2. ROLE OF PROGESTERONE IN PREGNANCY MAINTENANCE & LATER IN PREGNANCY
Dr. M.Moshfeghi
fellowship of perinatology
OBS&GYN
RUYAN INSTITUTE

3. refers to a delivery that occurs before 37 0/7ths
 Preterm birth
refers to a delivery that occurs before 37 0/7ths
refers to a delivery that occurs before 37 0/7ths

4. The percentage of newborns delivered at very low birthweight has declined only minimally 1.46 percent in percent in 2010 preterm birth continues to be a major determinant of short- and long-term morbidity in infants and children
has declined only minimally
1.46 percent in 2008
1.45 percent in 2010
major determinant of short- and long-term morbidity in infants and children

5. functional progesterone withdrawal
pathophysiologic events occurring with mother, placental fetal compartment. Therefore, functional progesterone withdrawal failure of transformation of the spiral arteries fetal stress due to uteroplacental vascular insufficiency
functional progesterone withdrawal

6. challenge of distinguishing
true labor (contractions result in cervical change) from false labor (contractions that do not result in cervical change).
challenge of distinguishing

7. Transvaginal ultrasound
the most reliable method for measuring cervical length
Is the most reliable method for measuring cervical length. In symptomatic and asymptomatic preterm patients, a short cervix (<30 mm) is predictive .
In symptomatic and asymptomatic preterm patients,

8. Progesterone supplementation to reduce the risk of spontaneous preterm birth
ROLE OF PROGESTERONE IN PREGNANCY MAINTENANCE EFFICACY OF PROGESTERONE FOR PREVENTION OF PRETERM BIRTH

9. Efforts to delay delivery have been largely unsuccessful.
Preterm birth complicates 1 in 8 over 85 percent of all perinatal morbidity and mortality. Efforts to delay delivery have been largely unsuccessful. much attention has focused on preventative strategies.
Efforts to delay delivery have been largely unsuccessful.
much attention has focused on preventative strategies

10. Sonographic imaging
imaging of the cervix across gestation has enhanced our understanding of cervical performance Cervical effacement is one of the first steps in the parturition process, preceding labor by at least four to eight weeks.
Cervical effacement
is one of the first steps in the parturition process, preceding labor by at least four to eight weeks.

11. Sonographic imaging it can be seen by ultrasound,
Effacement begins at the internal cervical os and proceeds caudally, . ,
it can be seen by ultrasound,
but is NOT by digital or visual examination

13. less reproducible; . Transabdominal images of the cervix are
thus, they should not be used for clinical management

14. high-risk pregnancies, prior second trimester losses
Timing CL before 14 weeks have limited clinical value . However, high-risk pregnancies, prior second trimester losses and/or large (or multiple) cone biopsies, cervical shortening has been seen as early as 10 to 13 weeks Reproducible measurement of at about 14 weeks, when the cervix normally becomes distinct from the lower uterine segment.
high-risk pregnancies,
prior second trimester losses
and/or large (or multiple) cone biopsies,
cervical shortening has been seen as early as 10 to 13 weeks

15. With proper technique, the intra- and inter-observer variabilities are <10 percent.

16. after 28 to 32 weeks. after 28 to 32 weeks.
 Cervical length is
stable between weeks,
declines substantially
after 28 to 32 weeks.
stable between weeks
after 28 to 32 weeks.

17. Between about 14 and 28 weeks , the length of the cervix is described by a normal bell-shaped curve :
Between about 14 and 28 weeks , the length of the cervix is described by a normal bell-shaped curve :
2nd centile at 15 mm
5th centile at 20 mm
10th centile at 25 mm
50th centile at 35 mm
90th centile at 45 mm

18. the median cervical length is
40 mm before 22 weeks,
35 mm at 22 to 32 weeks,
30 mm after 32 weeks.
Cervical length is not significantly affected by parity, race/ethnicity, or maternal height

19. The significance of differences
in the rate of cervical change (eg, 30 mm to 20 mm Versus 20 mm to 15 mm over two weeks) for prediction of preterm birth is unclear,

20. ROLE OF PROGESTERONE IN PREGNANCY MAINTENANCE
 — Progesterone initially produced by the corpus luteum.
is critical for the maintenance of early pregnancy
the placenta takes over this function at 7 to 9 weeks
removal of the source of progesterone (the corpus aluteum) or administration of a progesterone receptor antagonist
induces abortion before 7 weeks (49 days) of gestation.

