Scilit | Article - Genital tract infection and associated factors affect the reproductive outcome in fertile [...] (2023)

Scilit | Article - Genital tract infection and associated factors affect the reproductive outcome in fertile [...] (1)

Genital tract infection and associated factors affect the reproductive outcome in fertile females and females undergoing in vitro fertilization

Dimitra Moragianni, George Dryllis, Panagiotis Andromidas, Rachil Kapeta-Korkouli, Evangelia Kouskouni, Ilias Pessach,

, Antigoni Kodonaki, Nikolaos Athanasiou, Avraham Pouliakis,

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Abstract: Assisted reproductive techniques including in vitro fertilization (IVF) are being used increasingly worldwide and screening for genital tract infections (GTIs) is recommended prior to treatment as their presence may affect the success rate of IVF. The current study aimed to assess the possible associations between GTI‑associated factors and reproductive outcome in a group of reproductive age fertile females and infertile females receiving IVF. A total of 111 infertile women enrolled in an IVF programme (Group A) and 104 fertile women (mothers of at least one child; Group B) underwent microbiological screening of vaginal and cervical samples. All samples were cultured using different protocols for aerobic pathogens, bacterial vaginosis (BV), Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis and human papilloma virus (HPV). Although each group were comparable in age, more infertile women were >30 years (P=0.0064), had a higher education level (P=0.0001) and were smokers (P=0.007). Only BV (P=0.0013) was more prevalent in Group A. Of the 111 infertile females who were scheduled for IVF, 32 females had a successful pregnancy (Group C) and 79 females exhibited IVF failure (Group D). Tubal factor (P=0.012), estradiol‑2 (E2) levels Introduction Genital tract infections (GTIs) frequently occur in females of reproductive age and are strongly associated with increased morbidity, including diseases such as urethritis, pelvic inflammatory disease, amniotic fluid infection and preterm deliveries in pregnancy (1,2). Pelvic inflammatory disease involves the infection and inflammation of the upper genital tract (endometrium, fallopian tubes, ovaries and pelvic peritoneum), which may result in infertility, ectopic pregnancy and chronic pelvic pain (3,4). The vaginal microflora is a dynamic ecosystem normally inhabited by lactobacilli. These bacteria support healthy vaginal conditions by maintaining an acidic environment that is inhospitable to other pathogenic microorganisms. Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii and Lactobacillus iners are considered to be the four major vaginal Lactobacillus species (5). Many important aspects of women's sexual and reproductive health rely on the protective role of lactobacilli in the vaginal environment. The composition of the vaginal microflora is not static but changes over time in response to various endogenous and exogenous influences. The most common alteration in vaginal microflora is a condition named bacterial vaginosis (BV) (6). According to the United States Public Health Service, the incidence of BV is ~30% in females of reproductive age (7). Additionally, the reported incidences of Candida, Mycoplasma and Ureaplasma infections, which are associated with infertility, have increased (8,9). The most common urogenital tract infections associated with infertility are aerobic pathogens, BV, Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis and human papilloma virus (HPV) (1-4,7-9). The impact of certain bacteria on fertility, including Chlamydia trachomatis, Neisseria gonorrhoeae and Ureaplasma urealyticum has been well established (8-10). Furthermore, Chlamydia trachomatis infection may cause pelvic inflammatory disease, resulting in chronic pelvic pain, ectopic pregnancy and infertility (10). Infertility affects ~15% of couples worldwide (11). Human infertility is defined as the inability for a couple to conceive and produce offspring following at least 12 consecutive months of unprotected sexual intercourse (11). Infertility is a complex condition as it may alter the quality of life in couples. In 2010, ~1.9 and ~10.5% of women at reproductive age (20-44 years old) were affected by primary and secondary infertility respectively (11). According to the World Health Organization, the term 'primary infertility' is applied when a woman has not conceived (12). 'Secondary infertility' is the incapability to conceive in a couple who have had at least one previously successful conception (12). There are several causes for this condition, among which urogenital infections serve an important role (13). In vitro fertilization (IVF) has been utilized worldwide to reduce the rate of infertility. It provides a novel means of preliminary genetic diagnosis and maintenance of fertility, making IVF is the most effective treatment option for couples with multifactorial infertility problems (11,13). Fertility rate, defined as the total number of infants born by a single female in her lifetime, has been estimated to be 2.1(14). It has also been observed that ~10-15% of Greek couples experience infertility issues (14). Furthermore, previous studies have indicated that a history of GTI may be associated with IVF failure (11-18), although supporting data remains sparse. The aim of the current study was to evaluate potential GTI-associated predictors of infertility in Greek females and to assess the factors associated with successful or unsuccessful IVF technique in infertile patients. Materials and methods Patients The current study was prospectively designed and performed