Clinical UM Guideline

 

Subject: Progesterone Therapy as a Technique to Prevent Preterm Delivery in High-Risk Women
Guideline #:  CG-DRUG-19 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018

Description

 

This document addresses the use of intramuscular injections of 17-alpha hydroxyprogesterone caproate and vaginal progesterone for the prevention of preterm delivery in high-risk individuals.

 

Clinical Indications

Medically Necessary:

  1. Weekly injections of 17 alpha-hydroxyprogesterone caproate between 16 and 36 weeks of gestation are considered medically necessary in pregnant women who meet the following criteria:
    1. A singleton pregnancy; and
    2. Absence of preterm labor within the current pregnancy; and
    3. A prior history of a preterm delivery before 37 weeks gestation due to either of the following:
      1. Spontaneous preterm labor; or
      2. Premature rupture of membranes.
  2. Daily vaginal progesterone, when initiated between 16 and 24 weeks of gestation and continued until 36 weeks 6 days, is considered medically necessary for women with a singleton pregnancy and either of the following:
    1. A prior history of a preterm delivery before 37 weeks gestation; or
    2. A short cervix (measuring by ultrasound to be less than 20 mm).

Not Medically Necessary: 

  1. Progesterone therapy as a technique to prevent preterm labor is considered not medically necessary in pregnant women who do not meet the above criteria, or those with other risk factors for preterm delivery in the current pregnancy, including, but not limited, to: multiple gestation pregnancy, cervical cerclage, a uterine anomaly, positive tests for cervicovaginal fetal fibronectin or preterm labor.
  2. Injections of 17 alpha-hydroxyprogesterone caproate in a home setting by or through a licensed home health agency are considered not medically necessary, except when criteria for home health services are met (see CG-MED-23 Home Health).
Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT

 

99506

Home visit for intramuscular injections

 

 

HCPCS

 

J1726

Injection, hydroxyprogesterone caproate, (Makena), 10 mg

J1729

Injection, hydroxyprogesterone caproate, not otherwise specified, 10 mg

J7999

Compounded drug, not otherwise classified [when specified as a compounded progesterone product]

 

No specific code for progesterone suppositories

 

No specific code for vaginal gel [Crinone, Prochieve]

S9560

Home injectable therapy; hormonal therapy (e.g., Leuprolide, Goserelin), including administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment, per diem [when specified as progesterone therapy]

 

 

ICD-10 Diagnosis

 

O09.211-O09.219

Supervision of pregnancy with history of pre-term labor [includes codes O09.211, O09.212, O09.213, O09.219]

O09.291-O09.299

Supervision of pregnancy with other poor reproductive or obstetric history [includes codes O09.291, O09.292, O09.293, O09.299]

O26.872-O26.879

Other specified pregnancy related conditions, cervical shortening [vaginal gel]

Discussion/General Information

Preterm labor and delivery is a major cause of neonatal morbidity and mortality; in the United States the rate of preterm delivery (PTD) is 9.6% (Centers for Disease Control and Prevention [CDC], 2017).  In the past, intramuscular injections (IM) of 17 alpha-hydroxyprogesterone, (that is, Delalutin) were used to prevent the onset of premature labor.  However, the drug was subsequently found to have teratogenic properties, and the Food and Drug Administration (FDA) gave the drug a Category D pregnancy status meaning studies had demonstrated fetal risk, but use of the drug may outweigh the potential risk.  Delalutin is no longer on the market.  Research interest was renewed in a similar drug known as 17 alpha-hydroxyprogesterone caproate (17P) during the second trimester when the teratogenic risk is minimized.  17P is a weakly acting, naturally occurring, progesterone metabolite, which, when coupled with caproate dextran, works as a long-acting progestin.  17P is also administered by IM injection. 

On February 3, 2011, K-V Pharmaceutical Company (St. Louis, MO) announced approval of 17P, known as Makena® (formerly known as Gestiva).  Makena is the only synthetic progestin approved by the FDA and commercially available to reduce the risk of PTD.  According to the FDA label, Makena (hydroxyprogesterone caproate injection) is “A progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth” defined as delivery before 37 weeks of pregnancy.  The effectiveness of Makena is based on improvement in the proportion of women who delivered at less than 37 weeks of gestation.  

The FDA (2011) states:

Limitation of use: While there are many risk factors for preterm birth, the safety and efficacy of Makena has been demonstrated only in women with a prior spontaneous singleton preterm birth.  It is not intended for use in women with multiple gestations or other risk factors for preterm birth.  It is also not intended for use to stop active preterm labor.

Contraindications to use of Makena include:

In 2012, the FDA issued a statement regarding compounded versions of hydroxyprogesterone caproate (the active ingredient in Makena).  The FDA announced that it had completed its on-site review of compounded samples and summarized their findings as follows:

Although the analysis of this limited sample of compounded hydroxyprogesterone caproate products and active pharmaceutical ingredients (APIs) did not identify any major safety problems, approved drug products, such as Makena, provide a greater assurance of safety and effectiveness than do compounded products. 

