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      Insights into the role of cervical mucus and vaginal pH in unexplained infertility Translated title: SOBRE O PAPEL DO MUCO CERVICAL E DO PH VAGINAL NA GÊNESE DA INFERTILIDADE INEXPLICADA

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          Abstract

          Unexplained infertility diagnosis is made in the presence of a normal semen analysis when tubal patency and normal ovulatory function are established. Among several potential causes, unexplained infertility could be attributed to vaginal pH and cervical mucus abnormalities. Although the vaginal canal and the cervix generally function as effective barriers to sperm, and although the production of mucus is essential to transport them from the vagina to the uterine cavity, these factors receive little attention in the investigation of couples with unexplained infertility. A substantial reduction in sperm number occurs as they transverse the cervix. From an average of 200 to 300 million sperm deposited in the vagina, only a few hundred achieve proximity to the oocyte. Given this expected high spermatozoa loss, a slight modification in cervical mucus may rapidly transform the cervix into a "hostile" environment, which, together with changes in vaginal environment and cervix structure, may prevent natural conception and be a cause of infertility. In this review, we discuss the physiological role of the vaginal pH and cervical mucus in fertility, and describe several conditions that can render the cervical mucus hostile to sperm and therefore be implicated in the pathophysiology of unexplained infertility.

          Translated abstract

          RESUMO O diagnóstico de infertilidade inexplicada baseia-se na presença de espermograma normal, constatadas também permeabilidade tubária e função ovulatória normais. Entre as várias causas potenciais de infertilidade inexplicada, a presença de muco cervical e pH vaginal anormais devem ser consideradas. Embora a produção adequada de muco cervical seja essencial para o transporte dos espermatozóides da vagina para a cavidade uterina, e tanto o canal vaginal quanto o colo do útero desempenham função importante como barreira à passagem dos espermatozóides, estes fatores recebem pouca atenção na investigação de casais com infertilidade inexplicada. Uma redução substancial do número de espermatozoides ocorre à medida que estes percorrem o trato reprodutivo feminino. Partindo de cerca de 200 a 300 milhões de espermatozoides depositados na vagina, apenas algumas centenas alcançam a proximidade do oócito. Alteracões do muco cervical podem rapidamente transformar o colo do útero num ambiente hostil, que em conjunto com alterações no ambiente vaginal e da estrutura de colo do útero, podem apresentar-se condicões impedientes para a concepção natural; desse modo, convertem-se em causa de infertilidade. Nesta revisão, discutimos o papel fisiológico do pH vaginal e do muco cervical na fertilidade, descrever várias condicões que podem tornar o muco cervical hostil aos espermatozoides e, por fim analisamos como estes fatores interferem na fisiopatologia da infertilidade inexplicada.

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          Most cited references182

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          Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis.

          For more than 20 years, the abnormally thick mucus (mucoviscidosis) in cystic fibrosis has been widely shown to be linked to a genetic defect in the cystic fibrosis transmembrane conductance regulator Cl(-) channel. The defect is widely thought to cause mucus to become dehydrated as a result of basic defects in Cl(-) dependent fluid transport. However, this widely held explanation is inconsistent with the known physiological properties and functions of organs affected by cystic fibrosis. During the process of releasing highly condensed mucins from intracellular granules, Ca(2+) and H(+) cations must be removed to enable the mucins to expand by as much as 1000 times, forming extracellular mucus-gel networks. Over the past few years, that HCO(3)(-) transport is also defective in patients with cystic fibrosis has become apparent. I propose that HCO(3)(-) is crucial to normal mucin expansion because it forms complexes with these cations. Thus, because HCO(3)(-) secretion is defective in cystic fibrosis, mucins in organs affected by cystic fibrosis tend to remain aggregated, poorly solubilised, and less transportable. If the hypothesis is valid, pathogenesis in cystic fibrosis could be due as much to defective transport of HCO(3)(-) as to defective Cl(-) transport.
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            Smoking and female infertility: a systematic review and meta-analysis.

            The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta-analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF-treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.
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              Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora.

              The vaginal microflora of healthy asymptomatic women consists of a wide variety (two to five isolates at any one time) of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. That the vaginal flora forms part of a dynamically changing ecosystem is evident from the variable prevalence and population levels of each bacterial species detected with repetitive longitudinal sampling, with pregnancy, and with stage in the menstrual cycle. This review emphasizes the role that vaginal lactobacilli may play in control of the vaginal microflora and maintenance of the normal state. Lactobacilli possess many antagonistic properties and produce many metabolites that may be important in maintaining dominance in the vagina. Contradictory data from previous studies regarding the impact of factors such as contraception, catamenial products, and physiologic elements on the vaginal microflora are due in part to poor study design and differences in methodology. Well-designed and controlled investigations with large numbers of individuals in each group are needed, and the limitations of the methodology for such investigations must be considered. Studies of the normal flora, exploring the interaction of lactobacilli and other bacterial species, must be performed before the pathologic processes resulting in vaginitis or systemic sequelae are investigated.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                medical
                MedicalExpress
                MedicalExpress (São Paulo, online)
                Mavera Edições Técnicas e Científicas Ltda
                2358-0429
                March 2015
                : 2
                : 2
                : M150207
                Affiliations
                [1 ] Centro de Referência para Reprodução Masculina, Brazil
                [2 ] Universidade Estadual de Campinas Brazil
                Article
                S2358-04292015000200007
                10.5935/MedicalExpress.2015.02.07
                59e4904f-a0e7-4667-b604-10889aa4dbba

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=2358-0429&lng=en
                Categories
                HEALTH CARE SCIENCES & SERVICES

                Health & Social care
                Sperm transport,Cervix mucus,Hydrogen ion concentration,Sperm agglutination,Uterine cervix disease,Vaginal disease,Female infertility,Unexplained infertility,transporte espermático,muco cervical,concentração hidrogeniônica,aglutinação espermática,moléstia cervical,moléstia vaginal,infertilidade feminina,infertilidade inexplicada

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