at the Department of Microbiology, Aretaieion General Hospital, National and Kapodistrian University of Athens, from January 2012 to December 2017. A total of 125 Greek females of reproductive age (range, 22-45 years; median age, 32), undergoing vaginal/cervical fluid examination as prenatal screening were recruited into the present study. Patients were classified into two groups: 111 infertile females enrolled into an IVF program (group A) and 104 fertile females (having at least one child; Group B; considered to be the control). Epidemiologic data, symptoms and GTIs were compared between groups. Induction of ovulation and fertilization In all patients receiving IVF, a long ovulation induction protocol was applied, which included the daily nasal administration of gonadotropin releasing hormone (2 mg/ml; Synarela®; Pfizer, Inc., New York, NY, USA) on the 21st day of the pre-treatment cycle, which included the administration of combined oral contraceptives (0.03 mg ethinyl estradiol and 3 mg drospirenone; each, Yasmin®; Bayer Hellas AG, Athens, Greece) administered for 2 to 4 weeks. Following the downregulation of estradiol-2 by the aforementioned drugs (E2; <50 pg/ml) recombinant follicle stimulating hormone (FSH) was administered subcutaneously (beta-follitropin; Puregon®; Organon International BV, OSS, The Netherlands) in a daily dose of 75-300 IU (depending on the patient's characteristics). When ≥3 follicles of 18 mm in diameter were detected via a trans-vaginal ultrasound, 10,000 IU of human chorionic gonadotropin (hCG) was administered subcutaneously (Pregnyl®; Organon International BV) and oocyte pick-up was performed transvaginally via a thin needle 35-36 h later, under ultrasonography. Following oocyte removal, blood-free follicular fluid samples were centrifuged at 600 x g for 10 min, at 25˚C and supernatants were stored at -80˚C. The in vitro fertilization of oocytes was accomplished using the spermatozoa of the patient's respective husband and all embryo transfers were performed on day 3 with a Wallace catheter under ultrasound guidance. Patient characteristics Patients in group A were assessed for IVF success and for potential predictors of failure. Patients that successfully became pregnant (Group C; 32 patients) were compared with patients unable to achieve pregnancy (Group D; 79 patients) in regards to the type of pathogen isolated In patients scheduled for IVF, basic characteristics including E2 levels, the number of oocytes retrieved, the number of oocytes fertilized and the number of transferred embryos were recorded. Serum E2 levels (centrifuged at 600 x g for 10 min at 25˚C) were measured using the Abbott Architect i-1000SR auto-analyzer (Abbott Pharmaceutical Co., Ltd., Lake Bluff, IL, USA; sensitivity, 10 pg/ml; intra-assay and inter-assay coefficients of variability, 5.5 and 6.7%, respectively). Additionally, factors contributing to infertility including endometriosis, male factor (male infertility) or tubal factor (anatomical disorders) were reported. Vaginal discharge examination In all patients, specimens of vaginal discharge were obtained from the posterior fornix for microscopy, amine testing, and gram staining at 25˚C for 5 min. Solution A (90% Crystal violet; 20 ml of 95% Ethanol) and Solution B (0.8 g Ammonium oxalate with 80 ml Distilled water) were mixed to obtain a crystal violet staining reagent. Samples were stored for 24 h at 25˚C and filtered through paper prior to use. At the completion of the Gram Stain, gram-negative bacteria stained pink/red and gram-positive bacteria stained blue/purple. Patients from which vaginal samples were not collected were excluded from the current study. Amine testing (‘whiff’ test) was performed by adding a drop of potassium hydroxide 10% to vaginal discharge samples. The test was considered positive if the typical fishy odor was produced. A gram-stained smear was examined via light microscopy (magnification, x1,000) and the presence of yeast and leukocytes was also determined. Specimens for yeast culture, were incubated at 37˚C for 24-48 h and placed in modified Stuart's medium and plated on Sabouraud dextrose agar (both from BioMerieux, Marcy l’Etoile, France). Vaginal samples were cultured for aerobic pathogens at 37˚C for 24-48 h and the automated system VITEK2 (BioMerieux) was used to identify the pathogens present. BV diagnosis BV was diagnosed via the Nugent scoring system (19). This method assesses the quantity of three different bacterial morphotypes: Large gram-positive rods (representing lactobacilli), small gram-variable rods (representing Gardnerella and Bacteroides/Prevotella species) and curved rods (representing the Mobiluncus species). On the basis of these results, samples were assigned a score from 0 to 10, with 1-3 being considered as normal, 4-6 being considered as intermediate bacterial count (where patients receive chemoprophylaxis treatment) and 7-10 being considered as BV. BV diagnosis was further verified using the Amsel criteria (20), which includes the presence of at least three of the following four findings: homogeneous vaginal discharge, vaginal pH >4.5, ‘fishy’ odour on addition of potassium hydroxide to vaginal fluid (positive ‘whiff test’) and the presence of clue cells in microscopy of wet preparation (20). When each test (Nugent scoring system with Amsel criteria) was positive for either the presence of fungus, trichomonas vaginalis or bacterial vaginosis, the diagnosis of BV was confirmed. Aerobic vaginitis (AV) diagnosis The presence of AV was determined using an ‘AV’ score (21). The score was calculated using high-power field light microscopy (magnification, x1,000) to assess the presence or absence of healthy lactobacilli, the