INTRAUTERINE INSTILLATION OF PROSTAGLANDIN F2d
IN EARLY PREGNANCY
James R. Jones, M.D., Gwen P. Gentile, M.D., Ekkehard K. Kenmann, M.D., and Alice A. Soriero, Ph.D. Gynecologic Endocrinology Section Department of Obstetrics and Gynecology State University of New York, Downstate Medical Center Brooklyn, New York 11203 ABSTRACT Intrauterine PGF2oc. (Emg) was administered for termination of early pregnancy in 14 healthy volunteers. Rith 11 complete _ abortions, the efficiency rate of this technique is below conventional methods. In addition, the incidence of infection was high occurring in 12 out of 14 subjects. Because of persistent bleeding, six patients underwent a dilatation and curettage. Other significant sSde effects included transient hypertension, pain, nausea and restlessness. In the patients with a comolete abortion, the mean plasma progesterone concentratfon fell 37% after 8 hours POSt PGFp( instillation-and 90% 14 days later. The mean plasma estradiol-17) fell 26% over the initial eight hour period and 75% over the next 14 days. INTRODUCTION
In 1973 Csapo et al (l) reported on the intrauterine instillation of prostaglandins ("Prostaglandin Impact") to effect early abortions. The apparently high efficiency and low problem rates observed were extremely promising in tens of a non-surgical approach to early termination of pregnancy. Subsequently, further co $ narts appeared from Mocsary and Csapo 11 tory and optimistic r Karim (3) and Ylikorkala et al VP . Csapo (5), in an excellent review of'"Prostaglandin Impact", suggested that the technics could be further simplified for paramedical or self-administration. In 1974, Lichtman et al (6) reported on the intratuerine instillation of 5 mg Prostaglandin F2o'(PGF20() to 20 pregnant women whose last menstrual periods were between 38 and 46 days previously. Surprisingly, 35% of these subjects had experienced severe adverse reactions and the overall abortion success rate was only 65%. Because of the apparent discrepancies of these reports we decided to perform this additional study of 'Prostaglandin impact". In addition, this clinical study of PGF2& provided US with the opportunity to continue investigations into the hormonal changes effected by prostaglandins.
PROSTAGLANDINS JUNE 1975
VOL. 9 NO. 6
881
PROSTAGLANDINS
STUDY POPULATION AND METHODS: The study population consisted of 14 healthy, pregnant women between the ages of 18 and 37 years whose last menstrual periods were between 38 and 48 days previously. Two of the subjects were pregnant for the first time and none had more than six pregnancies. The diagnosis of early pregnancy was confirmed in all subjects by a positive inssunologicpregnancy test (Gravindex, Ortho Diagnostics). All subjects were voluntarily applying for abortions at the Downstate Medical Center. Spceifically excluded were subjects with uterine anomalies and any history of cardiac, hepatic or renal disorders. Written "informed consents" were obtained and each subject was admitted to the Clinical Research Center * for the instillation of prostaglandin. After admission, each subject was given an intravenous dose of PGF 100 ,ug in 1 ml saline to test for latent asthma or other undesyrable side effects to the drug. If this test was negative, she was givenDemero1 75 mg, Compazine 10 mg., and atropine 0.04 mg intramuscularly prior to the PGF2d instillation. The prostaglandin was supplied in ampules of 6.71 mg of a thromethamine salt of PGF2d which was diluted to 2 ml with physiologic saline. The subjects were placed in dorsolithotomy position, the vagina was thoroughly cleansed with povidone iodine solution, and a #5 French polyethylene catheter was threaded through the cervical OS to the fundus. PGF2o< solution was then injected slowly over a 15-20 minute period into the endometrial cavity. The subjects were allowed bathroom priveleges after the instillation and no restrictions were placed on food intake. They were discharged from the hospital eight hours after instillation. Routine follow-up was scheduled for 2 weeks later but all subjects were instructed to return or contact the investigators upon noticing any untoward symptoms.
*
The study was supported in part, by Grant RR-318 from the Clinical Research Center Program of the Division of Research Resources, National Institutes of Health.
882
JUNE 1975
VOL. 9 NO. 6
PROSTAGLANDINS
During and followingthe instillationof PGF , all subjects were frequentlymonitored for alterationsin blor pressure,pulse rate, temperatureand vaginal bleeding. Subjectiveside effects were also noted. Twenty-fourhour urines were collected for radioinmrnoassay determinationsof hCG (7) on the day prior to and the day of PGF2d instillationand repeated at the time of the examinationtwo weeks Blood samples re drawn for radioimunoassay estimationsof if::; estradiol-178(IT and progesterone(g) before, eight hours after, and two weeks after PGF2d instillation. RESULTS: A.
