Cervical cerclage

Cervical cerclage is the surgical insertion of a suture (stitch) around the cervical neck (Alfirevic 2017; Yorifuji 2014) in pregnant women. The cervix is the lower part of the uterus that opens to the vagina. Cerclages are placed in pregnancy based on various indications as either an emergency technique in cases of threatened abortion (indicated by physical examination), a prearranged technique based on prior history, or due to a short cervical length identified via transvaginal ultrasound (Alfirevic 2017; Baxter 2005). History‐indicated cervical cerclage is used for those women with one or more second‐trimester losses due to documented cervical insufficiency or a history of cervical cerclage during a prior pregnancy secondary to cervical insufficiency (ACOG 2014). Ultrasound‐indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation (Barbosa 2020). Physical examination‐indicated cervical cerclage is painless cervical dilatation on sterile vaginal examination or sterile speculum examination at between 14 and 24 weeks gestation (ACOG 2014). Emergency cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length less than 20 mm in a woman with cervical dilatation (Barbosa 2020). Based on the current role of cervical cerclage in preventing preterm birth, we note that the efficacy and safety of cervical cerclage in the management of pregnancy with associated cervical insufficiency following the age of fetal viability has not been sufficiently evaluated. Cervical cerclage should be restricted to pregnancies in the second trimester prior to attainment of fetal viability.

Cervical cerclage was pioneered by VN Shirodkar (Shirodkar 1955). Shirodkar, a professor of midwifery and gynaecology in Grand Medical College in Bombay, India, developed cervical cerclage based on his discovery that some pregnant women have repeated pregnancy losses from the fourth to the seventh months of pregnancy, which are not mitigated by bed rest or treatment with hormonal therapy (Shirodkar 1955). Two years after Shirodkar's discovery of cerclage, Ian McDonald, based at the Royal Melbourne Hospital, Australia, shared his knowledge involving 70 women who had cervical suture placement for inevitable abortion (McDonald 1957). A randomised controlled study of women with short cervical length and receiving cervical cerclage revealed that there was no significant dissimilarity in the prevention of preterm birth when the two methods were compared (Odibo 2007). The methods of cervical cerclage have subsequently undergone several modifications, ranging from the type of suture material to the technique and timing of the insertion of sutures (Smith 2009). Anaesthesia and theatre are needed for insertion of a cervical cerclage and this could be linked with various forms of complications. For example, the published adverse events immediately following cervical cerclage placement include traumatic rupture of membranes (0.4%), vaginal bleeding (1.4%), and premature rupture of fetal membranes (15.6%) (Azem 2004; Rush 1984; Simcox 2007). A previous systematic review has reported a 2½‐fold increased risk of chorioamnionitis (Alfirevic 2017). Other complications include suture detachment (1.4%) (Azem 2004), preterm delivery (16.4%) (Azem 2004), cervical lacerations (8.9% to 25.0%) (Jongen 1997; Simonazzi 2015), cervical dystocia (7.2%) (Azem 2004), uterine rupture (6.3%) (Jongen 1997), and postpartum haemorrhage (2.8%) (Azem 2004). There was no statistically significant decline in the incidence of cervical lacerations between the women who had cervical cerclage removal planned before labour and those removed post‐labour onset (Simonazzi 2015). A 1% incidence of difficulty in cerclage removal has also been reported (MRC/RCOG 1993). General anaesthesia is more frequently used (82.5%) for cervical cerclage placement (Ioscovich 2015). When general anaesthesia is used, a few authorities have contended that the stress associated with endotracheal intubation may escalate the activity of uterine smooth muscles a well as stimulating spontaneous abortion, an effect cervical cerclage is intended to avert; nevertheless, the proof for this claim is conflicting (Ioscovich 2015; Yoon 2008). In addition, there are known contraindications to cervical cerclage, such as vaginal bleeding and premature rupture of membranes.

