Labor induction: history, physiological background, different methods of labor induction.

Labor is a process through  which the fetus moves from the  intra uterine to extra uterine environment . It is a clinical diagnosis defined as the initiation and perpetuation of uterine contractions with the goal of producing progressive cervical effacement and dilatation and expulsion of fetus and after births.

 Induction of labor :

Refers to the process whereby uterine contractions are initiated  by medical  means before the onset of spontaneous labor with the intension to have vaginal delivery. Occasionally it may end in cesarean section or instrumental delivery.

Historical introduction :

    The need to time delivery has been recognized and practiced for centuries. Although the indications have clearly changed during the past 200 yrs from a need to expel a dead fetus to the pre-emptive action to reduce the threat to fetal or maternal health. Effective and safe methods of achieving delivery   always have been the primary objectives.

                  A number of folkloric or old midwives tales used at those days and are still used today by women to encourage their labor to start.  Among the more common approaches are  frequent walking,   vaginal intercourse, participating in heavy exercise, consumption of laxatives, spicy foods or herbal tea, nipple stimulation and administration of a purgative.

                                  Most methods of inducing labor before the last half century involved mechanical manipulations, including Galvinism, repeated pressurized douches, extra-amniotic aqua pica, tents, bougies, catheters.The issue of threats, incantations and chants was doubtless popular when nothing else was on hand. While the administration of potions and later castor oil, quinine and posterior pituitary extract were also utilized.

                     Less well known approaches include taking a hot both, dancing, eating Chinese food, drinking warm gin or cranberry juice and riding in a car over a bumpy road.

                     During the last 40 yrs, labor induction has mostly involved combining the recognized advantages of physical manipulation with a pharmacological myometrial stimulant like oxytocin.

                                         For  the last 30 yrs the state of uterine cervix has been recognized as having a major influence on success of attempts to induce labor. It is common practice to describe methods of labor induction used when the cervix is unripe or unfavorable and those used when cervix is favorable. In reality it is continuum.

                                In  the 1980s and 1990s patient’s acceptance of when and how delivery was achieved became a significant and sometimes over powering consideration, but has not necessarily always been in the long term best interests of mother or fetus.

                       In some countries the fear of legal redress if the pregnancy outcome is not entirely favorable has become so concerning that the patient demands are frequently acquiesced to and in many cases, requests for delivery  by cesarean section are agreed although there is no clear medical indication.      

 Physiological back ground:

The cervix is essential in maintaining uterine stability during pregnancy. To achieve this, the maintenance of cervical shape and consistency is imperative since cervical ripening is a physiological process occurring throughout the latter weeks of pregnancy and is completed with the onset of labor. When delivery is necessary and ripening has not had time to occur, or has failed to be initiated, the natural process has to be accelerated.

The cervix possesses a unique construction  to enable it to perform its various roles.

It consists predominantly of a stromatous body of connective tissue that can be subdivided into a superficial loose zone and deeper dense stromal zone. The main element of this connective tissue are collagen together with a small amount of elastic tissue and an even smaller component of muscle fibers. The collagen is composed of dense regular fibrils arranged in parallel bundles held together by cross-links, with a few interspersed mast cells and other cellular elements.

The ground substance is composed of proteoglycan complexes consisting of glycosaminoglycan side chains (GAGs) on core proteins linked to a hyaluronic acid chain that bind tightly. The dominant GAGs in the cervix are dermatan sulphate and chondroitin sulphate, both of which contain hyaluronic acid conferring additional binding strength and have hydrophilic properties.

In the ground substance fibroblasts with numerous long cytoplasmic processes radiating from one cell to another are found these are possibly similar to myometrial gap junctions, infiltrating the ground substance.

With the advance of pregnancy, increased vascularity is seen and fibroblasts become secretory, white cells and macrophages migrate out of vessel walls in to the cervical stroma with an increase in water content. There is a reduction in collagen content and relative increase the glucoronic acid  containing GAG heparin sulphate that binds much less strongly.  Enzymatic beak down of collagen fibrils by collagenases or matrix metalloproteinases  produced by fibroblasts and polymorphonuclear leukocytes alongside leukocyte elastase which catabolises elastin, leads to increased cervical compliance.