number of leukocytes, the number of leukocytes with toxic granulation, the type of vaginal flora and the number of parabasal epithelial cells. An ‘AV’ score of 6 to severe AV. Candidiasis was diagnosed in symptomatic patients when yeast culture in modified Stuart's medium and plated on Sabouraud dextrose agar was positive for any Candida species and no other pathogen was detected. Ureaplasma urealyticum and Mycoplasma hominis detection Ureaplasma urealyticum and Mycoplasma hominis were detected using the Mycoplasma IST2 kit (BioMerieux). The kit contained strips that provide information on the presence or absence of Ureaplasma urealyticum and Mycoplasma hominis, and also provides additional information on susceptibility to different antibiotics. Samples were vortexed rapidly at 3,500 rpm at 25˚C for 1 min and they were used (in their liquid form) to rehydrate the lyophilized growth medium provided in the kit. The Mycoplasma strips were then inoculated with 100 µl of the rehydrated growth medium overlaid with two drops of oil, then incubated at 37˚C and observed for colour changes. The results were interpreted following 24 and 48 h of incubation at 37˚C according to the manufacturer's protocol. Samples with titres ≥104 CCU/ml were considered positive. Finally, Chlamydia trachomatis was detected using the COBAS AMPLICOR test kit (cat. no. 04341341 190; Roche Diagnostics, Indianapolis, IN, USA). Human papilloma virus (HPV), cytomegalovirus (CMV), Toxoplasma, Rubella, HIV, Hepatitis B virus and Hepatitis C virus (HCV) detection HPV was detected using the LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics). This method detects 21 HPV genotypes of high risk (including 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73 and 82) and 16 HPV genotypes of low risk (6, 11, 40, 42, 54, 55, 61, 62, 64, 71, 72, 81, 83, 84, IS39 and CP6108) in cervical cells from each group preserved in PreservCyt® solution, (ThinPrep® PreservCyt® Solution; Hologic, Inc., Marlborough, MA, USA) according to the manufacturer's protocol. Additionally, anti-CMV, anti-Toxoplasma gondii and anti-Rubella IgG and IgM antibodies were measured in serum using a chemiluminescent microparticle immunoassay (Architect i-1000SR; Abbott Pharmaceutical Co., Ltd.). For the diagnosis of HIV-1/HIV-2 infection, the Architect HIV Ag/Ab Combo assay, a chemiluminescent microparticle immunoassay was utilized (Abbott Pharmaceutical Co., Ltd.). Additionally, serum Hepatitis B surface antigen, anti-HBV and anti-HCV titers were determined via an enzyme immunoassay using the ARCHITECT platform (Abbott Pharmaceutical Co., Ltd.) according to the manufacturer's protocol. Statistical analysis The incidence of demographics and symptoms were reported in all study groups (group A vs. group B) and subgroups of women receiving IVF (group C vs. group D). The type and number of symptoms as well as the type and number of pathogens were compared among all groups. To compare nominal data between two groups, the Chi-Square or Fisher test were utilized, while for all data expressed in numeric format, a Student's t-test was used. P<0.05 was considered to indicate a statistically significant difference. All P-values were calculated based on absolute values. Subgroup analysis was performed to determine potential predictors of fertility or IVF success. Furthermore to exclude any confounding factors and calculate the relative risk (RR) for the two groups, multivariate analysis using logistic regression was used. All statistical analyses were performed using IBM SPSS v.24 software (IBM Corp., Armonk, NY, USA). Ethical approval Finally, the protocol for this research project was approved by a suitably constituted Ethics Committee of Aretaieion Hospital within which the work was undertaken and it conforms to the provisions of the Declaration of Helsinki (as revised in Tokyo 2004). Results Study group characteristics A total of 215 females undergoing prenatal cervical/vaginal fluid testing in Aretaieion hospital (within a period of 5 years) were included in the current study. These comprised 111 infertile females (Group A) scheduled for IVF and 104 fertile females (Group B). The mean age of patients did not differ significantly between the two groups, although a greater number of females from Group A were >30 years of age compared with Group B (P=0.0064). Additionally, fertile females had a mean number of 1.23 children. Group A had a higher education level compared with Group B (P=0.0001), as well as a higher smoking prevalence (P=0.007). However, no significant differences in symptoms were observed between groups. In Group A, only BV (P=0.0013) was significantly more prevalent. Furthermore, infertile females possessed >2 pathogens more frequently when compared with fertile females (P=0.006; Table I). Table I. Demographics and type of pathogen present in fertile and infertile female patients. Table I. Demographics and type of pathogen present in fertile and infertile female patients. Parameter Overall (n=215) Fertile (n=104) Infertile (n=111) P-value Age (years) 31.17 30.32 31.98 NS Age ≤30 years 105 61 44 0.006 Number of children per female 0.56 1.23 0 <0.0001 Higher education 69 11 58 0.0001 Smoking 76 27 49 0.007 Symptomatic of urinary-tract infection 66 29 37 NS Symptoms Irregular discharge 66 29 37 NS Dysuria 5 2 3 NS Dyspareunia 9 7 2 NS Pruritus 32 16 16 NS Pain 15 5 10 NS Type of infection Genital mycoplasmas 32 11 21 NS Aerobic vaginitis 22 8 14 NS Bacterial vaginosis 59 18 41 0.001 Candida species 13 5 8 NS CMV 20 12 8 NS HPV 41 22 19 NS HCV 0 0 0 NS HIV 0 0 0 NS HBV 55 23 32 NS Toxoplasma 55 26 29 NS Rubella 184 88 96 NS Chlamydia trachomatis 16 7 9 NS Decreased Lactobacillus species 