This clinical guideline is largely based on an analysis of two randomized trials of progestational compounds, as a technique to prevent PTD in high-risk women.  Several follow-up confirmatory trials have been published and are also described here.  Meis and colleagues focused on the use of weekly IM injections of 17P (Meis, 2003), while da Fonseca and colleagues focused on the role of vaginal suppositories of progesterone (da Fonseca, 2003).  A variety of outcomes can be considered.  Ideally, a study would examine the outcomes of greatest clinical significance, such as perinatal morbidity, (as evidenced by days in the neonatal intensive care unit) or perinatal mortality.  The following studies focused on the associated outcome of rates of PTD, defined as birth prior to 37 weeks.  The limitation in this outcome is that as delivery approaches 37 weeks, the associated morbidity and mortality declines thus differences between treatment and non-treatment groups may be diminished by this single time-point for analysis.  Delivery prior to 34 weeks may be more predictably associated with neonatal morbidity and mortality.  

In the Meis study (FDA pivotal trial), 463 women with a history of a prior PTD were randomized in a 2:1 ratio to receive either weekly IM injections of 17P or a placebo injection, which consisted of castor oil (the same vehicle as used in the 17P injection).  Injections began at 16 to 20 weeks of gestation and continued until 36 weeks of gestation.  The primary outcome was PTD before 37 weeks of gestation, although delivery rates before 35 and 32 weeks were also reported.  These data are summarized in the table below:

Outcomes of Pregnancy

Intervention Group (%)

Placebo Group (%)

p value

Delivery before 37 weeks

36.3

54.9

< 0.001

Delivery before 35 weeks

20.6

30.7

0.02

Delivery before 32 weeks

11.4

19.6

0.02

The frequency of delivery before 37 weeks gestation was 36.3% in the progesterone group, as compared with 54.9% in the placebo group.  While this difference is statistically significant, it is important to note that the rate of PTD in the placebo group (54.9%) is exceptionally high.  For example, in calculating the required number of individuals needed to demonstrate a difference between the control and treatment group, (i.e., the power of the study), the investigators assumed that the PTD rate in the control group would be 37%, based on the results of other studies.  Therefore, the statistical significance of the difference in PTD in the two groups may be related primarily to the unexpected high incidence of PTD in the control group, rather than any treatment effect of 17P.  The authors acknowledge the high incidence of PTD in the control group and suggest that this rate may be related to the overall high risk in the enrolled participants.  For example, the mean gestational age of the prior PTD in the placebo group was 31 weeks ± 4.2 weeks.  As noted by the authors, the risk of PTD increases with a decreasing gestational age of the prior PTD.  However, the standard deviation of 4.2 weeks suggests that the study included subjects with a prior PTD at a gestational age of as low as 27 weeks ranging up to 35 weeks.  The distribution of the gestational ages is not provided.  At the very least, the high rate of PTD creates uncertainty as to whether the results of this study can be extrapolated to other populations (Greene, 2003).  Finally, as suggested in a letter to the editor (Brancazio, 2003), it is possible that the castor oil placebo somehow contributed to the high rate of PTD, and the lower rate in the intervention group, (which is similar to the anticipated rate), reflects a protective effect of 17P.

Several studies have investigated the effect of vaginal progesterone on the incidence of PTD. da Fonseca and colleagues (2003) reported on the results of a trial that randomized 142 women considered at high risk for PTD to receive either daily vaginal progesterone or placebo suppositories.  This study included a broad range of subjects including women with a prior history of PTD, prophylactic cervical cerclage or a uterine malformation.  The mean gestational age of the prior PTD was 33 weeks.  The following pregnancy outcomes were reported:

Pregnancy outcome

Placebo (%)

Intervention (%)

p value

Delivery before 37 weeks

28.5

13.8

0.03

Delivery before 34 weeks

18.6

2.8

0.002

As part of the design of the trial, the authors estimated that the overall incidence of PTD was 25%, and therefore, the 28.5% incidence of PTD in the placebo group was in the expected range (da Fonseca, 2003).  PTD occurred in 13.8% of the progesterone group and in 28.5% of the placebo group, which was statistically significant (p<0.05).  Also in the placebo group, 18.5% of women delivered before 34 weeks, as compared with only 2.7% in the active treatment group (p<0.05).  However, of the 142 high-risk subjects entered into this trial, only 4 subjects had an incompetent cervix requiring cerclage, and only 5 women had a uterine malformation.  As a result, it is difficult to extrapolate the overall conclusion of efficacy for progesterone vaginal suppository therapy in these two small groups.

In 2007, da Fonseca and colleagues conducted a clinical trial investigating the use of vaginal progesterone in women at high risk of PTD due to short cervical length.  This study, which was sponsored by the Fetal Medicine Foundation, randomized 250 women with a cervical length of 15 mm or less to nightly vaginal progesterone or placebo capsules between 24 and 34 weeks of gestation.  Although vaginal progesterone therapy was associated with a reduction of 44% in the rate of PTD, questions remained regarding fetal outcomes; composite measures of neonatal therapy (25% vs. 33%) and morbidity (8% vs. 14%) were not significantly reduced.

