence of infections (IGNS) and bacterial vaginosis drastically increased sexual activity21. Both (BV)11. Although U. urealyticum is also of these bacteria can be found in sexually found more in patients with BV, there is no active women22. Infection can occur when statistically significant difference in the colonization is more than 104 CFU/ml23. M. prevalence of patients without BV. So far, hominis and U. urealyticum bacteria are there are still opinion differences about the found more frequently in women with BV role of the U. urealyticum bacterium in than women without BV24. BV27. Infection by the U. urealyticum In a study conducted in Guinea- bacterium causes symptoms in the form of Bissau, Portugal22, it found the prevalence flour albus (43.3%), burning and itching of M. hominis bacterial infection in women (18.9%), and dysuria (10.8%). In 8.1% of with BV who had high-risk sexual behavior women, no symptoms were found23. In was of 30% and U. urealyticum was of addition, in women, U. urealyticum (20%). The prevalence of U. urealyticum bacterium can cause pelvic inflammation, bacterial infections in high-risk women infertility, endometritis, chorioamnionitis, without BV in Poland was (59.1%) and M. premature birth, fetal death, and so forth23. hominis was of (9.1%). In developing countries like Papua New Guinea, the MATERIALS & METHODS prevalence of M. hominis bacterial This is an observational analytic infections in high-risk women was (7%), U. study with a case control research design urealyticum was (20%) and mixed infection that aims to find the relation of risk factors was (65%)23. Mycoplasma sp bacteria are affecting the occurrence of a disease. This distinguished from other types of bacteria research has been carried out at the because of their smallest size (0.2-0.3 μm), Laboratory of Microbiology, Faculty of the absence of cell walls and cell Medicine, University Andalas, from March membranes containing sterols. In its growth, 2019 to April 2020. Endocervial Swab was Mycoplasma sp needs cholesterol taken done on Infertile and Fertile Women in from epithelial cells. The absence of cell Reproductive Age Couples who went to the walls makes Mycoplasma sp resistant to Laboratory of Microbiology, Faculty of antimicrobials that work by interfering with Medicine, University of Andalas. The the synthesis of bacterial walls, such as sample in this study was divided into two penicillin, cephalosporins and groups: Case and Control. The technique vancomycin25. Mycoplasma sp. bacteria used in taking research samples was have the ability to adhere to mucosal consecutive sampling. This Univariate epithelium. This plays an important role for analysis was carried out to see the colonization and causes disease. This proportion of M. hominis and U. attachment ability is due to the presence of urealyticum bacterial infections. Bivariate variable adherence-associated (Vaa) analysis was performed by using the Chi- antigens, specific attachment proteins Square test and then was continued by using

International Journal of Research and Review (ijrrjournal.com) 18 Vol.7; Issue: 8; August 2020 Lili Fitriati Rahmah et.al. The relationship between mycoplasma hominis and ureaplasma urealyticum bacterial infections and infertility in women of reproductive age couples the Odds Ratio (OR) value with a variables are related. If p value is > 0.05, the confidence level of 95% (p = 0.05). Thus, if two variables are not related. the results showed a p value <0.05, the two

RESULTS Table 1 Characteristics of Research Subjects of Reproducive Age Couples Respondent’s Characteristics Infertile Fertile f % f % Age 20-30 Years Old 14 42,4 20 60,6 31-40 Years Old 19 57,6 13 39,4 Total 33 100 33 100 Education Elementary/Junior School 7 21,2 5 15,2 Senior High School 13 39,4 11 33,3 Tertiary Education 13 39,4 17 51,5 Total 33 100 33 100 Occupation Unemployment 14 42,4 17 51,5 Employment 19 57,6 16 48,5 Total 33 100 33 100 Length of Marriage < 5 Years 18 54,5 10 30,3 6-10 Years 11 33,3 14 42,4 > 11 Years 4 12,1 9 27,3 Total 33 100 33 100

Based on the research results (table 1), it was found that the age of 31-40 years old was 57.6% in infertile and 20-30 years old was mostly 60.6% in fertile. From the education level, it obtained that tertiary education (PT) was both 39.4% in infertile and 51.5% in fertile. Furthermore, there were 57.6% of employed women in infertile and 51.5% of unemployed in fertile. Then, the longest marital status was in <5 years which was of 54.5% in infertile and 6- 10 years which was of 42.4% in fertile.