Antibiotics

Antibiotics are medicines to deal with diseases or infections caused by bacteria. The introduction of antibiotics in the 1940s and 1950s has saved millions of lives, including those of pregnant women and their fetuses and babies. During pregnancy, the prescription of antibiotics often presents a dilemma. The current concept and recommendation of ACOG is that pregnant women at risk of preterm birth should not be treated with antibiotics for the single aim of preventing spontaneous preterm birth (ACOG 2003). Studies have found that preconception use of antibiotics to treat women at elevated risk of spontaneous preterm birth is not efficacious in reducing the likelihood of delivering a preterm infant, and may occasionally lead to an elevated risk of subsequent preterm delivery (Andrews 2006; Tita 2007). However, antibiotic therapy could be life‐saving and effective in certain circumstances (Eleje 2014; Sangkomkamhang 2015). Antibiotic use causes an antibiotic‐mediated suppression of infection and preterm birth. Antibiotics can treat confirmed infection and could prevent ascending vaginal infection (Farr 2015; Sangkomkamhang 2015).

Vaginal support pessary

A vaginal support pessary is a medical device used to support the uterus, vagina, urinary bladder and rectum. The traditional role of the vaginal pessary is for conservative treatment of pelvic organ prolapse, such as cystocele (where the bladder bulges into the vagina) or rectocele (where part of the rectum bulges into the vagina) (Abdulaziz 2015). Vaginal pessaries are also useful in the treatment of stress urinary incontinence (Chughtai 2012). Their role at eliminating spontaneous preterm birth is therefore not standard. The vaginal pessary can be placed temporarily or permanently, and must be fitted by trained medical personnel. It can be worn during sexual intercourse. In Europe, some medical practitioners have used the vaginal pessary for prevention of spontaneous preterm births (Arabin 2003). According to some studies, pessary use is not a first‐line approach but should serve as a combination treatment or co‐intervention therapy following cervical cerclage procedures (Newcomer 2000; Patro‐Malysza 2009), or could be useful in women not needing cervical cerclage (Newcomer 2000). Another study concluded that vaginal pessary and cervical cerclage are correspondingly efficacious as methods of preventing spontaneous preterm births in pregnant women presenting with cervical insufficiency, and the decision to use one or the other method influences neither the route of delivery nor the outcome for the newborn (Antczak‐Judycka 2003). A recently‐published prospective randomised clinical trial (Goya 2012) involved women with an ultrasound cervical length of 25 mm or less, and a gestational age of 18 to 22 weeks, randomly assigned to either an expectant management arm or a vaginal pessary arm. The women had a short cervix rather than a prior preterm birth event. The trial concluded that, with a vaginal pessary, preterm birth could be prevented in a population with adequate participant selection of women at risk of preterm births, especially those already screened using midtrimester cervical length assessment. Randomised and non‐randomised studies have indicated the usefulness of vaginal pessaries in preventing spontaneous preterm birth (Liem 2013). The insertion and removal of the pessary is simple and usually well tolerated by the woman (Liem 2013). However, when used as a preventive tool for preterm birth, the gestational age for removal of the vaginal pessary is usually at the 37th week. The vaginal pessary is usually removed before 37 weeks of gestation when there is vaginal bleeding, persistent uterine contractions even in the presence of tocolysis, or when the pessary is causing discomfort (Goya 2012).

Reinforcing or second or repeat cerclage placement

Reinforcing a cerclage (also known as second or repeat cerclage placement) can be carried out with transvaginal ultrasonographic guidance following cervical surveillance post‐cervical cerclage, with the repeat suture insertion performed when persistent cervical effacement (thinning of the cervix) develops (Baxter 2005; Fox 1998). This second (repeat) cerclage placement is usually performed at less than 27 weeks of gestation, following report of initial cervical cerclage suture failure, especially when cervical length was subsequently found to be less than 25 mm (Althuisius 2000). During cerclage suture reinforcement or repeat cerclage placement, the cerclage already in place is not manipulated but a second cerclage is placed to reinforce the first one (Baxter 2005; Fox 1998). The reinforcement suture is therefore the second (repeat) cerclage placement (Althuisius 2000). Although the tightening can be done vaginally, cervical cerclage sutures can be tightened under transrectal or transabdominal ultrasound guidance up to the point that the cervical canal is no longer visible. Once the suture is tightened, ultrasound can also be useful in assessing both the length and width of the cervix. Nevertheless, an hourglass appearance, as seen in the cervix at ultrasonography following reinforcement of sutures, may be a risk factor for spontaneous preterm births (Hershkovitz 2008).

