George Creasy | Population Council (original) (raw)

Papers by George Creasy

Research paper thumbnail of Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol

Contraception, 2016

Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vagi... more Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150 mcg Nestorone® (NES) and 15 mcg ethinyl estradiol (EE). Study design: A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Results: Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. Conclusion: NES/EE CVR for up to 13 cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Implications: Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.

Research paper thumbnail of A double-blind placebo-controlled trial of oxytocin receptor antagonist (Antocin) maintenance therapy in patients with preterm labor

American Journal of Obstetrics and Gynecology, 1997

Research paper thumbnail of 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 in Obstetrics & Gynecology, Sep 26, 2007

Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in w... more Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. Methods This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at ≤ 32 weeks. Results A cervical length < 28 mm was identified in 46 randomized women: 19 of 313 who received progesterone and 27 of 307 who received the placebo. Baseline characteristics of the two groups were similar. In women with a cervical length < 28 mm, the rate of preterm birth at ≤ 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo (0% vs. 29.6%, P = 0.014). With progesterone, there were fewer admissions into the neonatal intensive care unit (NICU; 15.8% vs. 51.9%, P = 0.016) and shorter NICU stays (1.1 vs. 16.5 days, P = 0.013). There was also a trend toward a decreased rate of neonatal respiratory distress syndrome (5.3% vs. 29.6%, P = 0.060).

Research paper thumbnail of Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations With a Short Cervix: A Meta-Analysis of Patient Data

Obstetric Anesthesia Digest, Dec 1, 2018

Disclosure: RR, AC-A, EDF, EC, SSH, and KHN declare no conflict of interest. JMO'B was involved i... more Disclosure: RR, AC-A, EDF, EC, SSH, and KHN declare no conflict of interest. JMO'B was involved in studies of progesterone gel treatment for preterm birth prevention sponsored by a maker of progesterone gel. He served on advisory boards and as a consultant for Watson Pharmaceuticals, a company with a financial interest in marketing vaginal progesterone gel for preterm birth prevention; he and others are listed in a patent on the use of progesterone compounds to prevent preterm birth (USA Patent Number 7884093: progesterone for the treatment and prevention of spontaneous preterm birth). He has received no royalty payments. GWC was an Employee of Columbia Laboratories, Inc. when the previous meta-analysis of individual patient data was conducted in 2011.

Research paper thumbnail of A double-blind placebo-controlled trial of an oxytocin-receptor antagonist (antocin) in the treatment of preterm labor

American Journal of Obstetrics and Gynecology, 1997

ABSTRACT OBJECTIVE: To evaluate the efficacy and safely of an oxytocin receptor antagonist (ANTOC... more ABSTRACT OBJECTIVE: To evaluate the efficacy and safely of an oxytocin receptor antagonist (ANTOCIN) in the treatment of preterm labor (PTL). STUDY DESIGN: 501 women with documented PTL (based on contractions and cervical findings) at 20-33 6/7 wks were randomized and received either ANTOCIN (n = 246) or placebo (n = 255). Subjects were to receive up to 48 hrs of IV study drug followed by a maintenance dose of 0.23 mL/hr via subcutaneous pump until 36 completed wks. Eligible subjects with recurrent PTL were treated with the assigned IV study medication. Primary outcome was number of days from start of study drug to either delivery or therapeutic failure (labor progression requiring use of alternate tocolytic [ALT]). Secondary outcomes included % of women who remained undelivered and did not receive an ALT at 24 hrs, 48 hrs, and 7 days. Maternal/fetal side effects and neonatal outcomes were also assessed. RESULTS: There was no significant difference between ANTOCIN (A) and placebo (P) for time to delivery or therapeutic failure (median of 25.6 days A vs. 21.0 days P). The % of subjects remaining undelivered and not requiring ALT after 24 hrs, 48 hrs, and 1 wk was significantly higher in the (A) group (Table). However, there was significant treatment by gestational age (GA) at admission interaction for each of these endpoints. ANTOCIN was superior to (P) for subjects randomized at GA ≥26.6 wks for the 7 day, at ≥27.3 wks for 48 hrs, and at ≥24.1 wks for 24 hr endpoints. 16 women in the (A) and 4 in the (P) were randomized at &lt;24 wks. Incidence of infant deaths was higher in this group among (A) subjects. Maternal/fetal adverse events were similar except for injection site reactions which occurred more often with (A). Undelivered and no Antocin Placebo Odds Ratio alternate locolytic at (n= 246) (n=255) (95% CI) 24 hours 179 (73%) 148 (58%) 1.93 (1.30-2.86) 48 hours 165 (67%) 142 (56%) 1.62 (1.11-2.37) 7 days 153 (62%) 125 (49%) 1.70 (1.17-2.46) CONCLUSION: ANTOCIN treatment of preterm labor is associated with a significantly higher percent of women who remained undelivered and not in need of ALT at 7 days. Benefit is dependent on GA at treatment. Findings suggest a role for oxytocin receptor antagonist in the treatment of PTL.