Table 2 Proportion of M. hominis Bacterial Infection with Infertile and Fertile Events in Women of Reproductive Age Couples M. hominis bacterial infection Infertility in women of reproductive age couples Infertile Fertile f % f % Positive 0 0 0 0 Negative 33 100 33 100 Total 33 100 33 100

The isolation of M. hominis and U. urealyticum bacteria from endocervical swabs with molecular scrutiny obtained the following results: Based on the research results (table 2), M. hominis bacterial infection (0%) both infertile and fertile women was not found.

Table 3 Proportion of U. urealyticum Bacterial Infection with Infertile and Fertile Events in Women of Reproductive Age Couples U. urealyticum bacterial infection Infertility in women of reproductive age couples Infertile Fertile f % f % Positive 21 63,6 28 84,8 Negative 12 36,4 5 15,2 Total 33 100 33 100

Based on the research results (table 3), U. urealyticum bacterium in infertile was found of 63.6% and fertile was of 84.8%.

Table 4 Relation between U. urealyticum Bacterial Infection and Infertile and Fertile Events in Women of Reproductive Age Couples U. urealyticum bacterial infection Infertility in women of reproductive age couples OR p Value Infertile Fertile (95%CI) f % f % Positive 21 63,6 28 84,8 0,313 (0,095-1,024) 0,091 Negative 12 36,4 5 15,2 Total 33 100 33 100

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The research subjects obtained the Based on the research results on the relations between U. Urealyticum bacterium education level of women, it obtained that in infertile and fertile namely: Based on the the women with high education in infertility research results (table 4), statistical test were 13 respondents (39.4%), and in results obtained p value > 0.05, namely p = fertility were 17 respondents (51.5%). There 0.091, then statistically, there was no is a relation between education level and significant relation between U. urealyticum infertility because education can influence bacterial infection and infertility in women the process of forming attitudes. In this of reproductive age couples and it obtained case, it is explained that education values (OR= 0,313; CI 95%= 0,095-1,024). influences a person's attitude in dealing with a problem in her life including her DISCUSSION reproductive health problems. A woman Characteristics of Research Subjects who is highly educated is certainly easy to Age accept information relating to maintaining Based on the research results, it was reproductive health so that this change in found that the age of 31-40 years old was attitude makes respondents more concerned more infertile, namely 19 (57.6%) and 20- with reproductive health and avoid various 30 years old of 20 fertile (60.6%). The diseases in the female reproductive organs29. results of this study obtained an average age of infertile and fertile namely 30-35 years Occupation old. Age affects the fertility of a woman Based on the research results, more where the fertile age range is 15-49 years than half of infertile women were employed, old but the peak of fertility is at the age of namely 19 respondents (57.6%); meanwhile, 20-30 years old. At this age, the woman is fertile women who were unemployed were in the reproductive period that still only 17 respondents (51.5%). There is a experiences regular menstruation where the relation between occupation and infertility possibility of getting pregnant is higher than which can be seen from fatigue and stress the increased age. Then, the ability of the caused by the impact of work. Stress ovaries to produce ova has decreased. The experienced by women and stress is related results of this study indicate that there are to hormonal balance. This statement is in women in 31-40 years old experiencing accordance with the theory put forward by infertility; this is in line with the results of Mark Saver on Psychomatic Medicine the study conducted by Shetty et al (2013), which explained that women who have high from 50 infertile women (18%), among of stress levels are less likely to get pregnant them were < 25 years old, (70%) aged 26-35 compared to women who are not stressed. years old, and (12%) above 35 years old. The cause is an imbalance of hormones Meanwhile, the results of the study done by including hormones related to the Muslimin et al (2016), it obtained age <35 reproductive system that can affect the years old of (48%) and age > 35 years old of process of ovulation30 (51.4%). There is a relation between age Several studies have shown that and infertility in women of reproductive one's occupation plays an important role in age. According to Marettih (2012), an infertility. It was found that (54.4%) increase in age will decrease the number of infertile women are women who work full ovum in the ovary so that the ovary is time, (33.3%) women who work part time unable to stimulate the estrogen and and (3.5%) are women as housewives progesterone hormones which affect the (Hammerli et al., 2010). The results of menstrual cycle28. research by Oktarina et al (2014) showed that of 62 infertile women, it found 41 Education people (66.1%) career women and 21 people (33.9%) housewives. The same