21. The role of progesterone later in pregnancy
, less clear.
maintaining uterine quiescence
, less clear. maintaining uterine quiescence , the onset of labor both at term and preterm is associated with a functional withdrawal of progesterone activity at the level of the uterus
a functional withdrawal of progesterone activity at the level of the uterus

22. The role of progesterone later in pregnancy
Progesterone has been shown to prevent apoptosis in fetal membrane explants, under both basal Prevent pro-inflammatory conditions may help to prevent preterm premature rupture of membranes (PPROM),
prevent apoptosis in fetal membrane
Prevent pro-inflammatory conditions
may help to prevent preterm premature rupture of membranes (PPROM),

23. EFFICACY OF PROGESTERONE FOR PREVENTION OF PRETERM BIRTH
depends primarily on
appropriate patient selection
reduces the risk of preterm birth by one-third

26. prior spontaneous singleton preterm birth, normal cervical length
Singleton pregnancy,
prior spontaneous singleton preterm birth, normal cervical length
Progesterone supplementation? YES Hydroxyprogesterone caproate 250 mg IM weekly beginning between 16 and 20 w and continuing through 36 w of gestation or until delivery and monitor cervical length. Short (<25 mm) cervix → perform cerclage

27. prior spontaneous twin preterm birth, normal cervical length
Singleton pregnancy,
prior spontaneous twin preterm birth,
normal cervical length
Progesterone supplementation indicated? Possibly Hydroxyprogesterone caproate 250 mg weekly beginning 16 and 20 weeks through 36 weeks or until delivery and monitor cervical length. Short (<25 mm) cervix → perform cerclage

28. Yes Singleton pregnancy, no prior spontaneous preterm birth,
short cervix (≤20 mm)
Progesterone supplementation indicated?
Yes

29. Progesterone suppository 90 to 200 mg vaginally each night from time of diagnosis through 36 weeks. a 100 mg micronized progesterone vaginal tablet an 8 percent vaginal gel containing 90 mg micronized progesterone per dose. Both preparations are commercially available in US, but not approved for prevention of preterm birth in cervical shortening.

30. Multiple pregnancy (twins or triplets) without prior preterm birth, normal cervical length
No No progesterone, no cerclage

31. Twins, prior preterm birth
Possibly Hydroxyprogesterone caproate 250 mg IM weekly beginning between 16 and 20 weeks of gestation and continuing through 36 weeks of gestation or until delivery.

32. Twins, short cervix
Possibly Vaginal progesterone, no cerclage

33. Twin pregnancy
the efficacy of high dose vaginal progesterone (400 mg/day) no more effective than lower dose therapy (200 mg/day) or a placebo,

34. Spontaneous twin preterm birth in prior pregnancy
YES We suggest 17P supplementation for women with a singleton pregnancy who have had a prior preterm birth, singleton or twin.

35. No Preterm premature rupture of membranes No
Positive fetal fibronectin test No
Undelivered after an episode of preterm
labor No

36. significant difference
By monitoring with an external tocodynamometer once a week for 60 min , significant difference in the frequency of spontaneous uterine contractions between the two groups, SO progesterone supplementation may exert its effect by maintaining uterine quiescence in the latter half of pregnancy.
significant difference
progesterone supplementation may exert its effect by maintaining uterine quiescence in the latter half of pregnancy

37. if all eligible women had received progesterone prophylaxis, it would only have reduced the overall preterm birth rate in the United States by approximately 2 percent

38. after placement of a cerclage
Cerclage — a prior preterm birth, continuing 17P supplementation has not been proven to be useful, ?????????