Research paper thumbnail of 91257926 Endometrial morphology in asymptomatic postmenopausal women

Research paper thumbnail of Pulsatile Delivery Systems

Annals of the New York Academy of Sciences, Feb 1, 1991

Research paper thumbnail of Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol

Contraception, 2016

Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vagi... more Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150 mcg Nestorone® (NES) and 15 mcg ethinyl estradiol (EE). Study design: A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Results: Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. Conclusion: NES/EE CVR for up to 13 cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Implications: Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.

Research paper thumbnail of Vaginal Progesterone Reduces the Rate of Preterm Birth in Women With a Sonographic Short Cervix: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Obstetrical & Gynecological Survey, 2011

Background: Women with a sonographic short cervix in the mid-trimester are at increased risk for ... more Background: Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods: This was a multicenter, randomized, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10 to 20 mm) at 19-23 6/7 weeks of gestation. Women were randomly allocated to receive vaginal progesterone gel or placebo daily from 20-23 6/7 weeks until 36 6/7 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. Findings: Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 3 weeks than those allocated to placebo (8.9% [n=21] vs 16.1% [n=36], relative risk [RR] 0.55, 95% confidence interval [CI] 0.33-0.92, p=0.02). The effect remained significant after adjustment for co-variables (adjusted RR 0.52, 95% CI 0.31-0.91, p= 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 (5.1% vs 10.3%, RR 0.50, 95% CI 0.25-0.97, p=0.04) and 35 weeks (14.5% vs 23.3% RR 0.62, 95% CI 0.42-0.92, p=0.02), respiratory distress syndrome (3.0% vs 7.6% RR 0.39, 95% CI 0.17-0.92, p=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5% RR 0.57, 95% CI 0.33-0.99, p=0.04), and birth weight <1500 g (6.4% [15/234] vs 13.6% [30/220], RR 0.47, 95% CI 0.26-0.85, p=0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Interpretation: The administration of vaginal progesterone gel to women with a sonographic short cervix in the midtrimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation, and improved neonatal outcomes.

Research paper thumbnail of Профилактика преждевременных родов. Многоцентровое рандомизированное двойное слепое плацебо-контролируемое исследование

Reproductive Endocrinology, 2011

15, 16 V. aStaKHoV 17 o. yuzKo 18 w. KinzleR 19 B. Dattel 20 H. SeHDeV 21 l.mazHeiKa 22 D. mancHu... more 15, 16 V. aStaKHoV 17 o. yuzKo 18 w. KinzleR 19 B. Dattel 20 H. SeHDeV 21 l.mazHeiKa 22 D. mancHulenKo 23 m.t. geRVaSi 24 l. SulliVan 25 a. conDe-aguDelo 1 J.a. PHilliPS 26 g.w. cReaSy 27 Многоцентровое рандомизированное двойное слепое плацебо-контролируемое исследование ПрОфИЛАкТИкА ПрЕжДЕВрЕМЕННЫх рОДОВ* Беременность и роды *Вагинальный прогестерон снижает частоту преждевременных родов у женщин с УЗИ признаками укороченной шейки матки.

