Clinical UM Guideline
|Subject:||Progesterone Therapy as a Technique to Prevent Preterm Delivery in High-Risk Women|
|Guideline #:||CG-DRUG-19||Current Effective Date:||11/17/2014|
|Status:||Revised||Last Review Date:||11/13/2014|
This document addresses the use of intramuscular injections of 17-alpha hydroxyprogesterone caproate or vaginal progesterone for the prevention of preterm birth in individuals at high-risk for preterm delivery.
Weekly injections of 17 alpha-hydroxyprogesterone caproate between 16 and 36 weeks of gestation are considered medically necessary in 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.
Daily vaginal progesterone suppositories between 24 and 34 weeks gestation are considered medically necessary in pregnant women with a prior history of preterm delivery before 37 weeks gestation.
Daily vaginal progesterone gel, when initiated between 20 and 23 weeks 6 days of gestation and continued until 36 weeks 6 days, is considered medically necessary for women with a singleton pregnancy with a prior history of a preterm delivery before 37 weeks gestation or a short cervix (measuring by ultrasound to be less than 20 mm).
Not Medically Necessary:
Progesterone therapy as a technique to prevent preterm labor is considered not medically necessary in other pregnant women who do not meet the above criteria, or those with other risk factors for preterm delivery, including, but not limited, to: multiple gestations, prior cervical cerclage, a uterine anomaly, positive tests for cervicovaginal fetal fibronectin or preterm labor within the current pregnancy.
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).
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.
|99506||Home visit for intramuscular injections|
|J1725||Injection, hydroxyprogesterone caproate, 1 mg [Makena]|
|J3490||Unclassified drugs [when specified as injectable 17-alpha hydroxyprogesterone caproate]|
|No specific code for progesterone suppositories|
|No specific code for vaginal gel [Crinone, Prochieve]|
|ICD-9 Diagnosis||[For dates of service prior to 10/01/2015]|
|649.70||Cervical shortening, unspecified as to episode of care [vaginal gel|
|649.73||Cervical shortening, antepartum condition or complication [vaginal gel]|
|V23.41-V23.49||Supervision of pregnancy with other poor obstetric history|
|ICD-10 Diagnosis||[For dates of service on or after 10/01/2015]|
|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]|
Preterm labor and delivery is a major determinant of neonatal morbidity and mortality; in the United States the rate of preterm birth is 12%. A variety of diagnostic and prophylactic measures have been investigated, including home uterine activity monitoring, subcutaneous terbutaline tocolytic therapy, and routine culture and antibiotic treatment of subclinical bacterial vaginosus. To date, none of the above has made a significant demonstrable impact on the incidence of preterm delivery. In the past, intramuscular injections of 17 alpha hydroxyprogesterone, (that is, Delalutin) were used routinely to prevent premature labor. However, the drug was shown to have teratogenic properties, and the FDA labeled the drug as Category D, (that is, studies have demonstrated fetal risk, but use of the drug may outweigh the potential risk). Delalutin is no longer marketed. Most recently, there has been renewed research interest in intramuscular injections of 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, when administered intramuscularly.
To date, 17P (17 alpha-hydroxyprogesterone caproate) has not been commercially available, but manufactured locally by compounding pharmacies. On February 3, 2011 K-V Pharmaceutical Company (St. Louis, MO) announced U.S. Food and Drug Administration (FDA) approval for Makena™ (formerly known as Gestiva™), subject to additional post-approval studies to be conducted regarding clinical outcomes benefit. Makena is the first synthetic progestin approved by the FDA and commercially available to reduce the risk of preterm birth. Makena was launched on March 14, 2011 and will be available through a limited distribution network. According to the FDA labeling, 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," (which is 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. To date, there are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.
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:
Regarding the continued availability of 17 alpha-hydroxyprogesterone caproate from compounding pharmacies, the FDA issued a statement on March 30, 2011, as follows:
The FDA understands that the manufacturer of Makena, KV Pharmaceuticals, has sent letters to pharmacists indicating that FDA will no longer exercise enforcement discretion with regard to compounded versions of Makena. This is not correct. In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products. As always, FDA may at any time revisit a decision to exercise enforcement discretion.
In 2012, the FDA issued an updated 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. Before approving the Makena NDA, the FDA reviewed manufacturing information, such as the source of the API used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice… FDA emphasizes that it is applying its normal enforcement policies for compounded drugs to compounded hydroxyprogesterone caproate. The compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding. As the Agency has previously explained, FDA generally prioritizes enforcement actions related to compounded drugs using a risk-based approach, giving the highest enforcement priority to pharmacies that compound products that are causing harm or that amount to health fraud.