39. women with a history of preterm birth due to PPROM
YES,
appear to benefit from progesterone supplementation in subsequent pregnancies;

40. NO NO Acute preterm labor do not routinely recommend progesterone .
do not routinely recommend progesterone
supplementation in this setting. NO NO

41. NO Uterine anomaly or ART
NO  — There are no data
on the effectiveness of progesterone therapy for prevention of preterm birth in uterine malformations
OR who conceive with assisted reproductive technology NO

42. SIDE EFFECTS AND ADVERSE EFFECTS
three-fold increase in risk of developing gestational diabetes in some studies

43. Progesterone exposed infants
less perinatal morbidity,
reduced rates of
necrotizing enterocolitis,
intraventricular hemorrhage,
need for supplemental oxygen.
There was no evidence of virilization of female offspring, which is a theoretic concern of this therapy

44. Several studies have reported a nonstatistical increase in risk of miscarriage and stillbirth in pregnancies exposed to progestins but others could not confirm this observation or observed a nonstatistical decrease in these risks

45. PROGESTERONE PREPARATIONS, ROUTES, AND DOSES —
have been effective at reducing the risk of preterm birth
compared with no treatment/placebo
all formulations

46. Evidence is insufficient to define the optimum gestational age for starting treatment

47. 17-alpha-hydroxyprogesterone (17P)
17-alpha-hydroxyprogesterone (17P) natural progesterone metabolite made by the corpus luteum and placenta minimal to no androgenic activity. intramuscularly. 25 mg every five days to 1000 mg weekly, beginning as early as 16 weeks of gestation. We use a 250 mg dose

48. Standard contraindications to progesterone administration include
hormone-sensitive cancer
, liver disease,
uncontrolled hypertension .

49. for the prevention of preterm birth
This is the first time that the FDA has approved a medication , and represents the first approval of a drug specifically for use in pregnancy in more than 15 years.
for the prevention of preterm birth

50. Vaginal progesterone preparations
Natural progesterone is typically administered vaginally. high uterine bioavailability since uterine exposure occurs before the first pass through the liver. few systemic side effects, but vaginal irritation needs to be administered daily. Doses of 90 to 400 mg , beginning as early as 18 weeks of gestation. We use 100 mg administered vaginally each evening; however, in some areas a 200 mg suppository may be more readily available and less costly
Vaginal progesterone preparations

51. An oral micronized preparation of natural progesterone also exists
An oral micronized preparation of natural progesterone also exists. Daily doses of 900 to 1600 mg have been given. Reported side effects include sleepiness, fatigue and headache
Oral progesterone

52. For women with a singleton pregnancy who have had
a previous spontaneous singleton PTL
suggest
intramuscular injections of 17-alpha- hydroxyprogesterone caproate
rather than vaginal progesterone
(16 to 20 weeks) and continuing through the 36 th week
a previous spontaneous singleton PTL
intramuscular injections of 17-alpha- hydroxyprogesterone caproate

53. vaginal progesterone vaginal progesterone
cervical shortening (defined as ≤20 mm before 24 weeks) and no prior spontaneous singleton preterm birth,
suggest
vaginal progesterone
through the 36 th week.
vaginal suppository (100 or 200 mg),
gel (90 mg),
or tablet (100 mg micronized progesterone)
vaginal progesterone

54. Use of progesterone for indications other than is not supported
prior preterm birth
and short cervix

57. Progestational Agents to Prevent Preterm Birth. Progesterone
supplementation for women at risk for preterm birth was
investigated with regard to several plausible mechanisms of
action, including reduced gap junction formation and oxytocin
antagonism leading to relaxation of smooth muscle, maintenance
of cervical integrity, and anti-inflammatory effects.

58. Although the benefit of progesterone supplementation has
been observed in multiple research trials, the optimal clinical
protocols for progesterone have not yet been developed