Labor induction with prostglandins

Happy new year & Best wishes : 

Happy new year & Best wishes AGARTALA GOVT. MEDICAL COLLEGE, AGARATALA

Role of prostglandin in cervical ripening : 

Role of prostglandin in cervical ripening jahar lal baidya, assistant professor, agmc, tripura

definitions: : 

definitions: Ripening or ripeness: Process of softening, shortening and partial dilatation Induction: initiation of uterine contraction Augmentation: stimulate uterine contraction Bishop’s score (1964) – accepted method of assessing cervical ripening Ripening is first step of induction Tansvaginal USG cervical length is better predictor than any Bishop score parameter

definitions : 

definitions Uterine Tachysystole: six or more contractions in 10 mins without any FHR abnormalities Uterine Hyperstimulation: uterine tachysystole with concomitant abnormal FHR pattern Successful induction: achieves active phase(>4 cm dilatation with regular contractions) with in 24 hrs and later achieves uncomplicated vaginal delivery Failed induction: should not be diagnosed until after 12 hrs of Oxytocin after membrane rupture in active phase with reassuring FHR pattern

Histology of cervical ripening : 

Histology of cervical ripening Composed of collagen type I, III, IV and smooth muscle (10 to 15 %) Before onset of labor Collagen content decreases Water & non collagen, non elastin proteins increase

Histology of cervical ripening….contd. : 

Histology of cervical ripening….contd. Production of cytokines & extravasations of neutrophils into cervical stroma Degranulation of neutrophils releases proteases Proteolytic enzymes responsible for degrading collagen & rearrangement of collagen cells Apoptosis of smooth muscle cell

PGs in use: : 

PGs in use: PG F2 alpha (Carboprost): Extra amniotic -not used PG E2(Dinoprostone): Gel, tablet, insert PG E1(Misoprostol): Tablet

Mechanism of action - PGs : 

Mechanism of action - PGs PGs are formed enzymatically from phospholipids & arachidonic acid found in most tissues of body Local hormone: acts locally Myometrium : PG I2 & PG E2 Decidua: PG F2 alpha Causes Dissolution of cervical collagen bundle Increases cervical sub mucosal water content Stimulates smooth muscle contraction of cervix & uterus Increases gap junction formation

Advantages of PGs : 

Advantages of PGs Enhanced cervical ripening Decreased need for Oxytocin for induction Decreased Oxytocin induction time Reduced amount of Oxytocin needed for successful induction PGs is superior to low dose Oxytocin

Assessment of effectiveness : 

Assessment of effectiveness Changes in effacement & dilatation Vaginal delivery within 24 hrs Requirement of augmentation Incidence of Cesarean section rate Uterine hyper stimulation Neonatal morbidity & Perinatal death Serious maternal complications

PG E2 : Dinoprostone : 

PG E2 : Dinoprostone Dinoprostone vaginal insert – (Not available in INDIA ) 10 mg: 0.3 mg/hr for max of 12 hrs Insert into posterior fornix Stored at - 20 degree Celsius Does not require warming Can be removed once labor starts or any complication Oxytocin can be started 30 -60 min after removal of insert Expensive

Slide 12: 

DINOPROSTONE gel: Prefilled syringe with applicator 2.5 ml gel with 0.5 mg dinoprostone Intracervical application May repeat every 6 hrs maximum of 3 doses/24hrs(1.5 mg) Required refrigeration and must be warmed to room temp. Must wait 6-12 hrs before starting Oxytocin Reliable but expensive PG E2 : Dinoprostone Available in INDIA

PG E2 Tablet : 

PG E2 Tablet 3 mg 6-8 hrly to a maximum dose of 6 mg Dose should be varied according to patient’s cervical score Optimal dose, route of administration & frequency is debatable Oxytocin induction or augmentation 12 to 18 hrs later after the final dose

PG E2: Summary : 

PG E2: Summary PG E2 mainly regarded as cervical ripening agents & are not reliable as labor induction agents Needs refrigeration : gel, vaginal insert Expensive

PG E1: MISOPROSTOL : 

PG E1: MISOPROSTOL MISOPROSTOL: Synthetic PGE1 analogue Route: posterior fornix, rectal, oral, sublingual 25 mcg tablet May repeat in 3-6 hrs for a max. 6 doses Stable at room temp Oxytocin can be administered 4 or more hr after last dose Inexpensive

PGE1 – dose & administration : 

PGE1 – dose & administration Wide variation (max) : 50 to 600 mcg Vaginal route: 25 mcg Q 3 to 4 hr, max 150 to 200 mcg 50 mcg Q 3 to 4 hr, max 200 to 400 mcg 100 mcg Q 12 hr, max 200 mcg Oral route 50 mcg Q 4 hr, max 250 mcg Sublingual 50 mcg Q 4 hr, max 250 mcg

PGE1: Benefits & concerns : 

PGE1: Benefits & concerns Benefits: Concerns: Higher rate of VD in 24 hrs Reduced need for augmentation of labor Reduced I-D interval Less cost No need for refrigeration Uterine hyper stimulation (5-15%) MSAF (5 -10%) Reports of uterine rupture Optimum dosing and interval not well established Legal status No reduction in CS rate