179 79 100 0.006 1 pathogen 34 9 25 0.008 2 pathogens 1 0 1 NS >2 pathogens 35 25 10 0.003 [i] NS, not significant; CMV, cytomegalovirus; HPV, human papilloma virus; HCV, hepatitis C; HIV, human immunodeficiency virus; HBV, hepatitis B virus; higher education, college education. Pregnancy outcome Of the 111 infertile females enrolled in the IVF program, 32 had a successful pregnancy (Group C) and the remaining 79 patients did not (Group D). The mean E2 levels for all patients undergoing IVF was 2234.38±1614.06 pg/ml, with E2 levels being higher in Group C compared with Group D (2853.75±1393.58 vs. 1983.49±1619.40 pg/ml; P=0.007). Furthermore, the number of fertilized oocytes (P=0.002) and the number of resulting embryos (P=0.004) was higher in Group C compared with group D. Male factor was more prevalent in Group C (P=0.0009) while tubal factor was more prevalent in Group D (P=0.028). Other factors, including endometriosis or ovulation disorder, did not significantly differ between the two groups. Of the pathogens examined in the current study, only Mycoplasma was detected more frequently in Group D (P=0.03; Table II). Table II. Characteristics and type of infection present in females undergoing in vitro fertilization. Table II. Characteristics and type of infection present in females undergoing in vitro fertilization. Factor Overall (n=111) Pregnant (n=32) Non-pregnant (n=79) P-value Estradiol-2 levels (pg/ml) 2234.38±1614.06 2853.75±1393.58 1983.49±1619.4 0.007 Retrieved oocytes (mean) 4.9 6.13 6.3 NS Fertilized oocytes (mean) 4.26 5.31 4.41 0.002 Embryos (mean) 2.56 2.63 3.84 0.004 Transferred embryos (mean) 2.26 2.63 2.22 0.008 Male factor infertility (n) 17 11 6 NS Tubal factor infertility (n) 39 6 6 0.0009 Endometriosis (n) 9 2 33 0.028 Ovulation disorder (n) 12 4 7 NS Unexplained infertility (n) 34 9 8 NS Vaginal discharge samples 1 pathogen 1 0 25 NS 2 pathogens 10 4 1 NS >2 pathogens 100 28 6 NS Mycoplasma species 21 2 72 NS Aerobic vaginitis 14 4 19 0.03 Bacterial vaginosis 41 10 10 NS Candida species 8 4 31 NS CMV 8 3 4 NS HPV 19 8 5 NS HCV 0 0 11 NS HIV 0 0 0 NS HBV 0 0 0 NS Toxoplasma 29 10 0 NS Rubella 96 27 19 NS Chlamydia trachomatis 9 3 69 NS [i] NS, not significant; CMV, cytomegalovirus; HPV, human papilloma virus; HCV, hepatitis C; HIV, human immunodeficiency virus; HBV, hepatitis B virus. Multivariate analysis The results of multivariate analysis revealed that a higher education [relative risk(RR)=2.31; 95% confidence interval (CI), 1.825-2.939; P30 years, smoking, the presence of decreased lactobacillus species, the presence of >2 pathogens and the presence of BV (Table III). Furthermore, tubal factor (RR=1.32; 95% CI, 1.064-1.649; P=0.012), E2 levels <2,500 pg/ml (RR=1.78; 95% CI, 1.265-2.501; P=0.0009) and Mycoplasma infection (RR=1.36; 95% CI, 1.110-1.660; P=0.003) were determined to be the strongest predictors for IVF failure (Table III). Table III. Multiregression analysis for potential risk factors associated with infertility or in vitro fertilization failure. Table III. Multiregression analysis for potential risk factors associated with infertility or in vitro fertilization failure. Risk factors Relative risk (95% CI) P-value Infertility Age >30 years 1.45 (1.109-1.905) 0.007 Higher education 2.31 (1.825-2.939) <0.0001 Smoking 1.45 (1.127-1.855) 0.004 Decreased Lactobacillus species 1.55 (1.201-1.994) 0.0007 >2 pathogens 1.83 (1.099-2.043) 0.02 Bacterial vaginosis 1.55 (1.215-1.974) 0.0004 IVF failure Tubal factor 1.32 (1.064-1.649) 0.012 Estradiol-2 levels <4,000 pg/ml 1.48 (0.868-2.539) NS Estradiol-2 levels <3,000 pg/ml 1.49 (1.007-2.213) 0.046 Estradiol-2 levels <2,500 pg/ml 1.78 (1.265-2.501) 0.0009 >2 pathogens 1.13 (0.712-1.798) NS Genital mycoplasmas 1.36 (1.110-1.660) 0.003 [i] Odds ratio and 95% confidence intervals were evaluated. The statistical significance level was defined as P<0.05. NS, not significant; higher education, college education; CI, confidence interval. Discussion The current study determined that infertility was associated with specific epidemiologic factors and certain genital tract pathogens in Greek females of reproductive age. IVF failure in infertile females was also associated with tubal factor infertility and the presence of Mycoplasma species in their genital tract. Furthermore, increased age and a higher level of education were also associated with increased infertility in the current study. This is congruent with the results of previous studies, which have reported lower fertility rates in older females (22,23). This may be due to females going to college or university and pursuing a professional career, thus becoming pregnant at an older age where oocyte number and quality has decreased, which is particularly evident after reaching the mid 30s (24). Despite the fact that higher education is associated with higher age, they were examined independently as predisposing factors of infertility in the logistic regression analysis model of the current study, which may require further investigation. Furthermore, the instance of higher education may be attributed to infertility by mechanisms other than age alone, including (25) i) less interest in having large families so that they may provide better for fewer children; ii) the better health status of educated women and of their children result in the higher survival rate of children and a reduction of the need for more children; iii) educated women are using contraceptives more often. In the current study, smoking was revealed to decrease fertility. It has been indicated that >30% of females at reproductive age are smokers (26). In an older meta-analysis, Augood et al (27) determined that women who smoked had a