Hope these help some of you! Some of this we already know, but here's backup to convince docs.
Progesterone treatment to prevent preterm birth.
Meis PJ, Aleman A.
Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
The publication in 2003 of two large randomised trials of progesterone therapy to prevent preterm delivery has generated renewed interest in this treatment and has added substantial numbers of subjects to previously published small trials. The randomised trials of progestogens have generally shown efficacy in reducing the rate of recurrent preterm delivery in women with singleton pregnancies who were at high risk for preterm labour and delivery. Most of the successful trials have employed 17alpha-hydroxyprogesterone caproate, and one trial has reported positive results using progesterone vaginal suppositories.The administration of 17alpha-hydroxyprogesterone caproate or progesterone suppositories to women with these high-risk pregnancies showed a significant protective effect for preterm birth in six of the seven published trials. No successful trials of progestogens have been reported for women at risk for preterm delivery because of multiple gestations. Trials of progestogens after the occurrence of symptoms of labour have shown them to be ineffective in prolonging pregnancy.
PMID: 15482003 [PubMed - in process]
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1: Fertil Steril 2001 Jan;75(1):46-52
Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study.
Glueck CJ, Phillips H, Cameron D, Sieve-Smith L, Wang P.
The Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA.
glueckch@healthall.com
OBJECTIVE: To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS). DESIGN: Prospective pilot study. SETTING: Outpatient. PATIENT(S): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin. INTERVENTION(S): Metformin, 1.5-2.55 g/day, throughout pregnancy. MAIN OUTCOME MEASURE(S): Rates of first-trimester spontaneous abortion and teratogenicity. RESULT(S): Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (all > or = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04). CONCLUSION(S): Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.
Publication Types:
Clinical trial
PMID: 11163815 [PubMed - in process]
1: Fertil Steril 2000 Aug;74(2):394-7
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PCOS Miscarriage Cut to 12% With Metformin - Brief Article
ARLINGTON, VA. -- Metformin, a drug that allows women with polycystic ovary syndrome to ovulate normally and conceive, should be continued throughout their pregnancies because it also prevents miscarriage, Dr. Charles J. Glueck reported at the Clinical Research 2001 meeting.
Interim results of the ongoing study of 156 women with polycystic ovary syndrome (PCOS) who have received metformin throughout pregnancy showed 54 normal live births, 19 first-trimester miscarriages, 2 tubal pregnancies, and 81 ongoing pregnancies that appear normal on sonography at 13 weeks or more of gestation.
"So 87% have had a favorable outcome to date, and the rate of first-trimester miscarriage has been cut to 12%--which is about the national average in 'normal' women who have no endocrine disorders," commented Dr. Glueck of the cholesterol center at Jewish Hospital, in Cincinnati.
In fact, in a series of 183 pregnancies at his institution in which women with PCOS were not treated with metformin, the first-trimester miscarriage rate was a striking 64%, and the live birth rate was only 35%, he said at the meeting, sponsored by the American Federation for Medical Research.
Dr. Glueck speculated that the high miscarriage rate in PCOS is probably due to high levels of plasminogen activator inhibitor, which are markedly reduced by the metformin therapy. In untreated patients, these high levels can lead to thrombosis in the intervillus arteries and placental insufficiency or placental thrombus formation.
Dr. Glueck has also done "long-distance follow-up" on a separate group of 135 pregnancies in which the women were treated with metformin at his hospital to conceive then returned to their distant homes and their regular physicians for pregnancy management.
Physicians for 29 of these women stopped the metformin as soon as pregnancy was confirmed, and 6 of them (21%) had first-trimester miscarriages. In contrast, of the 106 women whose physicians continued metformin therapy throughout pregnancy only 13 (12%) have had a first-trimester miscarriage.
The drug has not produced any adverse effects on either the mother or fetus. "The overwhelming majority of the live births have occurred at 37 weeks or later," and the infants' weight and height distribution matches the national average almost exactly he noted.
Once metformin, an insulin-sensitizing agent, was found to induce normal menses and facilitate pregnancy in women with PCOS, attention turned to the outcome of those pregnancies.
In the question-and-answer session following his presentation, Dr. Glueck noted that metformin also may be preventing the development of gestational diabetes in these patients.
The average weight in the cohort of 156 women with PCOS was 226 pounds at conception, and most of the women were extremely insulin resistant. Yet the rate of gestational diabetes was only 4%. "Compare that with a rate of 58% seen in untreated women with PCOS, and it's clear that metformin drastically reduces gestational diabetes," he said.
The average weight gain in treated women was 11 pounds, and "many ended pregnancy thinner than when they started. In this patient population, that is a good thing," Dr. Glueck said.
When asked whether clinicians will soon be using metformin in women who develop gestational diabetes, Dr. Glueck answered that he considers it the drug of choice for such patients.
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Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.
da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M.
Obstetrics Clinic, University of Sao Paulo Medical School, Brazil.
riedu@uol.com.br
OBJECTIVE: The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population. STUDY DESIGN: A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test. RESULTS: The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05). CONCLUSION: Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.
Publication Types:
· Clinical Trial
· Randomized Controlled Trial
PMID: 12592250 [PubMed - indexed for MEDLINE]
American Journal of Obstetrics & Gynecology
Vol 190, Issue 6, June 2004
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In addition, the University of Alabama/Birmingham (through an NIH study) recommends a cerclage at 12 weeks and weekly 17P injections in women with history of PTL
NIH (in phase 3 now) has found the following results via vaginal progesterone gel (8% progesterone).
-placebo: 18.5% preterm birth
-progesterone: 2.7% preterm birth
Written up in the American Journal of Obstetrics and Gynecology
Vol 188, issue 2, Feb 2003, p 419-424 (see p. 303 of same issue)
Study ID: COL-1620-300
-a concurrent NIH study shows similar success with a 100 mg progesterone suppository/day
MC and PTL Research Studies 