Research paper thumbnail of Procedes de reduction du ldl cholesterol post-menopausique

L'invention concerne des procedes de reduction du LDL cholesterol chez des femmes post-menopa... more L'invention concerne des procedes de reduction du LDL cholesterol chez des femmes post-menopausiques consistant a administrer un schema specifique d'une composition d'÷strogenes et une composition d'un ÷strogene et de progestines combines pendant un cycle de 21 jours. L'invention concerne egalement un schema therapeutique de remplacement d'hormones presentant des caracteristiques du LDL comprenant des doses conjointes d'une composition d'÷estrogenes seule et d'une composition d'÷strogenes et de progestine combines pour un schema specifique en un cycle de 21 jours.

Research paper thumbnail of La Administración De Progesterona Por Vía Vaginal a Mujeres Con Acortamiento Del Cuello Uterino Asintomático Detectado Por Ecografía en El Segundo Trimestre Disminuye El Parto Pretérmino y La Morbilidad Neonatal: Revisión Sistemática y Metaanálisis De Datos De Pacientes Individuales

Romero, Roberto; Nicolaides, Kypros; Conde-Agudelo, Agustin; Tabor, Ann; O'Brien, John M.; Ce... more Romero, Roberto; Nicolaides, Kypros; Conde-Agudelo, Agustin; Tabor, Ann; O'Brien, John M.; Cetingoz, Elcin; Da Fonseca, Eduardo; Creasy, George W.; Klein, Katharina; Rode, Line; Soma-Pillay, Priya; Fusey, Shalini; Cam, Cetin; Alfirevic, Zarko; Hassan, Sonia S. LA ADMINISTRACION DE PROGESTERONA POR VIA VAGINAL A MUJERES CON ACORTAMIENTO DEL CUELLO UTERINO ASINTOMATICO DETECTADO POR ECOGRAFIA EN EL SEGUNDO TRIMESTRE DISMINUYE EL PARTO PRETERMINO Y LA MORBILIDAD NEONATAL: REVISION SISTEMATICA Y METAANALISIS DE DATOS DE PACIENTES INDIVIDUALES Revista del Hospital Materno Infantil Ramon Sarda, vol. 31, num. 4, 2012, pp. 146-171 Hospital Materno Infantil Ramon Sarda Buenos Aires, Argentina

Research paper thumbnail of Erratum: Placebo studies with Atosiban (Acta Obstetricia et Gynecologica Scandinavica (1997) 76 (33))

Research paper thumbnail of Original research article Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20

Research paper thumbnail of Results of a phase 1, randomized, placebo-controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel

PLOS ONE, 2022

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) dru... more HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n = 7) received single dose of PC-6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were s...

Research paper thumbnail of Progesterone for preventing preterm birth

A medicament for use in treating or preventing the onset of preterm labor and subsequent preterm ... more A medicament for use in treating or preventing the onset of preterm labor and subsequent preterm birth in a pregnant woman with a short cervix of 1.0 cm to 3.0 cm, wherein the medicament includes progesterone and is formulated to administer a dose of between 90 mg and 250 mg of progesterone in order to minimize the shortening of the cervix, and wherein the medicament is formulated for administration by vaginal or intravaginally.

Research paper thumbnail of A Drug-Drug Interaction Study to Evaluate the Effects of Strong CYP3A Induction on the Pharmacokinetics of Segesterone Acetate and Ethinyl Estradiol in a Contraceptive Vaginal System

Fertility and Sterility, 2021

Research paper thumbnail of Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials

The Lancet Global Health, 2019

Summary Background A ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles... more Summary Background A ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles) delivers an average of 0·15 mg segesterone acetate and 0·013 mg ethinylestradiol per day. We evaluated the efficacy of this contraceptive vaginal system and return to menses or pregnancy after use. Methods In two identically designed, multicentre, open-label, single-arm, phase 3 trials (one at 15 US academic and community sites and one at 12 US and international academic and community sites), participants followed a 21-days-in, 7-days-out segesterone acetate and ethinylestradiol contraceptive vaginal system schedule for up to 13 cycles. Participants were healthy, sexually active, non-pregnant, non-sterilised women aged 18–40 years. Women were cautioned that any removals during the 21 days of cyclic use should not exceed 2 h, and used daily paper diaries to record vaginal system use. Consistent with regulatory requirements for contraceptives, we calculated the Pearl Index for women aged 35 years and younger, excluding adjunctive contraception cycles, as the primary efficacy outcome measure. We also did intention-to-treat Kaplan-Meier life table analyses and followed up women who did not use hormonal contraceptives or desired pregnancy after study completion for 6 months for return to menses or pregnancy. The trials are registered with ClinicalTrials.gov, numbers NCT00455156 and NCT00263341. Findings Between Dec 19, 2006, and Oct 9, 2009, at the 15 US sites, and between Nov 1, 2006, and July 2, 2009, at the 12 US and international sites we enrolled 2278 women. Our overall efficacy analysis included 2265 participants (1130 in the US study and 1135 in the international study) and 1303 (57·5%) participants completed up to 13 cycles. The Pearl Index for the primary efficacy group was 2·98 (95% CI 2·13–4·06) per 100 woman-years, and was well within the range indicative of efficacy for a contraceptive under a woman's control. The Kaplan-Meier analysis revealed the contraceptive vaginal system was 97·5% effective, which provided further evidence of efficacy. Pregnancy occurrence was similar across cycles. All 290 follow-up participants reported return to menses or became pregnant (24 [63%] of 38 women who desired pregnancy) within 6 months. Interpretation The segesterone acetate and ethinylestradiol contraceptive vaginal system is an effective contraceptive for 13 consecutive cycles of use. This new product adds to the contraceptive method mix and the 1-year duration of use means that women do not need to return to the clinic or pharmacy for refills every few months. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, the US Agency for International Development, and the WHO Reproductive Health Research Department.

Research paper thumbnail of Effects of coadministration of vaginal miconazole nitrate on the pharmacokinetics andabsorption of the nestorone and ethinyl estradiol contraceptive vaginal ring

Fertility and Sterility, 2017

Research paper thumbnail of Efficacy, cycle control, compliance, and safety in users of a contraceptive patch

International Journal of Gynecology & Obstetrics, 2000

Research paper thumbnail of Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol

Contraception, 2016

Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vagi... more Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150 mcg Nestorone® (NES) and 15 mcg ethinyl estradiol (EE). Study design: A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Results: Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. Conclusion: NES/EE CVR for up to 13 cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Implications: Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.

Research paper thumbnail of A double-blind placebo-controlled trial of oxytocin receptor antagonist (Antocin) maintenance therapy in patients with preterm labor

American Journal of Obstetrics and Gynecology, 1997

Research paper thumbnail of 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 in Obstetrics & Gynecology, Sep 26, 2007

Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in w... more Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. Methods This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at ≤ 32 weeks. Results A cervical length < 28 mm was identified in 46 randomized women: 19 of 313 who received progesterone and 27 of 307 who received the placebo. Baseline characteristics of the two groups were similar. In women with a cervical length < 28 mm, the rate of preterm birth at ≤ 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo (0% vs. 29.6%, P = 0.014). With progesterone, there were fewer admissions into the neonatal intensive care unit (NICU; 15.8% vs. 51.9%, P = 0.016) and shorter NICU stays (1.1 vs. 16.5 days, P = 0.013). There was also a trend toward a decreased rate of neonatal respiratory distress syndrome (5.3% vs. 29.6%, P = 0.060).

Research paper thumbnail of Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations With a Short Cervix: A Meta-Analysis of Patient Data

Obstetric Anesthesia Digest, Dec 1, 2018

Disclosure: RR, AC-A, EDF, EC, SSH, and KHN declare no conflict of interest. JMO'B was involved i... more Disclosure: RR, AC-A, EDF, EC, SSH, and KHN declare no conflict of interest. JMO'B was involved in studies of progesterone gel treatment for preterm birth prevention sponsored by a maker of progesterone gel. He served on advisory boards and as a consultant for Watson Pharmaceuticals, a company with a financial interest in marketing vaginal progesterone gel for preterm birth prevention; he and others are listed in a patent on the use of progesterone compounds to prevent preterm birth (USA Patent Number 7884093: progesterone for the treatment and prevention of spontaneous preterm birth). He has received no royalty payments. GWC was an Employee of Columbia Laboratories, Inc. when the previous meta-analysis of individual patient data was conducted in 2011.

