# The Role of the Cervix in Fertility: Is It Time for a Reappraisal? Martyn, F., McAuliffe, F.M., Wingfield, M., 2014. The role of the cervix in fertility: is it time for a reappraisal? Human Reproduction 29, 2092–2098. [LINK](https://doi.org/10.1093/humrep/deu195) >[!Abstract] > Knowledge regarding the role of the cervix in fertility has expanded considerably over the past 20 years and in this article, we propose that it is now time for its function to be reappraised. First, we review the anatomy of the cervix and the vaginal ecosystem that it inhabits. Then, we examine the physiology and the role of the cervical mucus. The ongoing mystery of the exact mechanism of the sperm–cervical mucus interaction is reviewed and the key players that may unlock this mystery in the future are discussed. The soluble and cellular biomarkers of the lower female genital tract which are slowly being defined by contemporary research are reviewed. Attempts to standardize these markers, in this milieu, are hindered by the changes that may be attributed to endogenous or exogenous factors such as: age, hormonal changes during the menstrual cycle, ectropion, infection, smoking and exposure to semen during sexual intercourse. We review what is known about the immunology of the cervix. With the widespread use of large loop excision of the transformation zone (LLETZ) for treatment of cervical intraepithelial neoplasia, the anatomy of the cervix is changing for many women. While LLETZ surgery has had very positive effects in the fight against cervical cancer, we debate the impact it could have on a woman's fertility. ## Notes - monitoring your cervix - cervix anatomy - the cervix acts as a barrier - the cervix is the door to the female reproductive system - the vagina has a low ph and is toxic to both bacteria and sperm - cervical mucus is considerably less acidic than the vagina %% [Open in Zotero](zotero://select/items/@Martyn2014) [[(Martyn et al, 2014) The role of the cervix in fertility.pdf]] #### [Page 1](highlights://(Martyn%20et%20al,%202014)%20The%20role%20of%20the%20cervix%20in%20fertility#page=1) ## **Introduction** ### [[the cervix acts as a barrier]] > The cervix plays a fascinating gatekeeping role in first, preventing the ascent of pathogens from the vagina into the uterus, and second, allowing the ascent of sperm to the Fallopian tubes. It is also crucial for the maintenance of pregnancy in the uterus until the onset of labour ^bh175 ## **Anatomy and physiology of the cervix** ### [[cervix anatomy]] > The cervix is made up of the ectocervix and endocervix and is on average 3 – 4 cm long and 2.5 cm wide (Pardo et al., 2003; Mazouni et al., 2005; Robert et al., 2013). The ectocervix is the portion of the cervix projecting into the vagina. ^irhsy > The opening of the ectocervix to the vagina is called the external os. Although studies of cervical length in non-pregnant women are few, it is acknowledged that the size and shape of both the cervix and the external os differ in women (Pardo et al., 2003; Mazouni et al., 2005) and vary with age, hormonal changes, parity and surgical treatments to the cervix. ^kmlw3 ## **Cervical and vaginal ecosystem** ### [[The vagina has a low pH and is toxic to both bacteria and sperm]] > The vaginal pH is kept between 3.8 and 4.5 by the anaerobic metabolism of vaginal glycogen to acidic products, predominantly acetic and lactic acid (Boskey et al., 1999) and this low pH is toxic to both bacteria and sperm. The vagina is colonized by a large quantity of micro-organisms with the Lactobacillus spp. predominating. It is thought that it is the ability of the lactobacilli to produce hydrogen peroxide, which can combine with chloride in the vagina, that produces this acidic antimicrobial defence (Klebanoff et al., 1991). ^comhy > It is believed that most women have a homogenous vaginal flora with only one lactobacillus species (Vasquez et al., 2002) and these gram-positive, non-motile rod-like lactobacilli are able to tol- erate and grow in these acid conditions (Wilks et al., 2004). The most common species found in the female vagina are Lactobacillus gasseri, L. crispatus, L. vaginalis, L. jensenii, L. iners and Latobacillus sp. 1086V. These lactobacilli form an important non-specific antimicrobial host defence which, combined with the