International Journal of Research and Review (ijrrjournal.com) 20 Vol.7; Issue: 8; August 2020 Lili Fitriati Rahmah et.al. The relationship between mycoplasma hominis and ureaplasma urealyticum bacterial infections and infertility in women of reproductive age couples research results also prove that working increases dramatically with the beginning of women exposed to infertile risk are of 3.91 sexual activity, having more than one sexual times greater than women as housewives partner and having sexual relations at an and it is statistically significant (OR = 3.91; early age34. There are still doubts about the p = 0.043)31 ability of M. hominis to cause a sexually transmitted infection (STI) singly. A single Length of Marriage infection by M. hominis often does not Based on the research results, more cause any symptoms in infertile women and than half of infertile women who have got many are undiagnosed and untreated34. married for <5 years are (54.5%) and fertile The absence of M. hominis bacterial women who have got married for 6-10 years infection in infertile and fertile women in are (42.4%). this study can be caused by M. hominis is For reproductive age couples who more often found as a co-bacterial get married within the first year of marriage, pathogenesis in various other infectious 84% of women will easily get pregnant if diseases such as bacterial vaginosis, they have regular marital relations without trichomonas vaginalis, Gardnerella using contraception. The pregnancy rate will vaginalis, Chlamydia trachomatis and increase to 92% when the marriage age is Neisseria gonorrhoeae. This is due to the two years. The longer the marriage is, the replacement of lactobacillus sp as a more increasing the chances of women of producer of hydrogen peroxidase (H2O2) in reproductive age couples to get pregnant32. the vagina and is replaced by pathogenic The results of this study are bacteria. The replacement causes a decrease supported by the research by Shetty et al in H2O2 concentration which is generally (2013), showing that 64% of women characterized by the production of a lot of experience infertility for 1-5 years, 32% for vaginal secretions, is gray to yellow, thin, 6-10 years and 4% xperience infertility for homogeneous, fishy and there is an increase 11-15 years. The longer the duration of in pH. Damage caused by these pathogenic infertility experienced by a woman, the bacteria causes pelvic inflammatory disease, more increasing the chance of getting cervicitis and infertility34 pregnant. Couples of less than three years of However, women of reproductive marriage experiencing infertility have a age have a strong main body defense greater chance of getting pregnant33. namely the vaginal mucosal epithelium. In the vagina of a healthy woman, there is glycogen which has purpose to supply Relation between M. hominis Bacterial vaginal ecosystem nutrients. Vaginal Infection and Infertility in Women of epithelial cells break down glycogen into Reproductive Age Couples monosaccharides which are then converted Based on the research results on the by Lactobacillus bacteria into lactic acid. In relation between M. hominis bacterial the internal female reproductive tract, there infection and infertility, it showed that are three different surfaces for protection infertile women did not have M. hominis against infection, namely the cervix, uterine bacterial infection as well as in fertile wall or endometrium, and fallopian tubes35. women. It cannot be concluded because the Mucosal epithelium in the chi-square test cannot be performed because reproductive organs is a component of the the result obtained is (0%) meaning that the mucosal immune system that is connected result of this study was not statistically from cells and tissues and functions as a significant. complex immune defense mechanism on the M. hominis bacterium is an mucosal surface. Mediators in systemic opportunistic pathogenic bacterium in immunity also penetrate into the human. The growth of this bacterium