Clinical (Table I)
There was no undesirablereaction of any subject to the intravenous dose of 1OOug PGF2o
IN EARLY PREGNANCY
James R. Jones, M.D., Gwen P. Gentile, M.D., Ekkehard K. Kenmann, M.D., and Alice A. Soriero, Ph.D. Gynecologic Endocrinology Section Department of Obstetrics and Gynecology State University of New York, Downstate Medical Center Brooklyn, New York 11203 ABSTRACT Intrauterine PGF2oc. (Emg) was administered for termination of early pregnancy in 14 healthy volunteers. Rith 11 complete _ abortions, the efficiency rate of this technique is below conventional methods. In addition, the incidence of infection was high occurring in 12 out of 14 subjects. Because of persistent bleeding, six patients underwent a dilatation and curettage. Other significant sSde effects included transient hypertension, pain, nausea and restlessness. In the patients with a comolete abortion, the mean plasma progesterone concentratfon fell 37% after 8 hours POSt PGFp( instillation-and 90% 14 days later. The mean plasma estradiol-17) fell 26% over the initial eight hour period and 75% over the next 14 days. INTRODUCTION
In 1973 Csapo et al (l) reported on the intrauterine instillation of prostaglandins ("Prostaglandin Impact") to effect early abortions. The apparently high efficiency and low problem rates observed were extremely promising in tens of a non-surgical approach to early termination of pregnancy. Subsequently, further co $ narts appeared from Mocsary and Csapo 11 tory and optimistic r Karim (3) and Ylikorkala et al VP . Csapo (5), in an excellent review of'"Prostaglandin Impact", suggested that the technics could be further simplified for paramedical or self-administration. In 1974, Lichtman et al (6) reported on the intratuerine instillation of 5 mg Prostaglandin F2o'(PGF20() to 20 pregnant women whose last menstrual periods were between 38 and 46 days previously. Surprisingly, 35% of these subjects had experienced severe adverse reactions and the overall abortion success rate was only 65%. Because of the apparent discrepancies of these reports we decided to perform this additional study of 'Prostaglandin impact". In addition, this clinical study of PGF2& provided US with the opportunity to continue investigations into the hormonal changes effected by prostaglandins.
PROSTAGLANDINS JUNE 1975
VOL. 9 NO. 6
881
PROSTAGLANDINS
STUDY POPULATION AND METHODS: The study population consisted of 14 healthy, pregnant women between the ages of 18 and 37 years whose last menstrual periods were between 38 and 48 days previously. Two of the subjects were pregnant for the first time and none had more than six pregnancies. The diagnosis of early pregnancy was confirmed in all subjects by a positive inssunologicpregnancy test (Gravindex, Ortho Diagnostics). All subjects were voluntarily applying for abortions at the Downstate Medical Center. Spceifically excluded were subjects with uterine anomalies and any history of cardiac, hepatic or renal disorders. Written "informed consents" were obtained and each subject was admitted to the Clinical Research Center * for the instillation of prostaglandin. After admission, each subject was given an intravenous dose of PGF 100 ,ug in 1 ml saline to test for latent asthma or other undesyrable side effects to the drug. If this test was negative, she was givenDemero1 75 mg, Compazine 10 mg., and atropine 0.04 mg intramuscularly prior to the PGF2d instillation. The prostaglandin was supplied in ampules of 6.71 mg of a thromethamine salt of PGF2d which was diluted to 2 ml with physiologic saline. The subjects were placed in dorsolithotomy position, the vagina was thoroughly cleansed with povidone iodine solution, and a #5 French polyethylene catheter was threaded through the cervical OS to the fundus. PGF2o< solution was then injected slowly over a 15-20 minute period into the endometrial cavity. The subjects were allowed bathroom priveleges after the instillation and no restrictions were placed on food intake. They were discharged from the hospital eight hours after instillation. Routine follow-up was scheduled for 2 weeks later but all subjects were instructed to return or contact the investigators upon noticing any untoward symptoms.
*
The study was supported in part, by Grant RR-318 from the Clinical Research Center Program of the Division of Research Resources, National Institutes of Health.
882
JUNE 1975
VOL. 9 NO. 6
PROSTAGLANDINS
During and followingthe instillationof PGF , all subjects were frequentlymonitored for alterationsin blor pressure,pulse rate, temperatureand vaginal bleeding. Subjectiveside effects were also noted. Twenty-fourhour urines were collected for radioinmrnoassay determinationsof hCG (7) on the day prior to and the day of PGF2d instillationand repeated at the time of the examinationtwo weeks Blood samples re drawn for radioimunoassay estimationsof if::; estradiol-178(IT and progesterone(g) before, eight hours after, and two weeks after PGF2d instillation. RESULTS: A.
Clinical (Table I)
There was no undesirablereaction of any subject to the intravenous dose of 1OOug PGF2o
