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For prevention of a recurrent preterm birth (PTB), intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC) weekly is recommended. Vaginal progesterone is preferred for women at risk for PTB due to a short cervical length, but may be useful in women with a prior PTB. However, there is no consensus about the optimal vaginal formulation or its efficacy as compared to 17 OHPC to prevent recurrent PTB. We randomised 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous PTB, of a singleton (>16 to <37 weeks of gestation) to receive the 200 mg vaginal progesterone effervescent tablet daily (Group A) or IM 17-OHPC, 250 mg weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate of <37 weeks was similar (20% in Group A and 20.8% in Group B, p =  .918). The PTB rate of <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar in the two groups. Two neonates in Group A and four neonates in Group B required NICU admission, one of whom (Group B) died due to prematurity. Twenty percent of women in Group A and 29.2% in Group B reported adverse effects from their respective study medications (p =  .408, NS). Thus, there did not appear to be a difference between vaginal progesterone and 17-OHPC when used for the prevention of a recurrent PTB. Impact statement What is already known on this subject? Progesterone administration is useful for prevention of a recurrent preterm birth (PTB) and these women are prescribed the intramuscular 17-α-hydroxy progesterone caproate (IM 17 OHPC), 250 mg, weekly. Some studies found that vaginal progesterone (once daily) is also beneficial in these women, but there is no consensus regarding its efficacy when compared to 17 OHPC, or its optimal formulation and dose. What do the results of this study add? In the present study, 100 women with a singleton pregnancy between 16 and 24 weeks of gestation and ≥ one prior spontaneous singleton PTB or mid-trimester abortion were randomised to receive 200 mg of vaginal progesterone effervescent tablet daily (Group A) or 250 mg IM 17-OHPC weekly (Group B) till 37 weeks of gestation or delivery. The spontaneous PTB rate <37 weeks was similar in the two groups (20% in Group A and 20.8% in Group B, p = .918). The PTB rate <34 weeks or <28 weeks were also comparable. The mean birth weight and other neonatal outcomes were similar. Twenty percent of women in Group A and 29.2% of women in Group B reported adverse effects from their respective study medications (p = .408, NS). Thus, there did not appear to be a difference between the vaginal progesterone effervescent tablet and 17-OHPC when used for the prevention of a recurrent PTB. What are the implications of these findings for clinical practice and/or further research? The vaginal progesterone effervescent tablet may be a suitable alternative to IM 17 OHPC to prevent recurrent PTB. Future studies should identify the most appropriate route (IM or vaginal) and vaginal progesterone formulation for PTB prevention in women at risk for a recurrent PTB and in women with a short cervical length.