International Journal of Research and Review (ijrrjournal.com) 21 Vol.7; Issue: 8; August 2020 Lili Fitriati Rahmah et.al. The relationship between mycoplasma hominis and ureaplasma urealyticum bacterial infections and infertility in women of reproductive age couples reproductive tissue and secretions to protect geographical, social, cultural and religious the local immune response of the mucosa35. locations. In 2008, there were an estimated There are a large number of immune 498.9 million sufferers of new STIs in and lymphatic system cells in the female developing countries such as Africa, Asia, reproductive system that are able to Southeast Asia37. eliminate M. hominis bacterium that enters The high incidence of M. hominis the vagina because this bacterium grows and infection among fertile women in these develops slowly within 1-4 days so that its countries proves that they are free to have growth can be inhibited by specific sexual relations and to change partners. This immunity namely B lymphocytes and T is according to Menon et al (2016) stating lymphocytes. B lymphocytes produce that free sexual behavior with many sexual antibodies that function as a defense against partners significantly increases the risk of extracellular infections, viruses and bacteria various infections including M. Hominis and neutralize the toxin; while T bacterium38. lymphocytes consist of helper T cells (Th) Differences in results of this study can and cytotoxic T (Tc) cells. These helper occur due to differences in the number of (Th) T cells will release IFN cytokines γ samples and in this study, clinical data which will activate macrophages and kill the collection was not performed such as M. hominis bacteria and stimulate the women with a history of pelvic growth and development of B lymphocytes; inflammatory disease, menstrual cycle while T cells (Tc) play a role in lysis of regularity, weight, sexual history, obstetric epithelial cells infected by M. hominis history, hormone examination, follicles bacterium36. examination at ovulation, and husband Likewise, cervix has squamous semen analysis. epithelium which is continuously replaced This type of research is still rarely by cells in the basal layer and secretes done in Indonesia so that the number of mucus that contains various antimicrobials sufferers of M. hominis infection in infertile that protect against M. hominis infections women still cannot be reported. In West which are known that the bacterium is Sumatra region, Padang in particular, there considered pathogenic, but is asymptomatic. is no research conducted yet to find out the Several other studies prove that the number of sufferers and the relation presence of M. hominis bacterium in between M. hominis infection that can affect infertile women is significant to the infertility in women of reproductive age. influence and damage to the reproductive There are some weaknesses that organs, namely the uterus, endometrium and occur during the study, such as the number fallopian tubes. However, based on the of samples that are too small, so it is results of study found by yje researchers, M. difficult to know the prevalence of M. hominis was not found in endocervical swab hominis infection in infertile women. examination in infertile women of Furthermore, the researchers have limited reproductive age couples. This explains that time. In addition, many other factors are not women who experience infertility are not examined related to infertility in women of caused by this bacterium. This can be from reproductive age couples. hormonal disorders, ovarian disorders, ovulation disorders, and even factors from Relation between of U. urealyticum men. Bacterial Infection and Infertility in In the results of this study, according Women of Reproductive Age Couples to the researchers, the situation shows that The results of the study showed that there are many differences that occur in more than half of infertile women of abroad life compared to Indonesia, reproductive age had U. urealyticum especially in Padang. This is influenced by bacterial infections with 21 respondents