significantly higher odds ratio of infertility (OR 1.60; 95% CI, 1.34-1.91), in comparison to non-smokers. In addition, previous studies have indicated that low ovarian reserves, low hormone levels and tubal dysfunction may be possible mechanisms by which smoking affects fertility rate in females (28-30). Certain factors including BV and the presence of >2 pathogens were associated with low fertility in the present study. A previous study has demonstrated that BV is associated with pelvic inflammatory disease, preterm birth and infertility (31). Particularly in the case of a combined infection, the burden of pathogens could easily cause an imbalance in the cervical/uterine microbiome or dysbiosis predisposing to cervical disease or even infertility, according to a previous study (32). Although the current study did not detect an association between infertility and other pathogens, previous studies have identified a strong association of Mycoplasma and chlamydia co-infection with infertility (33,34). Finally, the current study identified that a decreased concentration of Lactobacillus species (AV score, <3) was associated with low fertility. This concurs with a previous study, where a significantly lower Lactobacilli concentration was identified in patients with BV (35). The protective potential of lactobacilli is based on their ability to regulate normal pH and inhibit the growth of vaginal microorganisms known to cause infection and adverse effects (36). A previous study has indicated that a non-Lactobacillus-dominated microbiota is associated with a significant decrease in endometrial receptivity and pregnancy rates (37). The current study also identified that tubal factor, low E2 levels and the presence of Mycoplasma were strongly associated with IVF failure. In a previous study by Kawwass et al (38), tubal factor infertility was associated with a higher miscarriage rate, preterm birth and a low birth weight risk compared with male factor infertility. Additionally, low E2 levels on the day of hCG administration have also been associated with adverse IVF outcomes (39). Joo et al (40) reported an E2 concentration-dependant effect on IVF outcomes, concluding that the optimal range of serum E2 levels in women is age-dependent: 3,000-4,000 pg/ml for women <38 years and 2,000-3,000 pg/ml for women ≥38 years. However, a meta-analysis has revealed that only female age, duration of subfertility, basal FSH levels and the number of oocytes are predictors of pregnancy following IVF (41). Considering the effect of genital tract pathogens on IVF outcomes, co-infection or infection due to genital Mycoplasmas were associated with IVF failure in the current study. Although different viruses have been previously associated with IVF failure (42,43), no such association was identified in the cohort of the present study. This may be due to the increased administration of the HPV vaccination in Greece during the recent years (44). Furthermore, Mycoplasma infections and co-infections have been strongly associated with infertility in the general population, although data specifically on patients undergoing IVF remains limited (45). Therefore, to the best of our knowledge, this is one of the first studies to assess the associations of several pathogens with IVF failure. Most presented evidence in previous literature regarding infertility in such patients is indirect, with Mycoplasma infections causing the production of several pro-inflammatory cytokines (including interleukin-1, 12 and 18, tumor necrosis factor-α and interferon-γ), which may provide a mechanistic connection between inflammatory stimulus and in vivo fertilization or embryonic growth following IVF (46). In conclusion, the current study identified a positive association between BV and infertility in a large-scale cohort of reproductive-age Greek females as well as a strong association between genital Mycoplasmas and IVF failure. Additionally, other predicting factors were determined to be associated with a negative IVF outcome. These results may result in improved management strategies for such patients to reduce infertility and failure rates in patients undergoing IVF. However, further studies with a larger number of participants and more specific criteria may be required to support the present findings, the outcome of which may improve IVF. Acknowledgements The authors would like to thank all study participants. The authors would also like to thank Aretaieion hospital, from the University of Athens for providing use of their laboratory. Funding No funding was received. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors' contributions DM developed, planned and supervised the project, and wrote the manuscript. GD performed data entry and evaluation and wrote the manuscript. SB developed and supervised the current study and wrote the manuscript. PA, RK, EK, IP, PP, AK and NA collected relevant literature. AP performed the whole statistical analysis. All authors read and approved the final manuscript. Ethics approval and consent to participate The current study was approved by the Medical Ethics Committee of Aretaieion Hospital, University of Athens (Greece). All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, and later versions. Informed consent or substitute for it was obtained from all patients prior to enrolment. Patient consent for publication All patients participating in the present study were informed in detail and agreed to the publication of associated data (and any accompanying images) as appropriate, fully respecting their anonymity and medical ethics. 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      What are the complications of genital tract infection? ›