In 2011, Hassan and colleagues published results of a Phase III multi-center, randomized, double-blind, placebo-controlled trial in which intravaginal progesterone (90 mg) was administered mid-trimester to reduce the risk of PTD and associated neonatal complications in women with a sonographic short cervix.  Asymptomatic women with a singleton pregnancy and a sonographic short cervix (10 to 20 mm) at 19 weeks to 23 weeks and 6 days of gestation were enrolled in this study.  They were allocated randomly to receive vaginal progesterone gel or placebo daily starting between 20 weeks and 23 weeks and 6 days continuing until 36 weeks and 6 days, rupture of membranes or delivery, whichever occurred first.  Randomization sequence was stratified by center and history of a previous PTD.  The primary endpoint was PTD before 33 weeks of gestation.  Analysis was by intention-to-treat.  Of 465 women randomized, 7 were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis.  Results showed that women allocated to receive vaginal progesterone had a lower rate of PTD before 33 weeks than did those allocated to placebo (8.9% [n=21] versus 16.1% [n=36]; relative risk [RR], 0.55; 95% confidence interval [CI], 0.33-0.92; p=0.02).  Vaginal progesterone was also associated with a significant reduction in the rate of PTD before 28 weeks (5.1% versus 10.3%; RR, 0.50; 95% CI, 0.25-0.97; p=0.04), as well as the incidence of other neonatal complications and markers of mortality and morbidity, (such as respiratory distress syndrome, birth weight less than 1500 g).  There were no differences in the incidence of treatment-related adverse events between the groups.  The authors concluded that administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of PTD before 33 weeks of gestation and with improved neonatal outcome (Hassan, 2011).

In 2012, Romero published a meta-analysis of individual data from five randomized controlled trials, in which vaginal progesterone was compared to placebo or no treatment in asymptomatic pregnant subjects with a sonographic short cervix (cervical length 25 mm or less) in the mid-trimester.  All of the studies were double-blinded and placebo-controlled.  The studies included data on a total of 775 women, 723 (93%) with singleton pregnancies and 52 (7%) with twin pregnancies.  A pooled analysis of data from the five studies found that treatment with vaginal progesterone was associated with a statistically significant reduction in the risk of PTD before 33 weeks gestation, compared to placebo (12.4% vs. 22.0%, respectively; RR, 0.58; 95% CI, 0.42-0.80).  When the analysis was limited to women with a singleton birth and no history of previous PTD, there remained a significant benefit of progesterone treatment to reduce the rate of PTD before 33 weeks (RR, 0.60; 95% CI, 0.39-0.92).  The outcome of PTD before 36 weeks gestation was marginally significant, and there was not a significant difference between groups in the rate of PTD before 37 weeks gestation (37% in the treatment group and 43% in the placebo group; Romero, 2012).  An additional prospective cohort study provided secondary analysis of a prior study (O’Brien, 2007) of women with a short cervix (less than 28 mm) and a history of early PTD, who were administered vaginal progesterone gel (90 mg); results showed a significantly reduced rate of PTD (before 32 weeks) compared with placebo (DeFranco, 2007).

A systematic review assessed the benefits and harms of progesterone administration for the prevention of PTD in women and their infants.  A total of 11 randomized controlled trials (2425 women and 3187 infants) were included.  For women with a history of spontaneous PTD, four studies were included; two used IM progesterone and two used vaginal progesterone.  In this subset of the analysis, progesterone was associated with a significant reduction in PTD before 34 weeks (one study, 142 women; RR, 0.15; 95% CI, 0.04-0.64, number needed to treat 7; 95% CI, 4-17), but no statistically significant differences were identified for the outcome of perinatal death.  For women with a short cervix identified on ultrasound, progesterone was not associated with a significant difference in perinatal death (one study, 274 participants; RR, 0.38; 95% CI, 0.10-1.40), but there was a significant reduction in PTD before 34 weeks (one study, 250 women; RR, 0.58; 95% CI, 0.38-0.87, number needed to treat 7; 95% CI, 4-25).  The authors concluded that progesterone is associated with some beneficial effects in pregnancy outcome for some women at increased risk of PTD (Dodd, 2008). 

A Cochrane meta-analysis review of progesterone therapy for prevention of miscarriage (that is, pregnancy loss prior to 20 weeks gestation) 15 trials (of 2118 women) that were included regardless of gravidity and number of previous miscarriages.  Results showed no statistically significant difference in the risk of miscarriage between progesterone and placebo groups (Peto odds ratio [OR], 0.98; 95% CI, 0.78-1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.  A subgroup analysis of four of these trials, involving women who had recurrent miscarriages (three or more consecutive miscarriages), showed a statistically significant decrease in miscarriage rate in the treatment group, compared to placebo (Peto OR, 0.39; 95% CI, 0.210-0.72).  The authors concluded, “…There seems to be evidence of benefit in women with a history of recurrent miscarriage.  Treatment for these women may be warranted…Larger trials are currently underway to inform treatment for this group of women.” (Haas, 2013).

A systematic review and meta-analysis of randomized controlled trials (n=680) evaluated the reduced risk of PTD in singletons with a history of PTD when progesterone was administered IM (weekly) versus vaginally (daily) starting at 16 weeks gestation.  In this analysis, women who had received progesterone vaginally had a significantly lower rate of spontaneous PTD before 34 weeks (17.5% vs 25.0%; RR 0.71, 95% CI 0.53 to 0.95) and before 32 weeks (8.9% vs 14.5%; RR 0.62, 95% CI 0.40 to 0.94) but no difference was found at 24, 28 or 37 weeks.  Vaginally administered progesterone also resulted in significantly less adverse drug reactions (7.1% vs 13.2%; RR 0.53, 95% CI 0.31 to 0.91) and was associated with a lower rate of neonatal intensive care unit admissions (18.7% vs 23.5%; RR 0.63, 95% CI 0.47 to 0.83) compared to IM preparations of progesterone.  Cervical length was not included in this analysis (Saccone, 2016).  Two small randomized controlled trials in 66 and 78 pregnant women found that IM administration of progesterone and daily vaginal progesterone exhibited similar efficacy in reducing the rate of PTD in women with a history of PTD (Bahghi, 2015; Elimian, 2016).  A much larger randomized controlled trial enrolled 304 asymptomatic pregnant women with a sonographically short cervix, and no other risk factors for PTB.  The outcomes of PTB and change in cervical length, were not statistically different between the two groups (Pirjani, 2017).