Tocolytics

Tocolytics (labour repressants or anticontraction medications) are medications used to suppress premature labour. Tocolytic is derived from the Greek word tokos, (meaning childbirth) and from the word lytic, (meaning potential ability to dissolve) (Tan 2006). The therapy could be useful because it gives more time for glucocorticoid therapy to be administered, which significantly speeds up fetal lung maturity (Flenady 2014).

A number of different tocolytics are in common use as combination treatments with cervical cerclage in preventing spontaneous preterm birth and preterm labour (Eke 2016; Smith 2015). The most widely used drugs include beta‐adrenoceptor agonists (e.g. ritodrine), oxytocin receptor antagonist (e.g. atosiban), prostaglandin inhibitors (indomethacin), calcium channel blockers (e.g. nifedipine), and magnesium sulphate (Van Vliet 2014; Vogel 2014). Of all the tocolytics, nifedipine, beta‐agonists, atosiban and indomethacin, but not magnesium sulphate, have proven efficacy and can be given for 48 hours postoperatively, implying also that they can be given because of their steroid benefit and in‐utero transfer benefit (Flenady 2014; Vogel 2014). Although each one is efficacious, each has an advantage over the others. Calcium channel blockers have been shown to have benefits over betamimetics for pregnancy elongation, severe morbidity in the neonates, and maternal adverse effects (Flenady 2014). Blockers of calcium channel could also have some therapeutic advantages over atosiban and magnesium sulphate, although atosiban results in rarer adverse effects for the mother (Flenady 2014). Magnesium sulphate is now only indicated for fetal neuroprotection (Crowther 2014). The ideal tocolytic drug should be effective in prolonging preterm labour and birth, and should have a favourable safety profile in both the women and their unborn babies, culminating in reductions in neonatal morbidity and mortality.

Progesterone

Progesterone is a sex steroid produced naturally in the ovary by the corpus luteum, and also in the placenta at a gestational age corresponding to the last two trimesters of pregnancy. Progesterone and its agents exist in various forms. Progestogens are agents that have progesterone‐like action (Romero 2014a), and are now the principal agent for preventing spontaneous preterm deliveries (Likis 2012). 17‐α‐hydroxyprogesterone caproate is a synthetic progestogen. The 'caproate molecule' is not made by the human body, but is produced in the laboratory when the molecule is added to 17‐α‐hydroxyprogesterone. In order to lengthen the drug's half‐life, the caproate molecule is incorporated, thereby producing some structural modification of the drug molecule and resulting in pharmacological or physiological changes in the properties of the drug. One clinical study of 17‐α‐hydroxyprogesterone revealed a reduction in the spontaneous preterm delivery rate in women with previous history of preterm deliveries (Meis 2003). Another study showed that 17‐α‐hydroxyprogesterone caproate injections reduced the likelihood of recurrent preterm births by approximately 30% (Manuck 2016). However, despite prophylactic 17‐alpha hydroxyprogesterone caproate, up to 30% of recipients will still have a recurrent preterm birth, as non‐responders to the 17‐α‐hydroxyprogesterone (Manuck 2016a). One recent study concluded that 17‐alpha hydroxyprogesterone caproate was not effective in preventing recurrent preterm birth (Nelson 2017). Although the present global protocol recommends initiation of 17‐alpha hydroxyprogesterone caproate from 16 to 20 weeks, 17‐alpha hydroxyprogesterone caproate could be started at any gestational age in clinical practice (Ning 2017).

