Progesteron for Preterm Labour Prevention Prof.Dr.S.Cansun DEM İ R President of FGOM 16.May.2013-Antalya

Preterm labour Delivery before 37 weeks of gestation  % Perinatal Mortalit y  50 % Long term morbidity

Progesteron in preterm labour ACOG, suggests progesteron for the prevention of preterm labour. Its mechanism is not well known What are the indications for progesteron ? What must be the type of progesteron and, route of usage and dosage ?

Progesteron, blocks the Prostaglandin F2 α and α -adrener gic re ceptors which is necessary for uterus contractility and leads to uterine relaxation. Decreases the oxytocin receptors in uterus, Up regulation of nitric okside and blockage of intracellular gap junctions lead to myometrial relaxation.

Erny et al.had showed the tocolytic effect of oral micronized progesterone in mg oral mi c ronize d progesteron usage decreasespreterm labour by 88 %. Pla c ebo is found to be effective in 42 %.

Combination of m i c ronize d progesteron with, β-adrenergic agonists, leads to decrease of the dosage of β- agonist. Its tocolytic effect is similar. Cost and risk decreases. It may lead to increase in hepatic enzymes.

Natural Progesteron Natural progesteron begins from,18-25 th. weeks, given mg /daily and generally used vaginal ly. Oral mi c ronize d progesteron is an alternati ve. There is no hepatic first pass effect by vaginal route and biotolerability is better. Endometrial effect is higher by vaginal route comparing to parenteral usage. There is uterin first-pass effect.

Synthetic Progesteron (17- α -hidroksiprogesteron) Synthetic progesteron is used by İ.M. Route. Do sage changes from mg 1-3 times a week. There is side effects in 50 % of the cases. In the 4 year follow-up of the babies no long term effects, genital anomaly or sexuality role changes was noticed.

Indications of Progesteron for preterm labour History of preterm labour Short cervix Multipl pregnancy Threatened preterm labour

History of preterm birth PTL decreases % in patients with a history of previous PTB. There is a decrease in newborns < 2500 gr 3-40 %. Mean birth weight was 475 grs more in progesterone group.

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Dodd JM.Progesterone for the Prevention of Preterm Birth Obstetrics &Gynecology,2008,112,

Patients with PTH history Dr.Elçin Erçetingöz Yüksek Riskli gebelerde Preterm Eylem ve Do ğ umun Önlenmesinde Mikronize Progesteronun İ ntravajinal Kullanımı Uz m anlık Tezi Zeynep Kamil Hastanesi, 2007

Short Cervix Cases with ≤ 15 mm cervical length, administration of 200 mg vaginal progesteron decreases preterm birth < 34 weeks by %.

Dodd JM.Progesterone for the Prevention of Preterm Birth Obstetrics &Gynecology,2008,112,

Fonseca E.B. et al. Progesterone and the risk of Preterm Birth am on g Women with a Short cervix NEJM, 2007,357;5,

Multipl Pregnancy In unselected twin pregnancies usage of İ.M. 17P does not influence deliveries <35 weeks. 200 mg vaginal progesteron does not effect multipl pregnancies with shortened cervix.

Dodd JM.Progesterone for the Prevention of Preterm Birth Obstetrics &Gynecology,2008,112,

Birth in Twin pregnancies before 37 weeks Dr.Elçin Erçetingöz Yüksek Riskli gebelerde Preterm Eylem ve Do ğ umun Önlenmesinde Mikronize Progesteronun İ ntravajinal Kullanımı Uz m anlık Tezi Zeynep Kamil Hastanesi, 2007

Arrested Preterm Labour Vaginal progesteron with a dosage of 400 mg/day was given to 70 patients with arrested (threatened) labour. Birth was prolonged for 12 days. Low birth weight RR 0.52, RDS risk NICU admission decreases from 39 % to ’ 24 %. Neonatal sepsis decreases from 18 % to 5 %.

Combined results without risk factors Preterm labours are prevented and low birth weight decreases by %. IVH decreases 75 % and NEC decreases. Progesteron dosage was not found to be significant.

PTB in Progesteron Dr.Elçin Erçetingöz Yüksek Riskli gebelerde Preterm Eylem ve Do ğ umun Önlenmesinde Mikronize Progesteronun İ ntravajinal Kullanımı Uz m anlık Tezi Zeynep Kamil Hastanesi, 2007

NICU admission

Take Home Message 1. Patients with PTB, usage of vaginal progesteron > 100 mg /daily dose after 24 weeks is found to be effective in prevention of PTL. 2. In patients with short cervix (≤ 15 mm) usage of 200 mg vaginal progesteron was found to be effective.

3. In twin pregnancies routine usage of progesteron is not indicated but for selected cases with PTB history or short cx may be used. 4. In arrested PTL cases daily 400 mg vaginal progesteron may be used.