In 2016, a multi-center, randomized, double-blind, placebo-control, clinical trial was published by Norman and colleagues (2016) evaluating the efficacy of vaginal progesterone as prophylaxis for PTD in women at high risk for PTD.  Administration of progesterone commenced at 22-24 weeks of gestation and continued through week 34.  High risk for PTD was defined as a previous PTD at 34 weeks or earlier, a cervical length of 25mm or less and positive fetal fibronectin test in conjunction with other clinical risk factors for PTD (obstetrical history of prior PTD or pregnancy loss).  The primary outcomes were related to fetal and infant morbidity and mortality.  A total of 1,228 women were randomized to the placebo group (n=610) and the vaginal progesterone group (n=618).  The authors concluded that fetal and infant outcomes were not significantly different in the placebo group, relative to women who received daily vaginal progesterone.  Some limitations of the study include that the treatment time-frame was from 22-24 weeks and ended at 34 weeks rather than beginning at 16-20 weeks and continuing through the standard gestational length of 37 weeks for a full-term infant.  Finally, the definition of “at risk” for PTD precluded a useful comparison to the indications for progesterone prophylaxis seen elsewhere in peer-reviewed literature as does the fact that 34% of the progesterone group was not taking progesterone at least 80% of the time.

In 2012, a previously published clinical guideline was reaffirmed by the Society for Maternal Fetal Medicine (SMFM), in which the following recommendations were made:

Also in 2012, ACOG issued a practice bulletin No. 130 entitled, Prediction and Prevention of Preterm Birth.  The following recommendations were made regarding progesterone therapy:

Level A:  (based on good and consistent scientific evidence)

Level B:  (based on limited or inconsistent scientific evidence)

In 2014, a separate ACOG practice bulletin (No. 144) was issued on Multifetal Gestations that included the following statement on progesterone therapy:

In a secondary analysis published by de Oliveira (2016) of a double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone (200 mg) or placebo, progesterone was not found to be associated with the frequency of uterine contractions in twin pregnancies.  Combs (2016) and colleagues conducted a meta-analysis of RCTs and found that IM progesterone administered in triplet pregnancies (n=232 mothers) had no impact on the rate of PTD prior to 32 weeks when compared to placebo injections.  El-refaie (2016) conducted a randomized controlled, single-center study in which 250 asymptomatic women pregnant with twins and who had a sonographically identified short cervix (20-25 mm) were enrolled at 20-24 weeks gestation.  The women were randomly assigned to receive daily vaginal suppositories (n=125) or placebo (n=125).  The primary outcome of interest was PTD before 34 weeks and secondary outcomes included neonatal morbidity and mortality measures.  The author’s concluded that pregnancy was significantly lengthened (p=0.002) and neonatal morbidity and mortality (p<0.001) were significantly reduced in the progesterone suppository group.  The authors suggest the efficacy demonstrated in this trial may be due to the higher dose used in this trial, relative to other trials (400mg), and that all women enrolled were at increased risk for PTD, aside from the multi-fetal gestation, due to a shortened cervical length (20-25mm).

A meta-analysis was conducted to investigate the safety and efficacy of vaginal progesterone in the prevention of PTB in women who have a sonographically short cervix (cervical length ≤ 25 m) in the mid-trimester and are pregnant with twins (Romero, 2017). Two independent reviewers selected studies, assessed the risk of bias and extracted data. The primary outcome measure was PTB at < 33 weeks' gestation. A total of 303 women (159 received vaginal progesterone and 144 received placebo) and their 606 fetuses/infants from 6 RCTs. Investigators determined that administration of vaginal progesterone was associated with a statistically significant reduction in the risk of PTB at <33 weeks (31.4% vs 43.1%; RR=0.69; 95% CI, 0.51-0.93). Vaginal progesterone was also associated with a significant decrease in the risk of preterm birth at the following time points < 35, < 34, < 32 and < 30 weeks' gestation.  Furthermore, neonatal death (RR=0.53; 95% CI, 0.35-0.81), respiratory distress syndrome (RR=0.70; 95% CI, 0.56-0.89), composite neonatal morbidity and mortality (RR=0.61; 95% CI 0.34-0.98), use of mechanical ventilation (RR=0.54; 95% CI, 0.36-0.81) and birth weight < 1500 g (RR=0.53; 95% CI, 0.35-0.80.  No significant difference emerged in neurodevelopmental outcomes of the infants at 4-5 years of age between the vaginal progesterone and placebo groups.

To date, progesterone has not been proven to be an effective prophylaxis for PTD in women who have no risk factors, in multi-fetal pregnancies or in women who have already experienced premature rupture of membranes in the current pregnancy or are experiencing symptoms of threatened labor or miscarriage (Combs, 2015; Combs, 2016; de Oliveira, 2016; Dodd, 2018; El-refaie, 2016; Jarde, 2017; Langen, 2017; Quist, 2018; Saccone, 2015; Suhag, 2015; Wood, 2017).  There is also evidence to suggest that progesterone’s efficacy may wane in those with a BMI of greater than 25 kg/m2 and may increase the risk of gestational diabetes; additional trials investigating dosing dependent on individual characteristics and confirming safety may be warranted (Co, 2015; Heyborne, 2015; Nelson, 2016).  

