progesterone in preterm birth

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Progesterone and preterm birth prevention translating clinical trials Mentor: Dr. Nora Al-Qahtani Consultant Ob/Gyn KSMC, Maternity Hospital Presenter: Dr. Hend M. Hamido MBBCh, MSc Ob/Gyn, Egypt KSMC, Maternity Hospital

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Progesterone and preterm birth prevention

translating clinical trialsMentor:

Dr. Nora Al-QahtaniConsultant Ob/Gyn

KSMC, Maternity Hospital

Presenter:

Dr. Hend M. HamidoMBBCh, MSc Ob/Gyn, Egypt

KSMC, Maternity Hospital

• Complicates 1 in 8 births in developed countries.

• Accounts for more than 85% of all perinatal morbidity and mortality, responsible for:

Spong, Obst Gynecol 2007

• Major causes of preterm birth

Although the ability of obstetric care providers to identify women at high risk for preterm birth has improved, due to

introduction of TV cervical length measurement, and cervico-vaginal fetal

fibronectin testing…

Efforts to prevent preterm birth, have been largely

unsuccessful.

• Steroid Hormone• Isolated in 1934 from the corpus luteum• �Natural or Synthetic formulations (Oral, IM,

and Vaginal )• �Used for: • • Hormonal supplementation• • Replacement• • Contraception

• Synthetic progesterone:• HYDROXYPROGESTERONE CAPROATE

(17P)• FDA approved 3/Feb/2011• The only FDA approved medication to reduce

the risk of PTB in certain situations.

Rational behind use of progesterone to prevent preterm birth

• In the 1st trimester, progesterone produced by the corpus luteum is critical to the maintenance of early pregnancy, until the placenta takes over this function at 7-9 wks of gestation.

• Removal of the source of progesterone (CL), or administration of progesterone receptor antagonists, readily induces abortion before 7 wks of gestation.

• Its role in later pregnancy is less clear, it maybe important to maintain uterine quiescence, by limiting production of stimulatory prostaglandins, and inhibiting the expression of contraction associated protein genes (oxytocins, prostaglandins, and gap junctions) in the myometrium.

The hypoThesi

s

Myometrial activity associated with preterm labor results mainly from loss of the inhibitory effect of

pregnancy on the myometrium, rather than an active process of release of uterine stimulants.

The onset of labor, both at term and preterm is associated with, a functional withdrawal of progesterone activity at the uterine level.

Exogenous progesterone, will offset withdrawal and preterm

birth

Let’s examine the evidence…

• However, a larger trial (600+), history of PTB, vaginal progesterone gel 90 mg daily, starting at 18-23 wks, didn’t find similar results.

• So, let’s translate all these trials into clinical practice

Eligibility for 17P:

•History of spontaneous PTB <37 wks gestation.•Singleton pregnancy.•Initiate treatment between 16 wks and 20 wks 6days

Exclusion:•Known fetal

anomaly.•Current or

planned cervical cerclage.

•Hypertension.•Seizure disorder.

17P is not for women with:•Multi fetal pregnancy.

•Short cervix and NO prior PTB

•Previous medically indicated PTB

Level I and III evidenceLevel A recommendation

There is insufficient evidence to recommend progesterone in

singleton gestation, with no prior PTB, and unknown CL

Level I evidenceLevel A recommendation

In singleton gestation, no prior SPTB, and TVU CL ≤ 20 mm, at ≤ 24 wks. Vaginal progesterone (90 mg gel or

200 mg supp.) is associated with reduction of PTB, and perinatal

mortality and morbidity

Level I and III evidenceLevel B recommendation

Universal TVU CL screening of singleton

gestation without history of PTB is subject of debate.

Level I and III evidenceLevel A & B recommendation

In singleton gestation with prior SPTB at 20-36W+6 days, 250 mg

IM weekly of 17P to start at 16-20 weeks till 37 weeks

Level I, II, and III evidenceLevel B recommendation

Progesterone is not associated with prevention

of PTB in multiple gestation, PTL, or PPROM

These recommendations coincide with those from uptodate,

however…