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(63.6%) and more than 28 respondents with This study explains that not only U. fertile women (84.8%). Statistical test urealyticum bacterial infection which can results obtained p value > 0.05, namely p = cause infertility in women, but many factors 0.091. It can be concluded statistically that can influence it. As explained above, there there is no significant relation between U. are factors of age, education, occupation, urealyticum bacterial infection and length of marriage including psychological infertility in women of reproductive age stress40. couples. The value is (OR = 0.313; 95% CI The results of the study conducted = 0.095-1.024). by the researchers found that not only Infection caused by U. urealyticum infertile women (cases) who were infected bacterium is found in the women urogenital by the U. urealyticum bacterium, but also tract and the prevalence of this bacterium fertile (control) women also experienced can reach 80% in normal people, but these bacterial infections. In this study, there increases because of changing sexual are limited samples and many other factors partners, low socioeconomic status, that cause the spread of U. urealyticum smoking and the use of contraceptives in the bacterial infections, namely decreased body womb (AKDR11. immunity, the ability of these bacteria to U. urealyticum bacterial infection avoid the immune system, hot climate, enters through the ascending pathway and vaginal douching, use of vaginal antiseptics moves to the upper reproductive tract. Due and sexually transmitted infections. to the influence of hormonal changes during Theories and results of other studies ovulation and menstruation, it causes non- prove that U. urealyticum bacterium is a pathogenic organisms to overgrow and microorganism found in the urogenital tract move upwards. Opening of the cervix of healthy women when sexual activity during menstruation and sexual intercourse begins, having early sexual intercourse can cause infection facilitating the without using a condom, and habit of ascending movement of microorganisms. changing sexual partners. Thus, these Bacteria can be carried along with sperm bacteria are able to enter and survive in the into the uterus and fallopian and then attach bloodstream, countering normal defense to fallopian tube epithelium which causes mechanisms, including antibodies, swelling and damage to the cilia and complement, and transferrin. The results detachment of the cilia from the showed that living in the hot tropics makes epithelium39. us sweat frequently. This sweat makes our Based on in vitro, U. urealyticum body moist, especially sexual and bacterium is able to form biofilms. Biofilms reproductive organs that are closed and consist of bacterial cells that are densely folded. As a result, bacteria are easily breed arranged along with an extracellular matrix and the ecosystem in the vagina is disturbed, so that the body's immune system is unable causing unpleasant odors and infections41. to reach the bacteria. The existence of this biofilm causes chronic infections because in CONCLUSION addition to being difficult to be removed by Based on the research results on M. the body, it is also difficult to be penetrated hominis and U. urealyticum bacterial by antimicrobials11. This is because biofilms infection and infertility and fertility in can increase the tolerance of bacteria to women of reproductive age couples, it can harmful environmental conditions. These be concluded that in research subjects, M. bacteria can be avoided, carried away and hominis bacterium is not found on fertile separated from the flow of water or blood and infertile women of reproductive age by attaching themselves to the surface of the couples. In more than half of infertile tissue. Biofilms can be strongly attached to women of reproductive age couples, U. and resist repetitive friction12. Urealyticum bacterium is found. In the