According to Truven Health Analytics DrugPoints® compendia, progesterone gel formulations, which include crinone® (Watson Pharma, Inc., Parsippany, NJ), prochieve® (Actavis Pharma, U.S.A.) and other brand names, have a Class 2A recommendation for the off-label indication of prevention of PTD of newborn due to presence of a short cervix (Evidence level: Category B [evidence favors efficacy]).  This recommendation was largely based on the results of the previously described Phase III trial by Hassan and colleagues (2011).

Definitions

Gestation period: The time in which a fetus develops, beginning with fertilization and ending with birth (usually denoted in weeks).

Miscarriage: Spontaneous abortion of pregnancy prior to 20 weeks gestation.

Preterm birth: A birth before 37 completed weeks of gestation.  Further definitions include, moderately preterm (32 to < 37 weeks), very preterm (28 to < 32 weeks) and extremely preterm (< 28 weeks).

Spontaneous preterm birth: Unintentional, unplanned labor before 37 completed weeks of gestation. While the cause of spontaneous preterm birth is unknown, a history of spontaneous preterm birth is one of the strongest predictors for a preterm birth in a subsequent pregnancy.

Teratogenic: Able to disturb the development of an embryo or fetus; may cause a birth defect or pregnancy termination.

References

Peer Reviewed Publications:

  1. Ahn KH, Bae NY, Hong SC, et al. The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality. J Perinat Med. 2017; 45(1):11-20.
  2. Areia A, Fonseca E, Moura P. Progesterone use after successful treatment of threatened pre-term delivery. J Obstet Gynaecol. 2013; 33(7):678-681.
  3. Awwad J, Usta IM, Ghazeeri G, et al. A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity. BJOG. 2015; 122(1):71-79.
  4. Bafghi AS, Bahrami E, Sekhavat L. et al. Comparative study of vaginal versus intramuscular progesterone in the prevention of preterm delivery: a randomized clinical trial. Electron Physician. 2015; 7(6):1301-1309.
  5. Berghella V, Figueroa D, Szychowski JM, et al. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010; 202(4):351.e1-6.
  6. Brancazio LR, Murtha AP, Heine RP. Prevention of recurrent preterm delivery by 17 alpha- hydroxyprogesterone caproate. N Engl J Med. 2003; 349(11):1087-1088.
  7. Briery CM, Klauser CK, Martin RW, et al. The use of 17-hydroxy progesterone in women with arrested preterm labor: a randomized clinical trial. J Matern Fetal Neonatal Med. 2014; 27(18):1892-1896.
  8. Briery CM, Veillon EW, Klauser CK, et al. Women with preterm premature rupture of the membranes do not benefit from weekly progesterone. Am J Obstet Gynecol. 2011; 204(1):54.e1-5.
  9. Brizot ML, Hernandez W, Liao AW, et al. Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2015; 213(1):82.e1-9.
  10. Caritis SN, Rouse DJ, Peaceman AM, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Maternal-Fetal Medicine Units Network (MFMU). Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009; 113(2 Pt 1):285-292.
  11. Co AL, Walker HC, Hade EM, Iams JD. Relation of body mass index to frequency of recurrent preterm birth in women treated with 17-alpha hydroxyprogesterone caproate. Am J Obstet Gynecol. 2015; 213(2):233.e1-e5.
  12. Coleman S, Wallace L, Alexander J, Istwan N. Recurrent preterm birth in women treated with 17 α-hydroxyprogesterone caproate: the contribution of risk factors in the penultimate pregnancy. J Matern Fetal Neonatal Med. 2012; 25(7):1034-1038.
  13. Combs CA, Schuit E, Caritis SN, et al. 17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis. BJOG. 2016; 123(5):682-690.
  14. Combs CA, Garite TJ, Maurel K, et al. 17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2015; 213(3):364.e1-12.
  15. Conde-Agudelo A, Romero R, Da Fonseca E, et al. Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis. Am J Obstet Gynecol. 2018; 219(1):10-25.
  16. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003; 188(2):419-424.
  17. da Fonseca EB, Bittar RE, Damiao R, Zugaib M. Prematurity prevention: the role of progesterone. Curr Opin Obstet Gyn. 2009b; 21(2):142-147.
  18. da Fonseca EB, Celik E, Parra M, et al.; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007; 357(5):462-469.
  19. da Fonseca EB, Damiao R, Nicholaides K. Prevention of preterm birth based on short cervix: progesterone. Sem Perinatol. 2009a; 33(5):334-337.
  20. Daskalakis G, Zacharakis D, Theodora M, et al. Safety and efficacy of the cervical pessary combined with vaginal progesterone for the prevention of spontaneous preterm birth. J Perinat Med. 2018; 46(5):531-537.
  21. DeFranco EA, O'Brien JM, Adair CD, et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007; 30(5):697-705.
  22. Dodd JM, Crowther CA, McPhee AJ, et al. Progesterone after previous preterm birth for prevention of neonatal respiratory distress syndrome (PROGRESS): a randomised controlled trial. BMC Pregnancy Childbirth. 2009; 9:6.
  23. Elimian A, Smith K, Williams M, et al. A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent preterm birth. Int J Gynaecol Obstet. 2016; 134(2):169-172.
  24. El-refaie W, Abdelhafez MS, Badawy A. Vaginal progesterone for prevention of preterm labor in asymptomatic twin pregnancies with sonographic short cervix: a randomized clinical trial of efficacy and safety. Arch Gynecol Obstet. 2016; 293(1):61-67.
  25. Greene MF. Progesterone and preterm delivery - déjà vu all over again. N Engl J Med. 2003; 348(24):2453-2455.
  26. Grobman WA, Thom EA, Spong CY, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012; 207(5):390.e1-8.
  27. Hassan SS, Romero R, Vidyadhari D, et al. PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011; 38(1):18-31.
  28. Heyborne KD, Allshouse AA, Carey JC, et al. Does 17-alpha hydroxyprogesterone caproate prevent recurrent preterm birth in obese women? Am J Obstet Gynecol. 2015; 213(6):844.e1-6.
  29. Jarde A, Lutsiv O, Park CK, et al. Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis. BJOG. 2017; 124(8):1163-1173.
  30. Karbasian N, Sheikh M, Pirjani R, et al. Combined treatment with cervical pessary and vaginal progesterone for the prevention of preterm birth: A randomized clinical trial. J Obstet Gynaecol Res. 2016; 42(12):1673-1679.
  31. Langen ES, Sit A, Sherwin K, et al. A double-blind, randomized, placebo-controlled trial of 17 alpha-hydroxyprogesterone caproate in the management of preterm premature rupture of membranes. Am J Perinatol. 2018; 35(8):779-784.
  32. Lim AC, Schuit E, Bloemenkamp K, et al. 17α-hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: a randomized controlled trial. Obstet Gynecol. 2011; 118(3):513-520.
  33. Lim AC, Schuit E, Papatsonis D, et al. Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies. Ultrasound Obstet Gynecol. 2012; 40(4):426-430.
  34. Mackenzie R, Walker M, Armson A, et al. Progesterone for the prevention of preterm birth among women at increased risk: a systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2006; 194(5):1234-1242.
  35. Meis PJ, Klebanoff M, Dombrowski MP, et al. Does progesterone treatment influence risk factors for recurrent preterm delivery? National Institute of Child Health and Human Development. Rockville, MD. Obstet Gynecol. 2005; 106(3):557-561.
  36. Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. N Engl J Med. 2003; 348(24):2379-2385.
  37. Nelson DB, McIntire, McDonald J, et al. 17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study. Am J Obstet Gynecol. 2017; 216(6):600.e1-600.e9.
  38. Ning A, Vladutiu CJ, Dotters-Katz SK, et al. Gestational age at initiation of 17-alpha hydroxyprogesterone caproate and recurrent preterm birth. Am J Obstet Gynecol. 2017; 217(3): 371.e1-371.
  39. Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomized, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009; 373(9680):2034-2040.
  40. Norman JE, Marlow N, Messow CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016; 387(10033):2106-2116.
  41. Northen AT, Norman GS, Anderson K et al. National Institute of Child Health and Human Development (NICHD). Maternal-Fetal Medicine Units (MFMU) Network. National Institutes of Health (NIH). Bethesda, MD. Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo. Obstet Gynecol. 2007; 110(4):865-872.
  42. O'Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007; 30(5):687-696.
  43. O'Brien JM, Lewis DF. Progestins for the prevention of spontaneous preterm birth: review and implications of recent studies. J Reprod Med. 2009; 54(2):73-87.
  44. Oler E, Eke AC, Hesson A. Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery. Int J Gynaecol Obstet. 2017; 138(1):12-16.
  45. Petrini JR, Callaghan WM, Klebanoff M, et al. Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States. Obstet Gynecol. 2005; 105(2):267-272.
  46. Pirjani R, Heidari R, Rahimi-Foroushani A, et al. 17-alpha-hydroxyprogesterone caproate versus vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix: A randomized controlled trial. J Obstet Gynaecol Res. 2017; 43(1):57-64.
  47. Porter TF, Scott JR. Evidence-based care of recurrent miscarriage. Best Pract Res Clin Obstet Gynaecol. 2005; 19(1):85-101.
  48. Pustotina O. Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix. J Matern Fetal Neonatal Med. 2018; 31(14):1830-1838.
  49. Quist-Nelson J, Parker P, Mokhtari N, et al. Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials. Am J Obstet Gynecol. 2018 Mar 31. [Epub ahead of print].
