progesterone in preterm birth
TRANSCRIPT
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
• Accounts for more than 85% of all perinatal morbidity and mortality, responsible for:
Spong, Obst Gynecol 2007
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.
• 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.
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
• However, a larger trial (600+), history of PTB, vaginal progesterone gel 90 mg daily, starting at 18-23 wks, didn’t find similar results.
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