This clinical guideline is largely based on an analysis of two randomized trials of progestational compounds, as a technique to prevent preterm delivery in high-risk women. Meis and colleagues focused on the use of weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate – 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. However, the following studies focused on the associated outcome of rates of preterm delivery, 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. Delivery prior to 34 weeks is more predictably associated with neonatal morbidity and mortality.
In the Meis study, 463 women with a history of a prior preterm delivery were randomized in a 2:1 ratio to receive either weekly intramuscular 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 preterm delivery 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 (%)
|Delivery before 37 weeks|
|Delivery before 35 weeks|
|Delivery before 32 weeks|
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 preterm delivery 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 preterm delivery rate in the control group would be 37%, based on the results of other studies. Therefore, the statistical significance of the difference in preterm delivery in the two groups may be related primarily to the unexpected high incidence of preterm delivery in the control group, rather than any treatment effect of 17P. The authors acknowledge the high incidence of preterm delivery 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 preterm delivery in the placebo group was 31 weeks ± 4.2 weeks. As noted by the authors, the risk of preterm delivery increases with a decreasing gestational age of the prior preterm delivery. However, the standard deviation of 4.2 weeks suggests that the study included subjects with a prior preterm delivery 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 preterm delivery 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 preterm delivery, and the lower rate in the intervention group, (which is similar to the anticipated rate), reflects a protective effect of 17P.
Prior randomized studies have also suggested that 17P is associated with a decreased incidence of preterm delivery. In a 1985 trial of 80 women considered at high risk, Yemini reported a preterm delivery rate of 37.8% in the control group, compared to 16.1% in the treated group (Yemini, 1985). A 1990 meta-analysis also supported the hypothesis that 17P does reduce the occurrence of preterm delivery (Keirse, 1990).
Da Fonseca and colleagues reported on the results of a trial that randomized 142 women considered at high risk for preterm delivery to receive either daily progesterone or placebo suppositories. While the Meis study included only women with a prior history of preterm delivery, this study included a broader range of subjects. Inclusion criteria included either a prior history of preterm birth, prophylactic cervical cerclage or a uterine malformation. Additionally, the mean gestational age of the prior preterm birth (33 weeks) was greater than the Meis trial, suggesting that, overall, this population of study subjects was at lower risk for preterm birth. The following pregnancy outcomes were reported:
|Delivery before 37 weeks|
|Delivery before 34 weeks|
As part of the design of the trial, the authors estimated that the overall incidence of preterm delivery was 25%, and therefore, the 28.5% incidence of preterm delivery in the placebo group was in the expected range, unlike the Meis trial (da Fonseca, 2003). In the da Fonseca (2003) randomized controlled trial, preterm birth occurred in 13.8% of the progesterone group and in 28.5% of the placebo group, which was statistically significant. Also in the placebo group, 18.5% of women delivered before 34 weeks, as compared with only 2.7% in the active treatment group (also significant). However, of the 142 high-risk subjects entered into this trial, only 4 subjects had an incompetent cervix requiring cerclage, and only 5 subjects 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. Since that time, no other published studies have focused specifically on the high-risk variables of either cervical cerclage or uterine anomaly. As a result, the current evidence supporting the effectiveness of progesterone in reducing preterm birth in women with either of these conditions remains insufficient.
Another systematic review also attempted to assess the benefits and harms of progesterone administration for the prevention of preterm birth in women and their infants. Eleven randomized controlled trials (2425 women and 3187 infants) were included. For women with a history of spontaneous preterm birth, progesterone was associated with a significant reduction in preterm birth before 34 weeks (one study, 142 women, relative risk [RR] 0.15, 95% confidence interval [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 preterm birth 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 preterm birth (Dodd, 2008).
A Cochrane meta-analysis review of progestogen therapy (the British word for progesterone) for prevention of miscarriage assessed 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 progestogen and placebo or no treatment groups (Peto odds ratio [Peto OR] 0.98; 95% CI 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby. Subgroup analysis of three 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 or no treatment (Peto OR 0.38; 95% CI 0.20 to 0.70). 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, 2008).
In November of 2003, the American College of Obstetrics and Gynecology (ACOG) issued a committee opinion on the use of progesterone to reduce preterm birth. This committee opinion reviewed the Meis and da Fonseca studies, discussed above. This document states:
(The results of these two studies) support the hypothesis that progesterone supplementation reduces preterm birth in a select very high-risk group. Despite the apparent benefits of progesterone in a high-risk population, the ideal progesterone formulation is unknown. The 17P used in the (Meis) trial was specially formulated for research and is not currently commercially available on a wide scale. Whether vaginal progesterone is equally efficacious remains to be proven in a larger population. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice believes that further studies are needed to evaluate the use of progesterone in those with other high-risk obstetric factors, such as multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. When progesterone is used, it is important to restrict its use to only women with a documented history of a previous spontaneous birth at less than 37 weeks of gestation, because unresolved issues remain, such as optimal route of drug delivery and long term safety of the drug.