  50. Rittenberg C, Sullivan S, Istwan N, et al. Clinical characteristics of women prescribed 17 alpha-hydroxyprogesterone caproate in the community setting. Am J Obstet Gynecol. 2007; 197(3):262.e1-4.
  51. Rode L, Klein K, Nicolaides KH, et al. Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet Gynecol. 2011; 38(3):272-280.
  52. Rode L, Langhoff-Roos J, Andersson C, et al. Systematic review of progesterone for the prevention of preterm birth in singleton pregnancies. Acta Obstet Gynecol Scand. 2009; 88(11):1180-1189.
  53. Romero R, Conde-Agudelo A, El-Refaie W, et al. Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data. Ultrasound Obstet Gynecol. 2017; 49(3):303-314.
  54. Romero R, Nicolaides KH, Conde-Agudelo A, et al. Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study. Ultrasound Obstet Gynecol. 2016; 48(3):308-317.
  55. Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012; 206(2):124.e1-19.
  56. Rouse DJ, Caritis SN, Peaceman AM, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007; 357(5):454-461.
  57. Rozenberg P, Chauveaud A, Deruelle P, et al. Groupe De Recherche En Obstétrique et Gynécologie. Prevention of preterm delivery after successful tocolysis in preterm labor by 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Am J Obstet Gynecol. 2012; 206(3):206.e1-9.
  58. Saccone G, Khalifeh A, Elimian A, et al. Vaginal progesterone compared to intramuscular 17-alpha-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: a systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017; 49(3):315-321.
  59. Saccone G, Suhag A, Berghella V. 17-alpha-hydroxyprogesterone caproate for maintenance tocolysis: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol. 2015; 213(1):16-22.
  60. Sanchez-Ramos L, Kaunitz AM, Delke I. Progestational agents to prevent preterm birth: a meta-analysis of randomized controlled trials. Obstet Gynecol. 2005; 105(2):273-279.
  61. Schuit E, Stock S, Rode L, et al. Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis. BJOG. 2015; 122(1):27-37.
  62. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med. 2007; 357(5):477-487.
  63. Snegovskikh V, Park JS, Norwitz ER. Endocrinology of parturition. Endocrinol Metab Clin N Am. 2006; 35(1):173-191, viii.
  64. Sotiriadis A, Papatheodorou S, Makrydimas G. Perinatal outcome in women treated with progesterone for the prevention of preterm birth: a meta-analysis. Ultrasound Obstet Gynecol. 2012; 40(3):257-266.
  65. Spong CY. National Institute of Child Health and Human Development (NICHD), Pregnancy and Perinatology Branch. National Institutes of Health (NIH). Bethesda, MD. Prediction and prevention of recurrent spontaneous preterm birth. Obstet Gynecol. 2007; 110(2 Pt 1):405-415.
  66. Spong CY, Meis PJ, Thom EA, et al. National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network. Progesterone for prevention of recurrent preterm birth:  impact of gestational age at previous delivery. Am J Obstet Gynecol. 2005; 193(3 Pt 2):1127-1131.
  67. Suhag A, Saccone G, Berghella V. Vaginal progesterone for maintenance tocolysis: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol. 2015 Oct;213(4):479-487.
  68. Thornton JG. Progesterone and preterm labor -- Still no definite answers. N Engl J Med. 2007; 357(5):499-501.
  69. Tan PC, King AS, Vallikkannu N, Omar SZ. Single dose 17 alpha-hydroxyprogesterone caproate in preterm labor: a randomized trial. Arch Gynecol Obstet. 2012; 285(3):585-590.
  70. Tita AT, Rouse DJ. Progesterone for preterm birth prevention: an evolving intervention. Am J Obstet Gynecol. 2009; 200(3):219-224.
  71. van Os MA, van der Ven AJ, Kleinrouweler CE, et al. Preventing preterm birth with progesterone in women with a short cervical length from a low-risk population: a multicenter double-blind placebo-controlled randomized trial. Am J Perinatol. 2015; 32(10):993-1000.
  72. Winer N, Bretelle F, Senat MV, et al. 17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2015; 212(4):485.e1-485.
  73. Wood S, Rabi Y, Tang S, et al.  Progesterone in women with arrested premature labor, a report of a randomized clinical trial and updated meta-analysis. BMC Pregnancy Childbirth. 2017; 17(1):258.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. Multifetal gestations: twin, triplet, and higher-order multifetal pregnancies. No. 144. 2014. Available at: http://www.guideline.gov/content.aspx?id=48025&search=multifetal+gestations%3a+twin%2c+triplet%2c+and+higher-order+multifetal+pregnancies. Accessed on August 16, 2018.
  2. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. Management of preterm labor. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. Number 43. Obstet Gynecol. 2003; 101(5 Pt 1):1039-1047.
  3. American College of Obstetricians and Gynecologists (ACOG) Committee Practice Bulletin No. 130. Prediction and prevention of preterm birth. Obstet Gynecol. 2012; 120(4):964-973.
  4. American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 419, 2008. Use of progesterone to prevent preterm birth. Obstet Gynecol. 2008; 112(4):963-965.
  5. Centers for Disease Control and Prevention (CDC). Birthweight and gestation. Last updated March 31, 2017. Available at: https://www.cdc.gov/nchs/fastats/birthweight.htm. Accessed on August 16, 2018. 
  6. Hydroxyprogesterone caproate Monograph. Lexicomp® Online, American Hospital Formulary Services® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised December 11, 2011. Accessed on August 16, 2018.
  7. Berghella V. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012; 206(5):376-386.
  8. Dodd JM, Grivell RM, OBrien CM, et al. Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy. Cochrane Database Syst Rev. 2017; 10:CD012024.
  9. Dodd JM, Flenady VJ, Cincotta R, Crowther CA. Progesterone for the prevention of preterm birth: a systematic review. Obstet Gynecol. 2008; 112(1):127-134.
  10. Dodd JM, Jones L, Flenady V, et al. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;(7):CD004947.
  11. Farine D, Mundle WR, Dodd J, et al. Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada. The use of progesterone for prevention of preterm birth. J Obstet Gynaecol Can. 2008; 30(1):67-77.
  12. Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database Syst Rev. 2013;(3):CD003511.
  13. Hydroxyprogesterone Caproate. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated July 26, 2018. Available at: http://www.micromedexsolutions.com. Accessed on August 16, 2018.
  14. Makena® [Product Information], Bloomington, IN. Baxter Pharmaceutical Solutions LLC; Updated on February 26, 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021945s012lbl.pdf. Accessed on August 16, 2018.
  15. Makena Monogrpah ® Online, American Hospital Formulary Service® (AHFS). Online, Hudson Ohio. Lexi-Comp., Inc. Last revised December 13, 2011. Accessed on September 19, 2017.
  16. Papatsonis D, Flenady V, Liley H. Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour. Cochrane Database Syst Rev. 2009;(2):CD005938.
  17. Progesterone. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated July 26, 2018. Available at: http://www.micromedexsolutions.com. Accessed on August 16, 2018.
  18. Su LL, Samuel M, Chong YS. Progestational agents for treating threatened or established preterm labor. Cochrane Database Syst Rev. 2014;(3):CD006770.
  19. United States Food and Drug Administration (FDA). Updated FDA Statement on Compounded Versions of hydroxyprogesterone caproate (the active ingredient in Makena). Updated June 18, 2012. Available at: https://www.specialtypharmacytimes.com/news/updated-fda-statement-on-compounded-versions-of-hydroxyprogesterone-caproate. Accessed on August 16, 2018.
  20. Wahabi HA, Fayed AA, Esmaeil SA, Bahkali KH. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018 Aug 7; 8:CD00594. [Epub ahead of print].
Websites for Additional Information
  1. National Institute of Child Health and Human Development. Preterm labor and birth: Research activities and scientific advances. Available at: https://www.nichd.nih.gov/health/topics/preterm. Accessed on August 16, 2018.
Index