vagina’s low pH, protects the lower female genital tract from ascending infections (Carr et al., 1998) ### [[cervical mucus is considerably less acidic than the vagina]] > In contrast to the vagina, the pH of cervical mucus is 7.0 (Correa et al., 2001) and so is considerably less acidic. The normal pH of semen ranges from 7.2 to 8.0 (Haugen and Grotmol, 1998) and thus the cervical mucus pH supports sperm viability (Eggert-Kruse et al., 1993). ^ebfvt ## **Cervical mucus** > The cervical mucus is composed of water (95 – 99%), ions, enzymes, bactericidal proteins, plasma proteins and mucins > Our understanding of the biochemical properties of cervical mucus is still evolving > Recent studies have examined the differ- ent types of mucins and how they vary over a woman’s cycle. Up to 16 different mucins have been identified with at least five in the female repro- ductive epithelia (Andersch-Bjorkman et al., 2007). Three have been described as gel forming (MUC 5B, MUC 5AC, MUC 6) and two are membrane bound (MUC1 and MUC 16). It appears that MUC5B is the major mucin of the cervical mucus and that it has its highest expression at midcycle (Gipson et al., 1997, 2001; Flori et al., 2007). > The start of the fertile interval corresponds with a rise in estrogen levels before ovulation and an increase in the secretion of cervical mucus which is more watery (Flynn and Lynch 1976; Adamopoulos et al., 2000; Bigelow et al., 2004). This watery, estrogen effected mucus facilitates sperm migration into the uterus (Bigelow et al., 2004) > After ovulation, when, under the influence of the corpus luteum, the ovary begins to secrete progesterone, the amount of cervical mucus is reduced and it becomes thicker and stickier (Ulcova-Gallova 2010). This mucus blocks sperm migration. It is estimated that the cervix produces mucus at a rate of 20–60 mg/day and that this increases (up to 10-fold) to 700 mg/day around ovulation (Moriyama et al., 1999). These menstrual cycle changes are critical for fertility ## **Sperm – cervical mucus interactions** #### [Page 3](highlights://(Martyn%20et%20al,%202014)%20The%20role%20of%20the%20cervix%20in%20fertility#page=3) > The range of human sperm longevity is thought to vary from 24–48 h to as long as 5 days (Zinaman et al., 1989). > Sperm are not able to fertilize eggs immediately after ejacu- lation. It is known that sperm acquire fertilization capacity by residing in the female genital tract and undergoing a series of physiological changes, which are collectively known as capacitation ## **Inflammatory and immunological factors at the cervix** > The mucosal immune system of the cervix con- sists of immune cells that migrate there, as well as resident epithelial cells and supportive stromal cells (Wira et al., 2005). The epithelial cells are sentinel cells that function as part of the innate and adaptive immune system. They are responsive to hormonal changes and produce a number of soluble mediators. It is these soluble mediators that influence immune cell migration and defence against local pathogens, while also optimizing reproductive potential (Wira et al., 2010 > Given that sperm are foreign bodies in the female reproductive tract, immune mechanisms are involved in allowing these allogeneic cells to #### [Page 4](highlights://(Martyn%20et%20al,%202014)%20The%20role%20of%20the%20cervix%20in%20fertility#page=4) > remain in the female genital tract without eliciting an adverse immune re- sponse > We have already described the sialic acid rich coating on the sperm, and their corresponding receptors, Siglecs. These are thought to have an important role in protecting sperm from the female’s immune response after sexual intercourse (Crocker et al., 2007). It is thought that the sperm must properly engage with the Siglecs to prevent female immune recognition and avoid demise (Ma et al., 2012). #### [Page 5](highlights://(Martyn%20et%20al,%202014)%20The%20role%20of%20the%20cervix%20in%20fertility#page=5) ## **Conclusion** ### [[the cervix is the door to the female reproductive system]] > The cervix is the door to the female reproductive system. Anatomically, it must allow sperm passage into the uterus through the endocervical canal and it must produce mucus to facilitate sperm entry. Immunologically, it must recognize and prevent pathogen entry. ^g7dwc