Purpose: The purpose of this study was to evaluate the bioavailability of hydroxyprogesterone caproate (HPC) administered as a subcutaneous injection in the back of the upper arm using a prefilled autoinjector syringe with a 27-gauge needle compared with standard intramuscular injection in the gluteus maximus using a 21-gauge needle., Methods: Healthy postmenopausal women 50 to 75 years old were randomized in a parallel group design to receive a single SC injection of 1.1 mL (275-mg total dose) of preservative-free HPC administered using an autoinjector in the back of the upper arm or a single IM injection of 1 mL (250-mg total dose) of preservative-free HPC administered in the gluteus maximus. Blood samples were collected through 1008 hours (42 days) after injection. The primary measures were the C max , AUC 0-t , and AUC 0-∞ . Secondary measures were T max , k e , t ½ , and injection site reactions captured as a treatment-emergent adverse event., Findings: The pharmacokinetic population consisted of 90 individuals; 45 received subcutaneous administration and 45 received intramuscular administration. Geometric mean whole blood concentrations of HPC were comparable between administration regimens. Subcutaneous administration resulted in a higher geometric mean C max than intramuscular administration (7.88 vs 6.91 ng/mL), but median T max values were comparable (48.1 vs 49.7 hours). The least square geometric mean ratios for AUC 0-168) , AUC 0-t , and AUC 0-∞ were 102.89%, 110.25%, and 113.51%, respectively, with all 90% CIs within the 80.0% to 125.0% window that defined bioequivalence. The ratio for C max was 113.95% with a 90% CI of 91.94% to 141.23% but with substantial overlap of individual values between administration regimens. The geometric mean t ½ of HPC was 212 hours for the subcutaneous administration and 188 hours for the intramuscular administration. The most common treatment-emergent adverse event was injection site pain (subcutaneous, 37.3%; intramuscular, 8.2%), described as mild (85%) to moderate (15%)., Implications: Administration of HPC by SC injection of 1.1 mL (275 mg) via autoinjector is bioequivalent to IM injection of 1.0 mL (250 mg). ClinicalTrials.gov identifier: NCT02940522., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Preterm birth is the leading cause of neonatal morbidity and mortality in nonanomalous neonates in the United States. Women with a previous early spontaneous preterm birth are at highest risk for recurrence. Weekly intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent prematurity. Although current guidelines recommend 17-alpha hydroxyprogesterone caproate initiation between 16 and 20 weeks, in clinical practice, 17-alpha hydroxyprogesterone caproate is started across a spectrum of gestational ages., Objective: The objective of the study was to examine the relationship between the gestational age at 17-alpha hydroxyprogesterone caproate initiation and recurrent preterm birth among women with a prior spontaneous preterm birth 16-28 weeks' gestation., Study Design: This was a retrospective cohort study of women from a single tertiary care center, 2005-2016. All women with ≥1 singleton preterm births because of a spontaneous onset of contractions, preterm prelabor rupture of membranes, or painless cervical dilation between 16 and 28 weeks followed by a subsequent singleton pregnancy treated with 17-alpha hydroxyprogesterone caproate were included. Women were grouped based on quartiles of gestational age of 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 14 0/7 to 16 1/7 ; quartile 2, 16 2/7 to 17 0/7 ; quartile 3, 17 1/7 to 18 6/7 ; and quartile 4, 19 0/7 to 27 5/7 ). Women with a gestational age of 17-alpha hydroxyprogesterone caproate initiation in quartiles 1 and 2 were considered to have early-start 17-alpha hydroxyprogesterone caproate; those in quartiles 3 and 4 were considered to have late-start 17-alpha hydroxyprogesterone caproate. The primary outcome was recurrent preterm birth <37 weeks' gestation. Secondary outcomes included recurrent preterm birth <34 and <28 weeks' gestation and composite major neonatal morbidity (diagnosis of grade III or IV intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis stage II or III, or death). Gestational age at delivery was compared by quartile of 17-alpha hydroxyprogesterone caproate initiation using Kaplan-Meier survival curves and the log-rank test. Logistic regression models estimated odds ratios for the association between gestational age at 17-alpha hydroxyprogesterone caproate initiation and preterm birth <37 weeks' gestation, adjusting for demographics, prior pregnancy and antenatal characteristics., Results: A total of 132 women met inclusion criteria; 52 (39.6%) experienced recurrent preterm birth <37 weeks in the studied pregnancy. 17-Alpha hydroxyprogesterone caproate was initiated at a mean 17 6/7 ± 2.5 weeks. Demographic and baseline characteristics were similar between women with early-start 17-alpha hydroxyprogesterone caproate (quartiles 1 and 2) compared with those with late-start 17-alpha hydroxyprogesterone caproate (quartiles 3 and 4). Women with early-start 17-alpha hydroxyprogesterone caproate trended toward lower rates of recurrent preterm birth <37 weeks compared with those with late-start 17-alpha hydroxyprogesterone caproate (41.3% vs 57.7%, P = .065). Delivery gestational age was inversely proportional to gestational age at 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 37 4/7 weeks vs quartile 2, 36 5/7 vs quartile 3, 36 1/7 weeks vs quartile 4, 34 0/7 , P = .007). In Kaplan-Meier survival analyses, these differences in delivery gestational age by 17-alpha hydroxyprogesterone caproate initiation quartile persisted across pregnancy (log-rank P < .001). In regression models, later initiation of 17-alpha hydroxyprogesterone caproate was significantly associated with increased odds of preterm birth <37 weeks. Women with early 17-alpha hydroxyprogesterone caproate initiation also had lower rates of major neonatal morbidity than those with later 17-alpha hydroxyprogesterone caproate initiation (1.5% vs 14.3%, P = .005)., Conclusion: Rates of recurrent preterm birth among women with a prior spontaneous preterm birth 16-28 weeks are high. Women beginning 17-alpha hydroxyprogesterone caproate early deliver later and have improved neonatal outcomes. Clinicians should make every effort to facilitate 17-alpha hydroxyprogesterone caproate initiation at 16 weeks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone., Study Design: Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve ® (also known as Crinone ® ), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied., Results: Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve ® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery., Conclusions: Prochieve ® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration., (Copyright © 2017. Published by Elsevier B.V.)