17AHPC
Alpha Hydroxyprogesterone
Crinone®
Hydroxyprogesterone, 17a-
Hylutin®
Makena
Prochieve®
Prodrox

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

09/13/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion/General Information, References and Websites sections.

Revised

11/02/2017

MPTAC review. Updated header language from “Current Effective Date” to “Publish Date.” Revised criteria to include MN statement. Clarified NMN criteria. Updated Background/Overview and References Section.  Updated Coding section with 01/01/2018 HCPCS changes; removed codes J1725, Q9985, Q9986 deleted 12/31/2017, added codes J1726, J1729 effective 01/01/2018.

 

07/01/2017

Updated Coding section with 07/01/2017 HCPCS changes.

Reviewed

11/03/2016

MPTAC review. Updated formatting in Clinical Indications section. Updated Description, Background/Overview, Definition and References Sections.

Revised

11/05/2015

MPTAC review. Reformatted criteria and amended indications for vaginal progesterone. Updated Background/Overview and References sections. Updated Coding section to note 01/01/2016 HCPCS changes; also removed ICD-9 codes.

 

07/01/2015

Updated Coding section with 07/01/2015 HCPCS changes.

 

04/01/2015

Updated Coding section; added HCPCS code S9560.

Revised

11/13/2014

MPTAC review. The medically necessary criteria have been expanded to include use of daily progesterone vaginal gel when other criteria are met. The Coding, Discussion and References sections were updated.

Reviewed

11/14/2013

MPTAC review. Discussion section and References were updated.

Reviewed

11/08/2012

MPTAC review. Discussion section and References were updated.

Reviewed

11/17/2011

MPTAC review. References were updated. Updated Coding section with 01/01/2012 HCPCS changes; removed Q2042 deleted 12/31/2011.

Revised

05/19/2011

MPTAC review. The position statement for injectable 17 alpha-hydroxyprogesterone caproate was clarified to state that pregnant women with a singleton pregnancy with a prior history of a preterm delivery before 37 weeks gestation due to spontaneous preterm labor or premature rupture of membranes, and the absence of preterm labor within the current pregnancy are criteria for medical necessity (taken from the 2009 updated ACOG statement). The Discussion section and References were updated. Updated Coding section with 07/01/2011 HCPCS changes.

Reviewed

02/17/2011

MPTAC review. Information about the newly FDA approved drug, Makena, and updated 2009 ACOG information was added to the Discussion section. The Definitions and References were also updated.

Revised

11/18/2010

MPTAC review. The note on pg. 1 regarding home injections has been replaced with a new not medically necessary statement as follows: Injections of 17 alpha-hydroxyprogesterone caproate in a home setting by or through a licensed home health agency are not medically necessary, except when criteria for home health services are met. (See CG-MED-23 - Home Health.) References and Coding were updated.

Revised

02/25/2010

MPTAC review. The position statement regarding use of daily vaginal progesterone suppositories has been revised to no longer consider history of prior cervical cerclage or uterine anomaly as medically necessary indications for treatment. These indications are now considered not medically necessary. The Discussion section, References and coding were updated.

Reviewed

02/26/2009

MPTAC review. Singleton pregnancy was added to the medically necessary criteria for clarification consistent with the updated 2008 ACOG position paper. Removed the section on Place of Service. References were updated.

Reviewed

02/21/2008

MPTAC review. References were updated.

New

03/08/2007

MPTAC review. Initial guideline development. Transferred content from DRUG.00025 Progesterone Therapy as a Technique to Prevent Preterm Delivery in High-Risk Women to new clinical UM guideline. Not Medically Necessary indications in new guideline previously considered Investigational/Not Medically Necessary in prior document. Coding and References were updated.

Pre-Merger Organizations

Last Review Date

Document Number

Title

 

Anthem, Inc.

 

04/28/2004

DRUG.00025

17-Alpha Hydroxyprogesterone Caproate for the Prevention of Preterm Delivery

WellPoint Health Networks, Inc.

04/28/2004

8.09.02

Progesterone Therapy as a Technique to Prevent Preterm Delivery in High Risk Women