      PID increases the risk of tubal infertility, ectopic pregnancy, and chronic abdominal pain. Tubal infertility Associated with PID and results from inflammation and scarring of the fallopian tubes following ascent of gonorrhoea, chlamydia, and possibly bacterial vaginosis organisms into the upper reproductive tract.

      What infection can cause infertility? ›

      Chlamydia and gonorrhea are important preventable causes of pelvic inflammatory disease (PID) and infertility. Untreated, about 10-15% of women with chlamydia will develop PID. Chlamydia can also cause fallopian tube infection without any symptoms.

      Does UTI infection cause infertility? ›

      UTI alone does not cause infertility among women. PID due to recurrent urinary tract infection can hamper conception chances. In many cases, diabetes can also cause frequent UTIs and affect the chances of conceiving. Even in men, UTI can cause infertility.

      What is infection of female genital tract? ›

      Female genital tract infections involving anaerobes are polymicrobial and include: soft-tissue, and perineal; bacterial vaginosis; vulvar and Bartholin gland abscesses; endometritis; pyometra; salpingitis; tubo-ovarian abscesses; adnexal abscess; pelvic inflammatory disease, which may include pelvic cellulitis and ...

      What is a common cause of genital infection? ›

      The fungus candida albicans is responsible for most vaginal yeast infections. Your vagina naturally contains a balanced mix of yeast, including candida, and bacteria. Certain bacteria (lactobacillus) act to prevent an overgrowth of yeast.

      What are the three types of reproductive tract infections? ›

      Reproductive tract infections (RTIs) include endogenous infections, iatrogenic infections and sexually transmitted infections (STIs).

      What are the top 3 causes for infertility? ›

      They include:
      • Age. Women's fertility gradually declines with age, especially in the mid-30s, and it drops rapidly after age 37. ...
      • Tobacco use. Smoking tobacco or marijuana by either partner may reduce the likelihood of pregnancy. ...
      • Alcohol use. ...
      • Being overweight. ...
      • Being underweight. ...
      • Exercise issues.
      Sep 1, 2021

      What are 4 causes for female infertility? ›

      Infertility means not being able to get pregnant after at least one year of trying (or 6 months if the woman is over age 35). If a woman keeps having miscarriages, it is also called infertility. Female infertility can result from age, physical problems, hormone problems, and lifestyle or environmental factors.

      Can an infection make it hard to get pregnant? ›

      Bacterial infections are one of the most common causes of infertility in both men and women. Sexually transmitted infections (STIs) like chlamydia and gonorrhea can damage the uterus, ovaries, and fallopian tubes in women, and the tubes that sperm travel through in men. Sometimes these infections don't cause symptoms.

      Can a UTI affect your ovaries? ›

      If left untreated, a bladder infection can worsen and travel into your uterus or ovaries, causing pelvic inflammatory disease. If you are experiencing pain while urinating, your gynecologist will most likely test your urine for infection.

      What is the leading cause of female infertility? ›

      Polycystic ovary syndrome (PCOS).

      PCOS is associated with insulin resistance and obesity, abnormal hair growth on the face or body, and acne. It's the most common cause of female infertility.

      Can bacterial vaginosis cause infertility? ›

      Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including infertility.

      What are the symptoms of genital tract infection? ›

      • vaginal itching and burning.
      • vaginal soreness and discomfort.
      • inflamed, flushed, or swollen skin around your vagina and vulva.
      • a change in the amount of vaginal discharge.
      • a change in the color of vaginal discharge.
      • pain or burning during urination.
      • pain during penetrative vaginal sex.
      • vaginal bleeding or spotting.
      Sep 5, 2019

      How is a genital tract infection diagnosed? ›

      Tests in men are performed on urine or urethral samples. Tests in women are performed on urine, cervical, or vaginal samples, which are either clinician- or self-collected. Untreated or inadequately treated patients are at increased risk for ascending infection and further complications.

      Is a yeast infection a genital tract infection? ›

      A yeast infection isn't a sexually transmitted infection (STI). Other names for a vaginal yeast infection include vulvovaginal candidiasis or vaginal candidiasis. A vaginal yeast infection is a type of vaginitis, a condition where the vagina is swollen, painful and possibly infected.

      What are the 3 most common Signs of STD infection? ›

      an unusual discharge from the vagina, penis or anus. pain when peeing. lumps or skin growths around the genitals or bottom (anus)

      What are the five signs of an infection? ›

      Know the Signs and Symptoms of Infection
      • Fever (this is sometimes the only sign of an infection).
      • Chills and sweats.
      • Change in cough or a new cough.
      • Sore throat or new mouth sore.
      • Shortness of breath.
      • Nasal congestion.
      • Stiff neck.
      • Burning or pain with urination.

      What is the best treatment for genital infection? ›

      For mild to moderate symptoms and infrequent episodes, your doctor might recommend:
      • Short-course vaginal therapy. Taking an antifungal medication for three to seven days will usually clear a yeast infection. ...
      • Single-dose oral medication. Your doctor might prescribe a one-time, single oral dose of fluconazole (Diflucan).
      Jan 11, 2023

      What causes infection in female reproductive system? ›

      Pelvic inflammatory disease (PID) is an infection of the female reproductive organs. It most often occurs when sexually transmitted bacteria spread from your vagina to your uterus, fallopian tubes or ovaries.