The first well‐conducted randomised clinical study evaluating the role of vaginally‐administered progesterone in preventing spontaneous preterm birth in pregnant women with a history of short cervix was reported by Fonseca 2007. Recent studies have shown that progesterone administration by the vaginal route lowers the frequency of spontaneous birth at preterm gestation in women with a history of short cervical length, irrespective of prior histories of preterm births (Romero 2014a). However, when consideration is given to women with prior preterm births, the effectiveness of vaginal progesterone is the same as that of cervical cerclage in preventing spontaneous preterm births (Romero 2014a). Another study comparing the efficacy of 17‐OH progesterone, dydrogesterone as well as oral or vaginal micronised progesterone in combination with cervical cerclage for preventing preterm delivery in women with short cervical length, concluded that combination treatment significantly benefits pregnancy outcomes in cases of short cervical length compared with cervical cerclage, 17‐OH progesterone, dydrogesterone, or oral progesterone alone (Pustotina 2017). The safety of progesterone agents in early pregnancy is widely acknowledged; studies involving vaginal progesterone for preventing spontaneous preterm delivery have further clarified that they are safe in early pregnancy as there were no differences in adverse events between women who received progesterone and those who received inactive placebo (Slager 2012). 17‐hydroxyprogesterone caproate has also been studied in the setting of prophylactic and ultrasound‐indicated cerclages (Eke 2019a; Lichter 2019). In addition, a recent systematic review demonstrated that singleton pregnancies that were being administered with weekly doses of 17α‐hydroxyprogesterone caproate for the prevention of recurrent preterm births had an exponentially greater proportion of women with anomalous glucose test results and gestational diabetes mellitus when compared with non‐intervention groups, a result that did not apply to randomly assigned women receiving 17α‐hydroxyprogesterone caproate (Eke 2019b).

Omega‐3 long chain polyunsaturated fatty acid

Reports from some randomised studies show that supplementary therapy using omega‐3 long chain polyunsaturated fatty acid significantly lowers the frequency of "recurrent preterm birth" (Olsen 2000). Evidence from human‐ and animal‐documented reports have shown that the n‐3 as well as the n‐6 series of essential fatty acids, including their respective 'eicosanoid metabolites', are strongly implicated in the length of pregnancy and parturition (Allen 2001). Prostaglandins of the 2‐series have been shown to be involved in remodelling of parturition and connective tissue that is related to maturation of the cervix and membrane ruptures. When genital infections are absent, preterm delivery will be characterised by lower expression of prostaglandins in the tissues of the reproductive tract, with resultant lower expression of inducible cyclo‐oxygenase. Pregnant women who have had premature delivery often have high blood levels of n‐6 fatty acid but low blood levels of n‐3 fatty acids, regardless of the decreased rate of production of prostaglandin (Allen 2001). A number of studies of n‐3 fatty acid supports in pregnancy have revealed a marked decrease in the frequency of births at preterm gestations; however, there could be an increase in birthweight due to the associated prolonged length of pregnancy (Saccone 2015a). It has been recommended that docosahexaenoic acid (n‐3 fatty acids long chain molecule) as pregnancy supplementation should be used to extend the duration of pregnancy in women with high risks of spontaneous preterm births (Allen 2001).

Bed rest

The description of bed rest is two‐fold, i.e. partial, which involves bed rest for some hours (but not up to 24 hours) during the day's work, or complete, which involves strict bed rest lasting up to 24 hours a day (Smith 2009). The term 'bed rest', as defined by Fox 2009, is the "limited ambulation of not more than one to two hours per day with bathroom use and bathing permitted". Although the terms 'activity restriction' and 'bed rest' are usually used synonymously in clinical practice, the two terms vary to some extent. The term 'activity restriction' is generally preferable to 'bed rest'; some women may not be confined to bed by their obstetrics care providers but restriction could be placed on some activities such as sexual intercourse, child lifting or other maternal behaviours, without restricting maternal ambulation. It is important to note that when ambulation is allowed, the problems of bed rest are diminished in accordance with the amount of ambulation.