Research paper thumbnail of A double-blind placebo-controlled trial of an oxytocin-receptor antagonist (antocin) in the treatment of preterm labor

American Journal of Obstetrics and Gynecology, 1997

ABSTRACT OBJECTIVE: To evaluate the efficacy and safely of an oxytocin receptor antagonist (ANTOC... more ABSTRACT OBJECTIVE: To evaluate the efficacy and safely of an oxytocin receptor antagonist (ANTOCIN) in the treatment of preterm labor (PTL). STUDY DESIGN: 501 women with documented PTL (based on contractions and cervical findings) at 20-33 6/7 wks were randomized and received either ANTOCIN (n = 246) or placebo (n = 255). Subjects were to receive up to 48 hrs of IV study drug followed by a maintenance dose of 0.23 mL/hr via subcutaneous pump until 36 completed wks. Eligible subjects with recurrent PTL were treated with the assigned IV study medication. Primary outcome was number of days from start of study drug to either delivery or therapeutic failure (labor progression requiring use of alternate tocolytic [ALT]). Secondary outcomes included % of women who remained undelivered and did not receive an ALT at 24 hrs, 48 hrs, and 7 days. Maternal/fetal side effects and neonatal outcomes were also assessed. RESULTS: There was no significant difference between ANTOCIN (A) and placebo (P) for time to delivery or therapeutic failure (median of 25.6 days A vs. 21.0 days P). The % of subjects remaining undelivered and not requiring ALT after 24 hrs, 48 hrs, and 1 wk was significantly higher in the (A) group (Table). However, there was significant treatment by gestational age (GA) at admission interaction for each of these endpoints. ANTOCIN was superior to (P) for subjects randomized at GA ≥26.6 wks for the 7 day, at ≥27.3 wks for 48 hrs, and at ≥24.1 wks for 24 hr endpoints. 16 women in the (A) and 4 in the (P) were randomized at &lt;24 wks. Incidence of infant deaths was higher in this group among (A) subjects. Maternal/fetal adverse events were similar except for injection site reactions which occurred more often with (A). Undelivered and no Antocin Placebo Odds Ratio alternate locolytic at (n= 246) (n=255) (95% CI) 24 hours 179 (73%) 148 (58%) 1.93 (1.30-2.86) 48 hours 165 (67%) 142 (56%) 1.62 (1.11-2.37) 7 days 153 (62%) 125 (49%) 1.70 (1.17-2.46) CONCLUSION: ANTOCIN treatment of preterm labor is associated with a significantly higher percent of women who remained undelivered and not in need of ALT at 7 days. Benefit is dependent on GA at treatment. Findings suggest a role for oxytocin receptor antagonist in the treatment of PTL.

Research paper thumbnail of 91257926 Endometrial morphology in asymptomatic postmenopausal women

Research paper thumbnail of Pulsatile Delivery Systems

Annals of the New York Academy of Sciences, Feb 1, 1991

Research paper thumbnail of Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol

Contraception, 2016

Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vagi... more Objectives: Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150 mcg Nestorone® (NES) and 15 mcg ethinyl estradiol (EE). Study design: A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Results: Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. Conclusion: NES/EE CVR for up to 13 cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Implications: Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.

Research paper thumbnail of Vaginal Progesterone Reduces the Rate of Preterm Birth in Women With a Sonographic Short Cervix: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Obstetrical & Gynecological Survey, 2011