      Which of the following is the most common infection of the reproductive tract *? ›

      Urinary infections are the commonest type of bacterial infection that causes women to seek medical care.

      What are three 3 common signs or symptoms of female reproductive disorders and diseases? ›

      Four Signs of Reproductive Disorders in Women
      • Is This a Serious Symptom? If you feel like you're having fertility problems, you certainly aren't alone. ...
      • Not Getting Pregnant is a Sign in Itself. ...
      • Infrequent or Prolonged Menstrual Periods. ...
      • Painful Menstrual Periods or Intercourse. ...
      • Obesity, Excess Hair Growth, and Acne.
      Oct 17, 2014

      Does masturbation cause low sperm count? ›

      Frequent male masturbation isn't likely to have much effect on your fertility. Some data shows that optimum semen quality occurs after two to three days of no ejaculation. But other research suggests that men who have normal sperm quality maintain normal sperm motility and concentrations even with daily ejaculation.

      Does female masturabation cause infertility? ›

      Masturbating doesn't affect your fertility at all. There are many myths about infertility. Some people believe that masturbation can cause infertility. However, no matter your genitals, gender, or age, masturbation can't affect your ability to become pregnant or carry a pregnancy to term.

      What age is the best to get pregnant? ›

      Experts say the best time to get pregnant is between your late 20s and early 30s. This age range is associated with the best outcomes for both you and your baby. One study pinpointed the ideal age to give birth to a first child as 30.5. Your age is just one factor that should go into your decision to get pregnant.

      What are the five main factors affecting fertility? ›

      Factors Affecting Fertility
      • Age.
      • Previous Pregnancy.
      • Duration of subfertility.
      • Timing and Frequency of Sexual Intercourse.
      • Lifestyle Factors.
      • Weight.
      • Smoking.
      • Caffeine.

      What are 3 problems that can cause infertility in females? ›

      Infertility in women
      • polycystic ovary syndrome (PCOS)
      • thyroid problems – both an overactive thyroid gland and an underactive thyroid gland can prevent ovulation.
      • premature ovarian failure – where the ovaries stop working before the age of 40.

      What is it called when a man can't have babies? ›

      Male infertility means a man is not able to start a pregnancy with his female partner. Male infertility can have many causes. You may not make enough sperm or healthy sperm. You may have a genetic problem like cystic fibrosis. You may have a blockage in your genital tract.

      What infection causes delay in pregnancy? ›

      Bacterial Vaginosis and Miscarriage

      Some studies indicate a link between BV and preterm labor or miscarriage, and if the infection is really nasty and not treated, it can progress to become pelvic inflammatory disease, which can cause infertility.

      What to avoid when trying to get pregnant? ›

      Here's what to avoid when you're trying to get pregnant.
      • Smoking. ...
      • Excessive Caffeine. ...
      • Too Much Alcohol. ...
      • Being a Couch Potato. ...
      • Extreme Exercise. ...
      • Junk Food. ...
      • Chronic Stress. ...
      • High-Mercury Fish.

      Can bacterial infection prevent you from getting pregnant? ›

      There is no indication that BV affects a woman's ability to get pregnant. However, BV is associated with certain risks to the fetus, including delivering an infant preterm (before 37 weeks of pregnancy) and delivering an infant with a low birth weight (generally, 5.5 pounds or less).

      Can urinary tract infection affect uterus? ›

      Urinary tract infections can affect any part of the urinary tract, including the kidney, ureter, bladder, urethra, and the uterus. The common infections affect urethra and bladder; however, a more serious infection can occur in the kidneys or uterus.

      Can urinary tract infection affect the womb? ›

      * UTI and infertility

      If the infection persists or recurs frequently, especially affecting the upper tract (kidney, uterus, fallopian tubes), it might affect your ability to conceive. This condition is also called as pelvic inflammatory disease which can damage the fallopian tubes severely.

      Can ovarian infection cause infertility? ›

      Although they may require treatment, they don't affect fertility.

      Can a woman get pregnant if she's on top of the man? ›

      No matter whether you're doing it in the missionary position, woman-on-top, doggie style, spooning, or standing up, a woman has an equal chance of getting pregnant during unprotected sexual intercourse. The idea that woman-on-top leads to lower chances of conception is a misconception, a myth, and misinformation.

      How do I make sure I have a girl? ›

      There's only one guaranteed way to conceive a girl, which is a procedure known as sex selection. This in vitro fertilization method (IVF) involves implanting a girl or boy embryo into the mother's uterus. This option, however, is expensive, and even illegal in some countries.

      How can you tell if a woman is infertile? ›

      Signs of Potential Infertility in Women
      1. Abnormal periods. Bleeding is heavier or lighter than usual.
      2. Irregular periods. The number of days in between each period varies each month.
      3. No periods. You have never had a period, or periods suddenly stop.
      4. Painful periods. Back pain, pelvic pain, and cramping may happen.
      Oct 1, 2021

      What are the chances of BV causing infertility? ›

      BV is not associated with decreased conception rates (OR 1.03, 95% CI 0.79-1.33). Similarly, none of the studies found an association between abnormal vaginal flora and conception rates following IVF treatment.