                              The precise mediation and inter- relationships remain to be elucidated , but the prostaglandins and their synthase inhibitors are closely implicated with the known increase observed as pregnancy advances.

                                Significantly there is reasonably strong evidence that the process of cervical ripening will occur without any detectable uterine contractions.

 Cytokines , notably IL-8 or platelet activating factor PAF and monocyte chemotactic protein - 1 (MCP-1)  have been proposed as possible interactants in the remodeling process involved in cervical ripening, as has nitric oxide,synthesized by macrophages, myometrium and the cervix.

 As yet , the precise role if any, for these agents in this physiological process  remains to be elucidated.

Current methods of inducing labor :

The methods of induction of labor used at present are,

A. Mechanical methods

B. Pharmacological methods

C. Surgical methods

                                                                                                                                  

A. Mechanical methods:

All mechanical modalities share a similar mechanism of action, that is

exerting some form of local pressure that stimulates the release of

prostaglandins.

Eg. Hygroscopic dilators 

Laminaria japonicum and synthetic osmotic dilators  eg. Lamicel.

Balloon catheter

B. Pharmocological methods:

Oxytocin :

 Du Vignaeaud synthesized syntocinon from the nona- peptide oxytocin in the 1950s . It has been used by intravenous infusion for the majority of women having their labor induced. 

Although still used as primary induction agent occasionally, it is more frequently given to assist the induction process using prostaglandins when the cervix is unfavorable or an adjunct to low amniotomy in more favorable cases.

         These are usually set as starting rate around 1 to 4 mu / min and increases variably, either arithmetically  or logarithmically at 15 to 30 min intervals often to a maximum of around 32 mu/min  or  until satisfactory labor has been established, occasionally higher rates may be required. Because of the ease of turning off the oxytocin infusion, they suggested that this method may have a preferential role in high risk patiens whose fetuses are at increased risk for intolerance of labor.

Prostaglandins :

By the mid 1980s prostaglandins had become established as the most effective pharmacological agents for inducing labor when the cervix is unripe.  A variety of administration routes had been employed during the preceding years, including  oral , intravenous, sublingual, rectal, intra amniotic, extra amniotic, intra cervical,  and vaginal administration. The vaginal route is found to be the most acceptable, providing good efficacy and acceptability for the parturient and is now the preferred method of choice. Prostaglandin E₂ (dinoprostone) is licensed for the use of labor induction in the cases of viable pregnancies.

Two forms of PGE₂  are available commercially. The first is formulated as gel and is placed inside the cervix but not above the internal os. The application  (3g gel / 0.5 mg dinoprostone) can be repeated in 6 hrs, not to exceed 3 doses in 24 hrs.

 The second form is 10 mg of dinoprostone embedded in a mesh and is placed in the posterior fornix of vagina, this allows for control release of dinoprostone over 12 hrs, after which it is removed.

Prostaglandin E₁ analog (misoprostol)  available in tablet form for induction of labor was described recently in a series of articles. This is a synthetic prostaglandin, which is marketed as an antinuclear agent under the trade name cytotec.  25 or 50 micro g   placed in the posterior fornix, has been shown in several studies to be quite effective in inducing cervical ripening and initiation of  labor. The application of medication can be repeated every 4 -6 hrs up to 5 doses.

                                  

The major risk of above prostaglandin preparation is uterine poly systoly, hyper-stimulation, meconium stained liquor   and fetal distress. The women and fetus must be monitored for contractions, fetal wellbeing and changes in Bishop score.

                     Finally, it was demonstrated that the combination of oxytocin induction preceded by dinoprostone insert is safe, and this significantly shortens induction to delivery time.

Recently explored methods:

Anti progesterone   eg.  Mifepristone

Ostrogens

Relaxin

Nitric oxide

C. Surgical methods :

Membrane sweeping

Amniotomy

                                                                                                                                  

Natural and complementary medicine methods:

Homeopathy

Breast stimulation

As a general principle the simplest inductions are those performed when the cervix is ripe and probably precede the spontaneous onset of  labor by a few hours to a day or two. And for the most difficult inductions, when the cervix is very unripe, a combination of a pharmacological agents, possibly involving more than one drug along with mechanical stimulus may be needed.