Background: Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed., Objectives: To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD., Search Strategy: Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery., Selection Criteria: Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included., Data Collection and Analysis: Study data were extracted and meta-analyses were performed when outcomes were comparable., Main Results: The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone., Conclusions: Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior., (© 2017 International Federation of Gynecology and Obstetrics.)

Background: The safety of preventive progestogen therapy for preterm birth remains to be established. This meta-analysis aimed to evaluate the effects of preventive progestogen therapy on neonatal mortality., Methods: Randomized controlled trials (RCTs) on the preventive use of progestogen therapy, published between October 1971 and November 2015, were identified by searching MEDLINE/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Library databases, CINAHL, POPLINE, and LILACS using "progesterone" and "preterm birth" as key terms. We conducted separate analyses according to the type of progestogen administered and plurality of the pregnancy., Results: Twenty-two RCTs provided data on 11,188 neonates. Preventive progestogen treatment in women with a history of preterm birth or short cervical length was not associated with increased risk of neonatal death compared to placebo in all analyzed progestogen types and pregnancy conditions. The pooled relative risks (95% confidence interval) of neonatal mortality were 0.69 (0.31-1.54) for vaginal progestogen in singleton pregnancies, 0.6 (0.33-1.09) for intramuscular progestogen in singleton pregnancies, 0.96 (0.51-1.8) for vaginal progestogen in multiple pregnancies, and 0.96 (0.49-1.9) for intramuscular progestogen in multiple pregnancies., Conclusions: The results of this meta-analysis suggest that administration of preventive progestogen treatment to women at risk for preterm birth does not appear to negatively affect neonatal mortality in single or multiple pregnancies regardless of the route of administration.

Objective: To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone for prevention of recurrent preterm birth., Methods: A prospective randomized controlled trial was conducted at a US tertiary care center between June 1, 2007, and April 30, 2010. Women with singleton pregnancies (16-20 weeks) and a history of spontaneous preterm birth were randomly allocated using a computer-generated randomization sequence to receive either a weekly intramuscular injection of hydroxyprogesterone caproate (250 mg) or a daily vaginal progesterone suppository (100 mg). Participants, investigators, and assessors were not masked to group assignment. The primary outcome was birth before 37 weeks of pregnancy. Per-protocol analyses were performed: participants who completed follow-up were included., Results: Analyses included 66 women given intramuscular progesterone and 79 given vaginal progesterone. Delivery before 37 weeks was recorded among 29 (43.9%) women in the intramuscular progesterone group and 30 (37.9%) in the vaginal progesterone group (P=0.50)., Conclusion: Weekly intramuscular administration of hydroxyprogesterone caproate and daily vaginal administration of a progesterone suppository exhibited similar efficacy in reducing the rate of recurrent preterm birth. ClinicalTrials.gov: NCT00579553., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Recognition of preterm birth as the major underlying cause of infant mortality in the United States has placed responsibility for prevention in the hands of obstetrician-gynecologists. The advent of effective methods to identify and treat women with increased risk is a major advance that will alter the focus of prenatal care. Adoption of research findings into clinical practice, never an easy task, will be particularly challenging for efforts to reduce the risk of preterm birth. Historical risk factors for preterm birth are numerous and variably defined. Measurement of the length of the cervix with ultrasonography requires unique personnel and facilities. Care algorithms exist but lack the detailed information that comes with experience. This review offers perspective and detail to aid health care practitioners in developing a prematurity prevention strategy appropriate to their practice population.