Restriction of activity or bed rest during the antenatal period have become the central component of treatments aimed at preventing spontaneous preterm birth. Not only have such activity restrictions been used for more than 35 years, but about one million women use the intervention each year in the United States (Maloni 2010). However, evidence is lacking that this behaviour produces the desired results (Sosa 2015). In fact, there is strong evidence that bed rest or activity restriction could cause a number of adverse psychological and physiologic side effects in mothers and their newborns (Maloni 2010; Sosa 2015), but this has not impacted positively on obstetrics practice (Maloni 2010).

Cervical cerclage

Cerclage is based on the hypothesis that some pregnant women have cervical weakness or malfunction contributing to the preterm delivery pathways (Althuisius 2003; Vidaeff 2009). It works by holding the cervical 'os' (opening) closed. The procedure for cervical cerclage is posited on the woman carrying the pregnancy until or close to 37 weeks' gestation.

Antibiotics

One mechanism by which untreated urinary tract infections and bacterial vaginosis cause preterm labour is through upward movement of the microorganisms from the areas of vagina and cervix and to the placenta, decidua and membranes' surfaces, and subsequent multiplication at these sites (Cram 2002; Eleje 2015a; Eleje 2020; Goldenberg 2008; Hosny 2017; Kataoka 2006). A study evaluating the role of group B streptococci activity within the amniotic fluid following inoculation revealed an increased level of cytokines (interleukin (IL)‐1β and IL‐6), and prostaglandins (PG) (PGE₂ and PGE_2a) within the amniotic fluid (Gravett 1994). IL‐1β promotes IL‐6 and IL‐8 production, which in turn activates the synthesis of PGE₂ and PGF_2a, which trigger uterine contractions (Gravett 1994; Romero 2014b). Because IL‐1β is not found in the amniotic membranes of pregnant women who are in labour at term, IL‐1β is thought to be the key cytokine associated with intrauterine infection that can stimulate preterm labour (Sadowsky 2006). A positive response of the fetus to the infection of the amniotic cavity may also be contributory, as the intra‐amniotic infection could trigger the synthesis of corticotropin‐releasing hormone arising from the placenta and fetal hypothalamus, leading to elevated levels of fetal corticotropin and fetal cortisol which ultimately stimulate prostaglandin production (Gomez 1998; Romero 1998). Antibiotics work by blocking vital processes or by killing the bacteria, or stopping their multiplication. The body's natural immune system is energised in fighting the infection caused by the bacteria. Vaginal infection in early pregnancy is linked with spontaneous preterm delivery (Farr 2015; Sangkomkamhang 2015). For antibiotics to be useful in reducing spontaneous preterm labour and delivery from infectious causes, early administration of antibiotics in pregnancy is recommended (Lamont 2005). In some pregnancies, antibiotics may delay the onset of complications of labour, albeit that this is not regarded as tocolytic therapy. However, antibiotics are not currently part of standard care for the prevention of spontaneous preterm labour (ACOG 2003; Kenyon 2001). In a recent Cochrane Review assessing the effects of prophylactic antibiotics administered to women with preterm labour with intact membranes on the maternal and neonatal outcomes, Flenady 2013 concluded that there was no demonstrable benefit of using prophylactic antibiotics in women with preterm labour and intact membranes for important neonatal outcomes, although it may lead to a reduction in maternal infection. There could be harm to the children of mothers exposed to antibiotics on a short‐ and longer‐term basis; current evidence therefore does not support the routine use of antibiotics in women with preterm labour having intact membranes unless there are clear signs of infection (Flenady 2013; Kenyon 2001; Lamont 2005). In cases with obvious signs of infection, antimicrobial agents may be beneficial in averting the onset of preterm labour (Espinoza 2006; Gibbs 1992; Goncalves 2002; Mazor 1998).