      Is bacterial vaginosis an STD? ›

      Bacterial vaginosis (BV) is a common cause of unusual vaginal discharge. BV is not a sexually transmitted infection (STI), but it can increase your risk of getting an STI such as chlamydia.

      What happens if bacterial vaginosis goes untreated? ›

      Most often, BV does not cause other health problems. However, if left untreated, BV may increase your risk for: Sexually transmitted diseases (STDs) like herpes, chlamydia, gonorrhea, and HIV. Pelvic inflammatory disease where BV bacteria infect the uterus or fallopian tubes.

      What is female genital tract disorder? ›

      Some examples of female genital disorders include cancer, Chlamydia, herpes and candidiasis. pelvic pain, genital pain, vaginal bleeding, vaginal itching can be considered as the symptoms of female genital disorders. The main symptom among these is vaginal discharge which refers to secretions from vagina.

      Can infections cause infertility? ›

      PID and “silent” infection in the upper genital tract may cause permanent damage to the fallopian tubes, uterus, and surrounding tissues, which can lead to infertility.

      How do you get a genital bacterial infection? ›

      However, we do know the condition most often occurs in those who are sexually active. BV is a result of an imbalance of “good” and “harmful” bacteria in a vagina. Douching, not using condoms, and having new or multiple sex partners can upset the normal balance of vaginal bacteria, increasing your risk for getting BV.

      How can you prevent genital tract infections? ›

      STI prevention means reducing exposure—by using condoms and reducing numbers of sex partners. Condoms must be used correctly and consistently to prevent STI. Adolescents should receive support for decisions to delay sexual activity. The risk of iatrogenic infection can be reduced by good infection control procedures.

      How do you know you have a yeast infection and not a STD? ›

      Ultimately, you can't know for sure if you have a yeast infection or an STD unless you get tested by a doctor. You'll want to set up an appointment as soon as possible if you have any of the following symptoms: Vaginal or vulvar itching, soreness, and irritation. A burning feeling during sex or urination.

      Which infection is known for causing genital yeast infections? ›

      Candida can cause an infection if conditions change inside the vagina to encourage its growth. Things like hormones, medicines, or changes in the immune system can make infection more likely. The common term for candidiasis in the vagina is a vaginal yeast infection.

      Can genital yeast infection be cured? ›

      Yeast infections can usually be cured easily in a few days with anti-fungal medicine. You can get medicated creams or suppositories for yeast infections (like Monistat and other brands) at a drugstore, over-the-counter without a prescription.

      What are signs of complications of the infection? ›

      What are the signs and symptoms that an infection has become worse?
      • Fever or very low body temperature with chills and violent shaking.
      • Swelling in the ankles or legs.
      • A change in mental status such as confusion, loss of consciousness, or seizures.
      • A fast or irregular heartbeat.
      • Urinating very little or not at all.

      What are the complications from a bacterial STD? ›

      Some of the health complications that arise from STDs include pelvic inflammatory disease, infertility, tubal or ectopic pregnancy, cervical cancer, and perinatal or congenital infections in infants born to infected mothers.

      What are some major complications of getting an STD? ›

      • Pelvic pain.
      • Pregnancy complications.
      • Eye inflammation.
      • Arthritis.
      • Pelvic inflammatory disease.
      • Infertility.
      • Heart disease.
      • Certain cancers, such as HPV -associated cervical and rectal cancers.
      Sep 21, 2021

      What are 2 serious signs of infection? ›

      Know the Signs and Symptoms of Infection
      • Fever (this is sometimes the only sign of an infection).
      • Chills and sweats.
      • Change in cough or a new cough.
      • Sore throat or new mouth sore.
      • Shortness of breath.
      • Nasal congestion.
      • Stiff neck.
      • Burning or pain with urination.

      What happens if you have an infection for too long? ›

      If you don't stop that infection, it can cause sepsis. Bacterial infections cause most cases of sepsis. Sepsis can also be a result of other infections, including viral infections, such as COVID-19 or influenza, or fungal infections.

      What are 5 common symptoms of a bacterial infection? ›

      What are the symptoms of a bacterial infection?
      • fever.
      • feeling tired or fatigued.
      • swollen lymph nodes in the neck, armpits, groin or elsewhere.
      • headache.
      • nausea or vomiting.

      What tests are done for genital tract infection? ›

      Tests in men are performed on urine or urethral samples. Tests in women are performed on urine, cervical, or vaginal samples, which are either clinician- or self-collected. Untreated or inadequately treated patients are at increased risk for ascending infection and further complications.

      What will be the result of infections in STDs develop and left untreated? ›

      Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) as they are also referred to, often have no symptoms. However, if left untreated there can be serious consequences including blindness and other neurologic manifestations, infertility, mother-to-child transmission or birth defects.

      What is the most damaging STD? ›

      The most dangerous viral STD is human immunodeficiency virus (HIV), which leads to AIDS. Other incurable viral STDs include human papilloma virus (HPV), hepatitis B and genital herpes.


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