Objective: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action., Study Design: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed., Results: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group., Conclusion: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objectives: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies., Methods: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model., Results: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21)., Conclusion: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17-OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To examine pregnancy outcomes of women receiving weekly compounded 17 α-hydroxyprogesterone caproate (17P) injections through a home nursing program compared with those reported in a multicenter trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Network., Methods: The study sample was comprised of patients receiving compounded 17P through a home nurse administration care management program. Included were women with current singleton gestation and prior spontaneous preterm birth (SPTB) initiating 17P between 16 and 20 weeks. Maternal characteristics and pregnancy outcomes were compared between study group and NICHD Network trial patients., Results: Women (n = 5493) received a mean of 16.9 ± 4.0 injections. Of the 92,700 injections, 98.4% were administered within the recommended 5- to 9-day interval. Recurrent SPTB occurred in 28.3%. The overall rate of SPTB at <37 weeks was similar for black and nonblack women (p = 0.592). Within black or nonblack groups, preterm birth rates at <37 weeks were similar regardless of gestational age at start of 17P (p = 0.894 and p = 0.374, respectively). These results were similar to those reported in the multicenter trial. Fetal and neonatal death occurred in 0.8% (46/5493). No significant difference was observed in rate of fetal or neonatal death by gestational age at initiation of 17P (p = 0.478)., Conclusion: Home nurse administration of compounded 17P is safe and effective., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: Male-to-female (MTF) transsexuals are treated with estrogen with and without progestin through a variety of routes. The aim of this study is to evaluate the arterial stiffness in MTF transsexuals undergoing hormonal treatment., Methods: We evaluated the arterial stiffness in 156 MTF transsexuals (22 untreated and 129 treated with estrogen only or plus progestin) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor., Results: MTF transsexuals treated with parenteral estrogen were significantly older than untreated MTF transsexuals. Hematocrit, uric acid and activated partial thromboplastin time in treated MTF transsexuals were significantly lower than in untreated MTF transsexuals. The level of high-density lipoprotein cholesterol in MTF transsexuals treated with oral estrogen was significantly higher than in untreated MTF transsexuals or those treated with parenteral estrogen with and without progestin. The systolic blood pressure in MTF transsexuals treated with estrogen only is significantly lower than that in untreated MTF transsexuals. The brachial-ankle pulse wave velocity was significantly decreased in MTF transsexuals treated with estrogen compared to that in untreated MTF transsexuals or in those treated with estrogen plus progestin. The carotid augmentation index in MTF transsexuals treated with oral estrogen was significantly lower than that in MTF transsexuals treated with parenteral estrogen or oral estrogen plus progestin., Conclusions: Estrogen treatment is likely to have some beneficial effects on lipid metabolism and vascular function in MTF transsexuals; however, progestin administered with estrogen may have adverse effects on arterial stiffness., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Despite the introduction of 17-alpha-hydroxyprogesterone caproate (17P), the national preterm birth (PTB) rate remains unchanged. Our objectives were to determine whether the overall rate of PTB has decreased and whether there has been a shift in the trends of prematurity at our institution since the initiation of 17P use. We performed a cross sectional study of the PTB rate and gestational age distribution at delivery (GA-del) at our institution over two, 2-year time periods: TP1 (pre 17P, 1 Jan 2004-31 Dec 2005) and TP2 (post 17P, 1 Jan 2008-31 Dec 2009). Statistical analyses included χ(2) tests for categorical data, t-tests for continuous data, and multivariable logistic regression to control for confounders. Overall (n = 15,421), there was no difference in the rate of PTB from TP1 to TP2 (16.65 vs 16.95%, p = 0.62). Among those with a history of prior PTB (n = 2,141), the mean preterm GA-del was 10 days later in TP2 than in TP1 (33.13 vs 31.64 weeks, p < 0.01) and significantly more preterm infants in TP2 delivered between 34-36 6/7 weeks than in TP1 (65.00 vs 45.63%, p < 0.01). The odds of a preterm infant delivering in the late preterm period was 2.3-fold higher in TP2 than TP1 (95% CI 1.49-3.54) after controlling for confounders. The significant shift in GA-del towards the late preterm period in TP2 may be due to the introduction of 17P use at our institution. Additional studies are needed to determine whether these trends persist on a nationwide level.

