1. Vaginal Progesterone In Women With An
Asymptomatic Sonographic Short Cervix In
The Midtrimester Decreases Preterm Delivery
And Neonatal Morbidity: A Systematic Review
And Meta-Analysis Of Individual Patient Data
Roberto Romero, MD, Kypros Nicolaides, etal.
American Journal of Obstetrics and
Gynecology (2011), doi: 10.1016/j.ajog.2011.12.003. The meta-
analysis is now available via open access at
http://www.ajog.org/article/S0002-9378(11)02358-1/abstract, and
will be published in the American Journal of Obstetrics and
Gynecology, the journal of the Society for Maternal-Fetal Medicine
(SMFM).

2. VAGINAL PROGESTERONE ( 8% GEL OR; 90-100 MG MICRONIZED CAPSULE
OR PROGESTERONE PESSARY) ONCE/DAILY FROM MIDTRIMRETSER
IDENTFICATION OF ASYMPTOMATIC CERCICAL SHORTENING < 25MM.
TRTEATMENT FROM IDENTIFICATION UNTIL 37 WEEKS, DECRESES PRETERM
BIRTH < 33 WEEKS BY 45 % AND DECREASES NEONATLAL MORBIDITY AND
MORTALITY
• Roberto Romero, M.D., Chief of the Perinatology Research Branch (PRB) of the Division of Intramural
Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) of the National Institutes of Health (NIH), was the Principal Investigator of the meta-analysis,
which evaluated the efficacy and safety of vaginal progesterone for the prevention of preterm birth and
neonatal morbidity and mortality in asymptomatic women with a sonographic short cervix (≤25 mm) in
the mid-trimester of pregnancy. This double-blind, placebo controlled study evaluated a total of 775
women and 827 infants. Women between the ages of 15 and 45 at more than 40 sites in 10 countries
were evaluated.
• Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth at
<33 weeks, <35 weeks and <28 weeks,
• COMPOSITE NEONATAL MORBIDITY AND MORTALITY was also significantly reduced specifically:
1. respiratory distress syndrome,
2. birth weight <1500 g, admission to NICU,
3. and requirement for mechanical ventilation.
• There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse
maternal events or congenital anomalies

3. Results not applicable to all patients
Trials were included if the primary aim of the study was to prevent preterm birth in
women with a short cervix, or if the primary aim was to prevent preterm birth
in women with risk factors other than a short cervix, but outcomes were
available for patients with a pre-randomization cervical length of 25 mm or less.
Trials were excluded if they:
1. Women with actual or threatened preterm labor, second trimester
bleeding or premature rupture of membranes were excluded;
2. evaluated the administration of vaginal progesterone in the first trimester only
to prevent miscarriage;
3. Of interest twins were included and demonstrated improved outcomes.
4. Of further interest women without a previous preterm delivery were included
also demonstrated improved outcome.
Although there is no agreement on what is a sonographic short cervix, we chose 25
mm as the cutoff because this value corresponds approximately to the 10th
percentile for cervical length in the midtrimester.10

4. SIGNIGIFICANT OUTCOMES
• Treatment with vaginal progesterone ONCE/DAY was associated with a
significant reduction in the rate of preterm birth
1. <28 weeks (RR 0.50, 95% CI 0.30-0.81)
2. <33 weeks (RR 0.58, 95% CI 0.42-0.80),
3. <35 weeks (RR 0.69, 95% CI 0.55-0.88)
• TREATMENT WITH VAGIANL PROGESETERONE WAS ALSO ASSOCAITED WITH A SIGNIFICANT
REDUCTION IN THE RATE OF COMPSOTIE NEONATAL MORBIDITY AND MORTALITY
• (RR 0.57, 95% CI 0.40-0.81)
• SPECFIC MEASURES OF MORBIDITY INCLUDED
1. respiratory distress syndrome (RR 0.48, 95% CI 0.30-0.76)
2. birth weight <1500 g (RR 0.55, 95% CI 0.38-0.80),
3. admission to NICU (RR 0.75, 95% CI 0.59-0.94),
4. and requirement for mechanical ventilation (RR 0.66, 95% CI 0.44-0.98).
• There were no significant differences between the vaginal progesterone and placebo groups in
the rate of adverse maternal events or congenital anomalies.

5. Reminiscent of McKenna 17P
PROPREITARY FORMULATION
RECOMMENDATIONS PENDING FROM SMFM / ACOG / NIH
SEVERAL OTHER PROGESTEREONE PRODUCTS WERE UTILIZED IN THE STUDY :(
8% VAGINAL GEL / 90-100 MILLIGRAMS VAGINAL CAPSULES / AND VAGINAL
PESSARIES/ AS WELL AS 200 MILLLIGRAMS VAGINAL TABLETS WITH NO
ADVANTAGE ATTRIBUTABLE TO EITHER PRODUCT OR DOSE
• Columbia Laboratories, Inc. is developing products that utilize its novel
bioadhesive drug delivery technologies to optimize drug delivery in a controlled,
sustained manner.
• The Company has developed and sold six products for the U.S. market including
CRINONE® (progesterone gel), for which Columbia receives royalties on annual net
sales from Watson Pharmaceuticals.
• CRINONE is commercialized outside the U.S. by Merck Serono.
• The Company’s New Drug Application (NDA) for progesterone vaginal gel 8% for
the reduction of risk of preterm birth in women with a singleton gestation and a
short uterine cervical length in the mid-trimester of pregnancy was accepted for
filing by the Food and Drug Administration (FDA) with a PDUFA date of February
26, 2012.
• The NDA is scheduled to be discussed by the Advisory Committee for
Reproductive Health Drugs of the FDA on January 20, 2012.

6. Proprietary 8% gel
PROCHIEVE®
• No obvious advantage demonstrated with outcomes
associated with the proprietary product except patient
convenience?? There in my opinion no controversy aas
what to use.
• PROCHIEVE® 8% (progesterone gel) is a bio adhesive
product that utilizes Columbia’s proprietary Bio adhesive
Delivery System (BDS) to deliver natural progesterone
vaginally in a convenient and patient-friendly, pre-filled,
tampon-like applicator.
• By using a non-immunogenic (hypo-allergenic) bio
adhesive polymer designed to adhere to the vaginal tissue,
PROCHIEVE 8% promotes controlled and sustained
absorption of progesterone and minimizes leakage, a side
effect commonly seen with vaginal suppositories.
• As a result, the product does not restrict normal activities.

7. UNTIL OFFICIAL
RECOMMENDATION
from SMFM / ACOG / NIH states otherwise
RIVERSIDE RECOMMENDATION
• FOR ASYMTOMATIC WOMEN NOTED TO HAVE
SHORT CERIX < 25 MM IN THE SECOND
TRIMESTER (INCLUDING TWINS AND PT WITH NO PREVIOUS ptd )
• TREAT WITH 90-100 milligrams
micronized vaginal suppository ONCE
DALY UNTIL 36 COMPLTED WEEKS