In October 2008, ACOG issued an updated practice bulletin No. 419 on the use of progesterone for reduction of preterm birth which summarized the results of the clinical trials currently available and reaffirmed its view that:
Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and a prior spontaneous preterm birth due to spontaneous preterm labor or premature rupture of membranes. Current evidence does not support the routine use of progesterone in women with multiple gestations. Progesterone supplementation for asymptomatic women with an incidentally identified very short cervical length (less than 15 mm) may be considered; however, routine cervical length screening is not recommended…Recent studies support the hypothesis that progesterone supplementation reduces preterm birth in a select group of women. Despite the apparent benefits of progesterone, the ideal progesterone formulation is unknown…Based on current knowledge, it is important to offer progesterone for pregnancy prolongation to only women with a documented history of a previous spontaneous birth at less than 37 weeks of gestation. The ACOG Committee on Obstetric Practice and the Society for Maternal-Fetal Medicine (SMFM) believe that further studies are needed to evaluate the optimal preparation, dosage, route of administration, and other indications for the use of progesterone for the prevention of preterm delivery (ACOG, 2008; ACOG update, 2009).
In October 2012, ACOG issued an updated practice bulletin No. 130 entitled, Prediction and Prevention of Preterm Birth, which replaces the former Bulletin No. 419 (2008) described above. 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, an additional ACOG practice bulletin (No. 144) was issued on Multifetal Gestations that included the following statement on progesterone therapy:
In 2012, a clinical guideline was published by the SMFM, in which the following recommendations were made:
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 preterm birth 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 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 preterm birth 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 + 0 to 23 + 6 weeks of gestation were enrolled in this study. They were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth 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 preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) versus 16.1% (n=36); RR, 0.55; 95% CI: 0.33 to 0.92; p=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% versus 10.3%; RR, 0.50; 95% CI: 0.25 to 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 preterm birth before 33 weeks of gestation and with improved neonatal outcome (Hassan, 2011).
The Hassan trial results follow earlier studies, such as that reported by daFonseca regarding the use of vaginal progesterone in women at high risk of pre-term delivery 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 (between 24 and 34 weeks of gestation) vaginal progesterone or placebo capsules. Although vaginal progesterone therapy was associated with a reduction of 44% in the rate of preterm birth, questions remained regarding fetal outcomes; composite measures of neonatal therapy (25% vs. 33%) and morbidity (8% vs. 14%) which were not significantly reduced (daFonseca, 2007). Two additional publications of the same systematic reviews were published in 2009 which suggest that vaginal progesterone therapy may benefit a select group of women with short cervical length, and they advocate for routine screening of cervical length in the mid trimester, although this strategy is not currently recommended by the American College of Obstetrics and Gynecology (ACOG) (daFonseca, 2009a; daFonseca, 2009b). Additional recent evidence has been published regarding use of vaginal progesterone in at-risk pregnancies due to short cervix. 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 5 studies found that treatment with vaginal progesterone was associated with a statistically significant reduction in the risk of preterm birth before 33 weeks gestation, compared to placebo (12.4% vs. 22.0%, respectively; RR: 0.58, 95% CI: 0.42 to 0.80). When the analysis was limited to women with a singleton birth and no history of previous preterm birth, there remained a significant benefit of progesterone treatment to reduce the rate of preterm birth before 33 weeks (RR: 0.60, 95% CI: 0.39 to 0.92). The outcome of preterm birth before 36 weeks gestation was marginally significant, and there was not a significant difference between groups in the rate of preterm birth 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 preterm delivery, who were administered intravaginal progesterone gel (90 mg); results showed a significantly reduced rate of preterm birth (before 32 weeks) compared with placebo (DeFranco, 2007).
Gestation: This term refers to a pregnancy and is usually given to denote the status of the pregnancy in weeks relative to the time of conception.
Preterm birth: This term refers to a live birth before 37 completed weeks of gestation. Further definitions includes late preterm (34-36 weeks), moderately preterm (32-36 weeks) and very preterm (less than 32 weeks) (ACOG, 2009).
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 (ACOG, 2009).
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
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.
|Revised||11/13/2014||Medical Policy & Technology Assessment Committee (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. No change to clinical indications section. Discussion section and References were updated.|
|Reviewed||11/08/2012||MPTAC review. No change to position statements. Discussion section and References were updated.|
|Reviewed||11/17/2011||MPTAC review. No change to criteria. 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. No change to position statements or criteria. 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. No change to criteria. 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. No change to document criteria. 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.|
Last Review Date
|DRUG.00025||17-Alpha Hydroxyprogesterone Caproate for the Prevention of Preterm Delivery|
|WellPoint Health Networks, Inc.|
|8.09.02||Progesterone Therapy as a Technique to Prevent Preterm Delivery in High Risk Women|