Background: Women with a sonographic short cervix in the mid-trimester are at increased risk for ... more Background: Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods: This was a multicenter, randomized, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10 to 20 mm) at 19-23 6/7 weeks of gestation. Women were randomly allocated to receive vaginal progesterone gel or placebo daily from 20-23 6/7 weeks until 36 6/7 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. Findings: Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 3 weeks than those allocated to placebo (8.9% [n=21] vs 16.1% [n=36], relative risk [RR] 0.55, 95% confidence interval [CI] 0.33-0.92, p=0.02). The effect remained significant after adjustment for co-variables (adjusted RR 0.52, 95% CI 0.31-0.91, p= 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 (5.1% vs 10.3%, RR 0.50, 95% CI 0.25-0.97, p=0.04) and 35 weeks (14.5% vs 23.3% RR 0.62, 95% CI 0.42-0.92, p=0.02), respiratory distress syndrome (3.0% vs 7.6% RR 0.39, 95% CI 0.17-0.92, p=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5% RR 0.57, 95% CI 0.33-0.99, p=0.04), and birth weight <1500 g (6.4% [15/234] vs 13.6% [30/220], RR 0.47, 95% CI 0.26-0.85, p=0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Interpretation: The administration of vaginal progesterone gel to women with a sonographic short cervix in the midtrimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation, and improved neonatal outcomes.

Research paper thumbnail of Профилактика преждевременных родов. Многоцентровое рандомизированное двойное слепое плацебо-контролируемое исследование

Reproductive Endocrinology, 2011

15, 16 V. aStaKHoV 17 o. yuzKo 18 w. KinzleR 19 B. Dattel 20 H. SeHDeV 21 l.mazHeiKa 22 D. mancHu... more 15, 16 V. aStaKHoV 17 o. yuzKo 18 w. KinzleR 19 B. Dattel 20 H. SeHDeV 21 l.mazHeiKa 22 D. mancHulenKo 23 m.t. geRVaSi 24 l. SulliVan 25 a. conDe-aguDelo 1 J.a. PHilliPS 26 g.w. cReaSy 27 Многоцентровое рандомизированное двойное слепое плацебо-контролируемое исследование ПрОфИЛАкТИкА ПрЕжДЕВрЕМЕННЫх рОДОВ* Беременность и роды *Вагинальный прогестерон снижает частоту преждевременных родов у женщин с УЗИ признаками укороченной шейки матки.

Research paper thumbnail of Procedes de reduction du ldl cholesterol post-menopausique

L'invention concerne des procedes de reduction du LDL cholesterol chez des femmes post-menopa... more L'invention concerne des procedes de reduction du LDL cholesterol chez des femmes post-menopausiques consistant a administrer un schema specifique d'une composition d'÷strogenes et une composition d'un ÷strogene et de progestines combines pendant un cycle de 21 jours. L'invention concerne egalement un schema therapeutique de remplacement d'hormones presentant des caracteristiques du LDL comprenant des doses conjointes d'une composition d'÷estrogenes seule et d'une composition d'÷strogenes et de progestine combines pour un schema specifique en un cycle de 21 jours.

Research paper thumbnail of La Administración De Progesterona Por Vía Vaginal a Mujeres Con Acortamiento Del Cuello Uterino Asintomático Detectado Por Ecografía en El Segundo Trimestre Disminuye El Parto Pretérmino y La Morbilidad Neonatal: Revisión Sistemática y Metaanálisis De Datos De Pacientes Individuales

Romero, Roberto; Nicolaides, Kypros; Conde-Agudelo, Agustin; Tabor, Ann; O'Brien, John M.; Ce... more Romero, Roberto; Nicolaides, Kypros; Conde-Agudelo, Agustin; Tabor, Ann; O'Brien, John M.; Cetingoz, Elcin; Da Fonseca, Eduardo; Creasy, George W.; Klein, Katharina; Rode, Line; Soma-Pillay, Priya; Fusey, Shalini; Cam, Cetin; Alfirevic, Zarko; Hassan, Sonia S. LA ADMINISTRACION DE PROGESTERONA POR VIA VAGINAL A MUJERES CON ACORTAMIENTO DEL CUELLO UTERINO ASINTOMATICO DETECTADO POR ECOGRAFIA EN EL SEGUNDO TRIMESTRE DISMINUYE EL PARTO PRETERMINO Y LA MORBILIDAD NEONATAL: REVISION SISTEMATICA Y METAANALISIS DE DATOS DE PACIENTES INDIVIDUALES Revista del Hospital Materno Infantil Ramon Sarda, vol. 31, num. 4, 2012, pp. 146-171 Hospital Materno Infantil Ramon Sarda Buenos Aires, Argentina

Research paper thumbnail of Erratum: Placebo studies with Atosiban (Acta Obstetricia et Gynecologica Scandinavica (1997) 76 (33))

Research paper thumbnail of Original research article Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20

Research paper thumbnail of Results of a phase 1, randomized, placebo-controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel

PLOS ONE, 2022

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) dru... more HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n = 7) received single dose of PC-6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were s...