Objective: To evaluate the effect of a single 250-mg dose of 17 alpha-hydroxyprogesterone caproate (17-OHPC) intramuscularly as adjunct to nifedipine tocolysis in preterm labor., Method: Women diagnosed with threatened preterm labor between 22 and 35 weeks' gestation scheduled to receive nifedipine tocolysis and prophylactic antenatal corticosteroid were randomized to a single intramuscular injection of 250 mg of 17-OHPC or placebo saline in a double-blind fashion. Nifedipine tocolysis and corticosteroids were administered to all participants. Further management was otherwise carried out according to providers' discretion. Main outcome measures are delivery within 48 h and 7 days., Results: Data were analyzed for the 56 participants randomized to 17-OHPC and 56 randomized to placebo. Delivery rates within 48 h were 11/54 (20.4%) versus 15/56 (26.8%) RR 0.76 (95% CI 0.38-1.51) and within 7 days were 13/52 (25.0%) versus 19/54 (35.2%) RR 0.71 (95% CI 0.39-1.29) for 17-OHPC and placebo groups, respectively, and were similar. Recruitment to delivery interval, gestation at delivery, delivery rate before 34 weeks' and 37 weeks' gestation, and neonatal outcomes were also similar., Conclusion: The results indicated that adjunctive single-dose 17-OHPC in combination with nifedipine tocolysis for threatened preterm labor did not delay delivery.

Preterm birth is the leading cause of perinatal morbidity and mortality in otherwise healthy infants, and the rate of pregnancies complicated by a premature delivery continues to rise. Subsequently, attempts have been made to reduce this rate by using progesterone supplementation during pregnancy. 17alpha-Hydroxyprogesterone caproate (17P), a metabolite of progesterone, also has been used as supplementation during pregnancy to prevent preterm births. We report a case of iatrogenic autoimmune progesterone dermatitis (APD) in a pregnant woman who received 17P therapy. Due to the increased use of 17P, our case could represent an increasingly prevalent entity that dermatologists and obstetricians should recognize. In this article, we discuss our findings and provide a basic review of APD.

Objective: The purpose of this study was to define the pharmacokinetic parameters of 17-hydroxyprogesterone caproate (17-OHPC) in multifetal gestation., Study Design: Blood was obtained at 24-28 weeks' gestation and at 32-35 weeks gestation in 97 women with twin and 26 women with triplet gestation who were receiving 17-OHPC. Six of the women with twins had daily blood sampling for 7 days between 24 and 28 weeks' gestation, and pharmacokinetic parameters were estimated with the use of noncompartmental analysis. Modeling was applied to estimate the population parameters and to simulate various treatment scenarios., Results: The apparent half-life of 17-OHPC was 10 days. Body mass index significantly impacted 17-OHPC concentrations, but fetal number and parity did not. Apparent clearance was significantly greater in African American than in white women (P = .025)., Conclusion: This is the first pharmacokinetic analysis of 17-OHPC in pregnant women. Determination of half-life, covariates that affect plasma 17-OHPC concentrations, and the modeling of drug behavior provide insights into this drug's pharmacologic properties during multifetal pregnancy., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: Evaluation of an outpatient 17 α-hydroxyprogesterone caproate (17P) administration programme., Methods: A retrospective analysis of data collected from patients with a history of preterm birth (PTB) and current singleton gestation enrolled between 16.0 and 20.9 weeks' gestational age (GA) for weekly outpatient 17P administration and nursing assessment between 7/2004 and 12/2007 was conducted (n=3139)., Results: The population was mostly white (50.3%), 18-35 years old (77.7%), and married (67.0%). Median GA at 17P initiation and stop was 17.4 (16.0, 20.9) weeks and 35.1 (18.6, 37.4) weeks. Mean injections per patient were 16.5±4.9, at an interval of 7.2 days. Median GA at delivery was 37.3 (18.6, 44.0) weeks. Rate of recurrent spontaneous PTB was 29.8%, with 15.5% and 7.0% with PTB at <35 and <32 weeks., Conclusions: This represents the largest cohort reported to date of patients prescribed 17P therapy in clinical practice to prevent recurrent spontaneous PTB.