Vaginal support pessary

The vaginal support pessary works by using processes that can affect the composition of the cervix and cervical plugs (Abdel‐Aleem 2013). The cervical mucus plug has 'viscoelastic' characteristics due to the presence of mucins, which are large glycoproteins (Lai 2009). The cervical mucus therefore assists the vaginal pessary by inhibiting viral replication and preventing large molecules and bacteria from ascending into the uterus (Lai 2009). Additionally, the cervical mucus has immunological characteristics such as innate and adaptive responses which make it possible for the vaginal pessaries to prevent bacterial infection through their stimulation of inflammatory response pathways (Goya 2012). Ideally, the cervix is tightly closed during a normal pregnancy with the aid of a cervical mucus plug gluing the opening shut. Thus, any defect or malfunction of the cervical mucus plug by cervical effacement could enhance the ascent of infection and preterm births (Becher 2009; Liem 2013). The vaginal pessary encloses the cervix and presses on the cervical canal, to inhibit the failure of the cervical mucus plug. The pessary changes the angle of elevation of the cervical canal, thereby correcting the cervical insufficiency by pointing forward in the vaginal axis. As a result of this, direct pressure on the internal os of the cervix is relieved, since the weight of the pregnant uterus is distributed onto the vaginal floor, retrosymphyseal osteomuscular structures, and Douglas cavity. This prevents premature rupture of fetal membranes and premature labour. Furthermore, the fetal head is prevented from descending and pressing on the internal cervical os (Liem 2013).

Reinforcing or second cerclage placement

Reinforcing or second or repeat cerclage placement may be useful because suture application in the McDonald’s cerclage procedures is usually at the level of the internal os of the cervix, with no allowance for possible changes in the width and shape of the cervix. The optimal tightening force for the sutures is currently unknown, and varies depending on the individual obstetrics caregiver’s experience. These differences in the tightening force may account for the lack of success of cervical cerclage performed by individual obstetricians (Hershkovitz 2008). The cerclage sutures could be applied under ultrasound guidance, which may enhance the success rate in women with cervical cerclage (Hershkovitz 2008).

Tocolytics

Tocolytics work by different mechanisms following cervical cerclage procedures. For example, magnesium sulphate lowers uterine contractions, but it is not clear how it performs its tocolytic action, although it is plausible that magnesium rivals calcium for entry into the muscle cells through voltage‐gated channels (Tan 2006). Antagonist therapy for calcium channels works by preventing the influx of calcium ions across the cell membrane, thereby lessening the smooth muscle vasculature tone (Sanborn 1995). Prostaglandins stimulate contractions of the uterine muscles by promoting gap junction formation in the myometrium and enhancing intracellular calcium within the cells (Van Vliet 2014). Prostaglandins are formed by cyclo‐oxygenase (COX), an enzyme that enhances the level of prostaglandins. There are two distinct versions of COX, i.e. COX‐1 and COX‐2. COX‐2 is uniquely linked with contractility of the myometrium. Prostaglandin synthetase inhibitors shorten the production of prostaglandin, thereby inhibiting a crucial labour pathway (Vogel 2014). Furthermore, intrauterine inflammation and infection play a crucial role in preterm labour, with the anti‐inflammatory action of prostaglandins being one of the reasons why prostaglandin inhibitors may be efficacious in prolonging delivery (Van Vliet 2014; Vogel 2014). The use of tocolytics such as indomethacin, a nonsteroidal anti‐inflammatory drug, may curb the uterine contractions precipitated by cervical manipulation and thereby prevent an accelerated stream to preterm delivery.

Tocolytics are usually given for 48 hours following cerclage placement. When a tocolytic is used, the subduing of contractions is usually partial in nature and tocolytics are often deployed to postpone delivery until some days later. Although it depends on the particular tocolytic used, the monitoring of the fetus or the mother is still paramount. For instance, the monitoring of blood pressure, especially when nifedipine is used as a tocolytic, is very important, since nifedipine lowers blood pressure. As it is unclear which of the tocolytic agents is a first‐line treatment, the use of any particular agent should be individualised and should be based on a number of factors such as the condition of the mother, gestational age of the fetus and the potential adverse effects (Tan 2006).