International Journal of Research and Review (ijrrjournal.com) 23 Vol.7; Issue: 8; August 2020 Lili Fitriati Rahmah et.al. The relationship between mycoplasma hominis and ureaplasma urealyticum bacterial infections and infertility in women of reproductive age couples event of M. hominis bacterial infection, 10. Baczynska, A. Funch, P. Fedder, J. there is no significant relation in infertile Knudsen, HJ. et al., (2007). Morphology of women of reproductive age couples (p> human Fallopian tubes after infection with 0.05). Besides, in the event of U. Mycoplasma genitalium and Mycoplasma urealyticum bacterial infection, there is no hominis-in vitro organ culture study. Hum Reprod. vol. 22, pp. 968-979. significant relation with infertility in women 11. Juhasz, E. Ostorhazi, E. Ponyai, K. Sillo, P. of reproductive age couples (P > 0.05). et al., (2011). Ureaplasma: From Commensal Flora to Serious Infections. REFERENCES Reviews in Medical Microbiology. vol. 22, 1. World Health Organization. (2013). pp. 73-83. Factsheet of Sexuallty Transmitted 12. Rabin, N. Zheng, Y. Temeng, CO. Du, Y. et Infections (STI’s) al., (2015). Biofilm formation mechanisms http://www.who.int/reproductivehealth/publ and targets for developing antibiofilm ications/rtis/rhr13_02/en/. (28 April 2020) agents. Future Med Chem. vol. 7, no. 4. pp. 2. Ahsan. (2012). Faktor Risiko Yang 493-512. Memengaruhi Keterlambatan Konsepsi 13. Yuwono, T. (2006). Teori dan Aplikasi (Infertlitas) Pasangan Suami Istri Pada Polymerase Chain Reaction. Yogakarta: Laki-Laki Di Kecamatan Palu Utara Kota Andi Offset. 58 Palu. Skripsi. Universitas Hasanuddin. 14. Manuaba. (2012). Ilmu Kebidanan, Penyakit Makassar kandungan dan KB. Penerbit buku 3. Badan Pusat Statistik Jakarta Pusat, (2011). kedokteran. Jakarta: EGC. Pedoman Pendataan Survei Sosial Ekonomi 15. Hestiantoro, A. Infertilitas dalam : Anwar, Nasional Tahun 2011. Jakarta Pusat: Badan M. Baziad, A. Prabowo, RP (2011). Ilmu Pusat Statistik kandungan edisi Ketiga: Jakarta : PT Bina 4. Aizid, R. (2010). Mengatasi Infertilitas Pustaka Sarwono Prawirohardjo. hal: 425- Kemandulan Sejak Dini. Yogyakarta: 35 Flasbook 16. Saragih, CF. (2014). Analisa Faktor-Faktor 5. Gershon, A. (1998). Rubella (German Penyebab Infertilitas Di Rs Jejaring Measles). In : Fauci AS, Martin JB, eds. Departemen OBGIN FK USU Periode Harrison Principles of Internal Medicine. Januari 2012 - Desember 2013. Tesis. New York. Mc Graw-Hill. vol 3, no.4 Universitas Sumatera Utara 6. Cedillo-Ramirez, L. Gil, C. Zago, I. Yanez, 17. Miller. Boyden. Frey, KA. (2007). A. et al., (2000). Giono S. Association of Infertility. Am Fam Physician. vol. 75, no. 6 Mycoplasma hominis and Ureaplasma 18. Aizid, R. (2010). Mengatasi Infertilitas urealyticum with some indicators of Kemandulan Sejak Dini. Yogyakarta: nonspecific vaginitis. Rev Latinoam Flasbook Microbiol. vol. 42, no.1. pp. 1-6. 19. European Association of Urology (EAU). 7. Taylor-Robinson, D. (2012). The role of (2010). Guidelines on male infertility. mycoplasmas in non-gonococcal urethritis: 20. Goulet, M. Dular, R. Tully, JG. Billowes, G. a review. The Yale journal of biology and et al., (1995). Isolation of Mycoplasma medicine. vol. 56, no. 5. pp. 537-543 pneumoniae from the human urogenital 8. Sleha, R. Bostikova, V. Hampl, R. Salavec, tract. Journal Clinical Microbiology. vol. M. et al., (2019). Prevalence of Mycoplasma 33, no. 11. pp. 2823-2825. hominis and Ureaplasma urealyticum in 21. Baka, S. Kouskouni, E. Antonopoulou, S. et women undergoing an initial infertility al., (2009). Prevalence of Ureaplasma evaluation. Epidemiol Mikrobiol Imunol. urealyticum and Mycoplasma hominis in vol. 65, no. 4 pp. 232-237 women with chronic urinary symptoms. 9. Garcia-Castillo, M. Morosini, MI. Galvez, Urology. vol. 74, no. 1. pp. 62-66. M. Baquero, F. et al., (2008). Differences in 22. Domingues, D. Tavora, TL. Duarte, A. biofilm development and antibiotic Sanca, A. et al., (2003). Genital susceptibility among clinical Ureaplasma mycoplasmas in women attending a family urealyticum and Ureaplasma parvum planning clinic in Guine-Bissau and their isolates. Journal Antimicrob Chemother. susceptibility to antimicrobial agents. Acta Vol. 62, no. 5. pp. 1027-1030. Trop. vol. 86, no. 1. pp. 19-24.

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