Objective: To compare preterm birth rate and neonatal outcome in twin gestations randomized to either 17 alpha-hydroxyprogesterone caproate (17P) or placebo., Materials and Methods: Women with twin gestations between 20-30 weeks were randomized to receive weekly injections of either 250 mg 17P injection (Group I), or placebo (Group II). Maternal and neonatal outcome data was recorded., Results: Thirty twin intrauterine pregnancies were randomized; 16 received 17P and 14 received placebo. Demographic data as well as past history and gestational age at randomization were equivalent between groups (P = 0.286-0.847). All patients in both groups were Medicaid recipients. The incidence of preterm labor (P = 0.980), and premature rupture of the membranes (P = 0.525) were the same between groups. Gestational age at delivery was also similar between 17P (33.9 weeks) versus placebo (33.1 weeks, P = 0.190) as was the incidence of preterm birth <35 weeks (44% vs 79%, P = 0.117). Infant weight (P = 0.641), Apgar score at 5 minutes (P = 0.338) as well as neonatal morbidity such as respiratory distress syndrome (P = 0.838), patent ductus arteriosus (P = 0.704), intraventricular hemorrhage (P = 0.851) and necrotizing enterocolitis (P = 0.946) showed no difference. Days spent in the NICU among 17P (18.4) versus placebo (17.3, P = 0.155), neonatal death (P = 0.359) and those infants discharged with neurologic handicap (P = 0.594) were not different between groups., Conclusion: Amongst this group of twin gestations weekly 17HP injections did not reduce the incidence of preterm birth or the complications associated with prematurity.

Objective: To assess whether 17 alpha-hydroxyprogesterone caproate reduces the rate of preterm birth in women carrying triplets., Methods: We performed this randomized, double-blinded, placebo-controlled trial in 14 centers. Healthy women with triplets were randomly assigned to weekly intramuscular injections of either 250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo, starting at 16-20 weeks and ending at delivery or 35 weeks of gestation. The primary study outcome was delivery or fetal loss before 35 weeks., Results: One hundred thirty-four women were assigned, 71 to 17 alpha-hydroxyprogesterone caproate and 63 to placebo; none were lost to follow-up. Baseline demographic data were similar in the two groups. The proportion of women experiencing the primary outcome (a composite of delivery or fetal loss before 35 0/7 weeks) was similar in the two treatment groups: 83% of pregnancies in the 17 alpha-hydroxyprogesterone caproate group and 84% in the placebo group, relative risk 1.0, 95% confidence interval 0.9-1.1. The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident regardless of the conception method or whether a gestational age cutoff for delivery was set at 32 or 28 weeks., Conclusion: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with triplet gestations., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00099164, Level of Evidence: I.

Background: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies., Methods/design: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length., Discussion: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies., Trial Registration: Current Controlled Trials ISRCTN40512715.

A survey of the literature shows that in studies employing standardized criteria to define the response to progestin therapy, an objective remission is achieved in about one-third of patients with endometrial and breast cancer, and it is much less frequent in ovarian malignancy. The response is seldom complete and it is mostly of a short duration. There is a tendency towards an increased response-rate with increased dosage of progestin, in both endometrial and breast carcinoma, while the route of administration appears to be of minor importance. The clinical benefit of adjuvant progestin therapy in endometrial cancer is unproven. Simultaneous therapy with progestin and cytotoxic drugs seems not to increase the survival figures obtainable by cytotoxic therapy alone. The antiestrogen tamoxifen has an established efficacy in all these malignancies. The spectra of tumors sensitive to tamoxifen and to progestin are not completely identical. The optimal combination of these drugs awaits results from prospective studies. Selection of patients for progestin therapy with a sufficient degree of accuracy is not feasible by use of clinical or histological parameters. On the other hand, estrogen receptor determination already has an established position in the clinical evaluation of the sensitivity of breast cancer to endocrine therapy. The assay of progestin receptors from endometrial carcinoma tissue also seems to give reliable information; correct prediction was observed in 86% when the receptor data from five studies with 105 progestin therapies were correlated with the treatment results.