Summary – PGE1 : 

Summary – PGE1 Effective agent for cervical ripening & induction of labor Lower dose is safe for both mother & fetus Contraindicated in previously scarred uterus

Summary – PGE1 : 

Summary – PGE1 Vaginal route is preferable to oral route Optimum dose is not established – 25 mcg @ 3 to 4 hrs interval is widely used Uterine hyper stimulation , non reassuring FHR, MSAF, uterine rupture are common concern

To be precise…….. : 

To be precise…….. Apart from its cost savings, stability at room temperature and rapidity of action Is no stronger than other prostaglandin preparations

Controversies about PGs : 

Controversies about PGs Potent uterotonic side effects Precipitate labor Abruption Non reassuring FHR patterns Uterine rupture Need hospitalization Continuous monitoring is essential Not to be used in women with uterine scar

Placebo Vs. PG E2 : 

Placebo Vs. PG E2 PGE 2 gives Satisfactory & significant ripening Increased incidence of vaginal delivery with in 24 hrs No decrease in CS rate Bouvain, Kelly, Irion 2008

Mechanical methods Vs. PG E2 : 

Mechanical methods Vs. PG E2 No reduction in CS rate Lower incidence of hyperstimulation Bouvain et al 2001

PG E2 : Vaginal Vs. Intracervical : 

PG E2 : Vaginal Vs. Intracervical Vaginal PG E2 as “gold standard” Can be removed once labor starts or complications develop Intracervical PG E2 – more cumbersome Intra-cervical : more effective & significant cervical ripening Interestingly intra cervical route appears to be associated with lower risk of hyper stimulation

PGE1 Vs. Oxytocin : 

PGE1 Vs. Oxytocin More effective than Oxytocin for induction Increased incidence of uterine hyperstimulation No difference in maternal or Perinatal outcome

PG E1(Vaginal) Vs. PG E2 (both routes) : 

PG E1(Vaginal) Vs. PG E2 (both routes) PG E1 more efficient cervical ripening agents PGE1 achieves 30% more vaginal delivery Less need for augmentation with PGE1 Higher incidence of uterine hyper stimulation with PGE1 Inconsistent reports about CS delivery rate Hofmeyr & Gulmezoglu 2002

Oral Vs. Vaginal PGE1 : 

Oral Vs. Vaginal PGE1 Oral PGE1 Vaginal PGE1 More rapid & more pronounced Similar uterine activity Similar induction delivery interval Fewer CS Slower but sustained action for longer Less augmentation No difference in neonatal outcome Both efficacious ripening & induction agent Vaginal route misoprostol have sustained plasma concentration of active metabolite – misoprostol acid leading to longer duration of action

PGE1 : Low Vs. High : 

PGE1 : Low Vs. High Low Dose High Dose 25 mcg More Oxytocin use Lesser uterine activity Lesser MSAF 50 mcg Labor induction more efficacious Shorter induction delivery interval Increased uterine activity ACOG recommends 25 mcg of PGE1 should be considered for initial dose

Buccal Vs Sublingual : 

Buccal Vs Sublingual Sublingual Shorter onset Longer duration Greater bioavailability

PGs in special circumstances : 

Previous scarred uterus PROM Fetal death PGs in special circumstances

PGs in special circumstances : 

PGs in special circumstances Previous scarred scar Uterine disruption is greater with induced labor than with spontaneous labor (0.65% Vs 0.4%) Misoprostol should not be used(ACOG)

PGs in special circumstances : 

PGs in special circumstances PROM Intra vaginal Misoprostol is found to be more effective than local PGE2

PGs in special circumstances : 

PGs in special circumstances IUFD Use of Misoprostol with or without priming Mifepristone - revolution in termination of IUFD Addition of Mifepristone significantly shorten induction delivery interval Dose: PG E1 25 to 100 mcg vaginally @ 4 hrs interval + Mifepristone 200 mg orally

Specific clinical recommendations & conclusions : 

Specific clinical recommendations & conclusions Label A(I a) PGs are effective for cervical ripening & induction Intra vaginal PGE2 is preferable to Intracervical PGE2 as it is less invasive PG tablets are equally effective as PG gel but tablets offer financial savings PG E1 appears to be cheap & effective inducing agent, safety issues are probably related to dose or route

Specific clinical recommendations & conclusions : 

Specific clinical recommendations & conclusions Label A Regardless of Bishop score, the most efficient method of induction before 28 wks appears to be vaginal Misoprostol The use of Misoprostol to be avoided in women with previous CS or any major uterine surgery

Specific clinical recommendations & conclusions : 

Specific clinical recommendations & conclusions Label B Oxytocin to be started at least 6 hrs later following PG administration (III) Fetal well being should be established once contraction begins following insertion of PGs(III) There are insufficient safety data for outpatient use of PGs

Levels of Recommendations: : 

Levels of Recommendations: A: The recommendation is based on good and consistent scientific evidence. B: The recommendation is based on limited or inconsistent scientific evidence. C: The recommendation is based primarily on consensus and expert opinion.

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