Progesterone

One process involved in preterm birth is the ill‐timed decrease in the function of progesterone, a condition that can lead to painless midtrimester shortening of the cervix (Romero 2014a). The available evidence suggests that decreased levels of plasma 17‐alpha hydroxyprogesterone caproate concentration are linked with a high frequency of spontaneous preterm delivery (Caritis 2014). Although it is unclear if progesterone prevents a cervix from shortening, the fact remains that sufficient levels of progesterone can prevent the production of prostaglandin with the subsequent lowering of uterine contractions (Hollier 2005), thereby maintaining uterine quiescence. This may be especially relevant following cervical cerclage procedures. Being a principal pregnancy hormone, progesterone also works by diminishing the sensitivity of uterine musculature to oxytocin, wedges adrenergic receptors and the synthesis of prostaglandin, and excites lymphocyte‐associated synthesis of progesterone‐induced blocking factor. Jointly, these processes expedite uterine stillness during the antepartum period, and regulate immune tolerance and cervical functions (Pustotina 2017). In women with a previous preterm birth without symptoms of uterine contractions in their index pregnancy, one study has shown that 17‐α‐hydroxyprogesterone caproate prophylaxis was not correlated with an effect on cervical length shortening (Durnwald 2009), nor does it seem to influence preterm delivery in women with history‐indicated cerclage (Mackeen 2013; Rafael 2011; Szychowski 2012). However, in another study, progesterone was associated with significant preservation of cervical length (O’Brien 2009). In women with preterm labour, 17‐α‐hydroxyprogesterone caproate injections prevented further cervical shortening (Facchinetti 2007). In one randomised study, post hoc analysis of data revealed that the frequency of early preterm birth is lower in women who had ultrasound‐indicated cerclage and hydroxyprogesterone caproate than in women who received either therapy alone (Berghella 2010).

Omega‐3 long chain polyunsaturated fatty acid

It has been suggested that omega‐3 long chain polyunsaturated fatty acids work by reducing gap junction formation and production of proinflammatory cytokines, thereby lowering the parturition rate among women with a prior history of spontaneous preterm delivery undergoing cervical cerclage treatment (Allen 2001; Olsen 2000; Olsen 2007). There are obvious variations in the metabolic derivatives of omega‐6 and omega‐3 polyunsaturated fatty acids, and their respective contributions in the classic Western diet provide a biological rationale for the statements that high levels of omega‐3 intake could lengthen the duration of pregnancy and slow down parturition (Harper 2010). For example, in one European multicentre study among women with previous spontaneous preterm births, women receiving omega‐3 supplement had a significantly reduced rate of recurrent preterm birth prior to 37 weeks of gestation (21.3% versus 33.3%, odds ratio (OR) 0.54, 95% confidence interval (CI) 0.30 to 0.98) and prior to 34 weeks of gestation (4.6% versus 13.3%, OR 0.32, 95% CI 0.11 to 0.89) (Olsen 2000).

Bed rest

Bedside advice plays an important part in reducing spontaneous preterm birth, especially following cervical cerclage procedures. The underlying mechanism of bed rest lies in the premise that strict obedience to bed rest advice often results in a reduction in preterm labour, since physical activity and hard work exhibited by pregnant women could be associated with spontaneous preterm delivery (Teitelman 1990), and in the belief that bed rest could reduce uterine contractions (Goldenberg 1994; Sosa 2015). Bed rest may account for the reduction in the prostaglandins in the blood. It is biologically plausible that high circulating prostaglandin metabolite levels might increase after cerclage placement, such that bed rest in addition to cervical cerclage may confer benefits (Novy 1987; Vitoratos 1996).

Treatments will prove successful if the relevant interventions are attuned to the definite pathophysiologic activities, and are applied at the right time for the women concerned. The use of some interventions in women who are not likely to deliver at preterm gestation is inappropriate. Understanding of the heterogeneity of preterm labour and delivery, with realistic expectations, is paramount to the process.