Research paper thumbnail of Progesterone for preventing preterm birth

A medicament for use in treating or preventing the onset of preterm labor and subsequent preterm ... more A medicament for use in treating or preventing the onset of preterm labor and subsequent preterm birth in a pregnant woman with a short cervix of 1.0 cm to 3.0 cm, wherein the medicament includes progesterone and is formulated to administer a dose of between 90 mg and 250 mg of progesterone in order to minimize the shortening of the cervix, and wherein the medicament is formulated for administration by vaginal or intravaginally.

Research paper thumbnail of A Drug-Drug Interaction Study to Evaluate the Effects of Strong CYP3A Induction on the Pharmacokinetics of Segesterone Acetate and Ethinyl Estradiol in a Contraceptive Vaginal System

Fertility and Sterility, 2021

Research paper thumbnail of Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials

The Lancet Global Health, 2019

Summary Background A ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles... more Summary Background A ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles) delivers an average of 0·15 mg segesterone acetate and 0·013 mg ethinylestradiol per day. We evaluated the efficacy of this contraceptive vaginal system and return to menses or pregnancy after use. Methods In two identically designed, multicentre, open-label, single-arm, phase 3 trials (one at 15 US academic and community sites and one at 12 US and international academic and community sites), participants followed a 21-days-in, 7-days-out segesterone acetate and ethinylestradiol contraceptive vaginal system schedule for up to 13 cycles. Participants were healthy, sexually active, non-pregnant, non-sterilised women aged 18–40 years. Women were cautioned that any removals during the 21 days of cyclic use should not exceed 2 h, and used daily paper diaries to record vaginal system use. Consistent with regulatory requirements for contraceptives, we calculated the Pearl Index for women aged 35 years and younger, excluding adjunctive contraception cycles, as the primary efficacy outcome measure. We also did intention-to-treat Kaplan-Meier life table analyses and followed up women who did not use hormonal contraceptives or desired pregnancy after study completion for 6 months for return to menses or pregnancy. The trials are registered with ClinicalTrials.gov, numbers NCT00455156 and NCT00263341. Findings Between Dec 19, 2006, and Oct 9, 2009, at the 15 US sites, and between Nov 1, 2006, and July 2, 2009, at the 12 US and international sites we enrolled 2278 women. Our overall efficacy analysis included 2265 participants (1130 in the US study and 1135 in the international study) and 1303 (57·5%) participants completed up to 13 cycles. The Pearl Index for the primary efficacy group was 2·98 (95% CI 2·13–4·06) per 100 woman-years, and was well within the range indicative of efficacy for a contraceptive under a woman's control. The Kaplan-Meier analysis revealed the contraceptive vaginal system was 97·5% effective, which provided further evidence of efficacy. Pregnancy occurrence was similar across cycles. All 290 follow-up participants reported return to menses or became pregnant (24 [63%] of 38 women who desired pregnancy) within 6 months. Interpretation The segesterone acetate and ethinylestradiol contraceptive vaginal system is an effective contraceptive for 13 consecutive cycles of use. This new product adds to the contraceptive method mix and the 1-year duration of use means that women do not need to return to the clinic or pharmacy for refills every few months. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, the US Agency for International Development, and the WHO Reproductive Health Research Department.

Research paper thumbnail of Effects of coadministration of vaginal miconazole nitrate on the pharmacokinetics andabsorption of the nestorone and ethinyl estradiol contraceptive vaginal ring

Fertility and Sterility, 2017

Research paper thumbnail of Efficacy, cycle control, compliance, and safety in users of a contraceptive patch

International Journal of Gynecology & Obstetrics, 2000