Supplemental Progesterone

Supplemental Progesterone and Miscarriage

Supplemental progesterone reduces miscarriages 54% in women with unexplained recurrent miscarriage

One hundred and eighty women with a history of recurrent, unexplained miscarriage (mean 3.5 miscarriages) were randomized to receive oral dydrogesterone (a potent form of progesterone)(10 mg twice daily), intramuscular human chorionic gonadotrophin (hCG; 5000 IU every 4 days) or no additional treatment (controls). Treatment was started as soon as possible after confirmation of pregnancy and continued until the 12th gestational week. All women received standard supportive care. Miscarriages were significantly less common in the dydrogesterone group (13.4%) than in the control group (29%); there were no statistically significant differences between the hCG group and the control group. There were no differences between the groups with respect to pregnancy complications or congenital abnormalities.

http://www.ncbi.nlm.nih.gov/pubmed/16253504

Supplemental progesterone lowers miscarriage risk 62%; only effective in recurrent miscarriage

Fifteen trials are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen (supplemental progesterone) and placebo or no treatment groups and no statistically significant difference in the incidence of adverse effect in either mother or baby. In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (odds ratio 0.38). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment.

http://www2.cochrane.org/reviews/en/ab003511.html

Supplemental progesterone lowered miscarriage risk by 56% in women with threatened miscarriage

Women with vaginal bleeding up to week 16 of pregnancy were randomised to dydrogesterone (a potent form of progesterone)(40 mg stat followed by 10mg twice daily) or conservative management (control group). The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation. The success rate in the dydrogesterone group was statistically significantly higher than that in the control group (87.5% vs. 71.6%). Miscarriage occurred in 12.5% of women in the dydrogesterone group compared with 28.4% in the control group. There were no differences between the groups with regard to the incidence of Caesarean section, placenta praevia, antepartum hemorrhage, preterm labour (weeks 28-36), pregnancy-induced hypertension or low birth weight (<2500 g) babies. There were no intrauterine deaths or congenital abnormalities in either group. CONCLUSION: Compared with conservative management, dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage.

http://www.ncbi.nlm.nih.gov/pubmed/20005647

Supplemental progesterone lowered miscarriage risk by 30% in women with threatened miscarriage

Women who presented with mild or moderate vaginal bleeding during the first trimester of pregnancy were randomised to receive oral dydrogesterone (a potent form of progesterone)(10mg twice daily) or no treatment. Dydrogesterone was continued until 1 week after the bleeding had stopped. All women received standard supportive care.The incidence of miscarriage was significantly lower in the dydrogesterone group than in the untreated group (17.5% vs. 25%). There were no statistically significant differences between the groups with respect to pregnancy complications or congenital abnormalities.

http://www.ncbi.nlm.nih.gov/pubmed/20007011

Vaginal progesterone lowers miscarriage risk 24% in women with luteal phase defect

A study was carried out to compare two groups of patients suffering from recurrent miscarriage during the first trimester and luteal phase deficiency: one group underwent natural progesterone treatment in the form of a vaginal cream (ESOLUT) at a dose of 100 mg a day. The second group, formed a control group and did not receive any additional progestin treatment. A lower incidence of miscarriage during the first trimester was noted at the end of the study in treated patients compared to the control group (16% vs 21%).

http://www.ncbi.nlm.nih.gov/pubmed/11189968

Large review finds supplemental progesterone useful in recurrent miscarriage

A Cochrane review has shown a small but statistically significant difference in the live birth rate in the subgroup of women in which progestogen (supplemental progesterone) was used to prevent recurrent miscarriage.

http://www.ncbi.nlm.nih.gov/pubmed/15976551

Immune receptors lower in recurrent miscarriage; progesterone therapy restores them

Levels of soluble TNF-R1 and TNF-R2 in normal pregnancy were elevated when compared with non-pregnant normal women and pregnant recurrent miscarriage women. Levels of late activated CD8+ T-lymphocytes in normal pregnancy were decreased but no changes were detected in recurrent miscarriage women. After progesterone therapy (i.m. injections of 2.5% oil solution) in recurrent miscarriage women elevation of sTNF-R1 and sTNF-R2 to normal pregnancy ranges was observed. No changes in levels of late activated CD8+ T-lymphocytes after progesterone treatment were detected. CONCLUSIONS: Elevation of levels of sTNF-R1, sTNF-R2 and decrease of late activated cytotoxic T-lymphocytes are pronounce markers of normal human pregnancy. In recurrent miscarriage women there are no elevation of sTNF-R1 and sTNF-R2 levels during pregnancy. This deficiency may be restored by progesterone treatment.

http://www.ncbi.nlm.nih.gov/pubmed/16212650

Progesterone therapy is a safe and effective method for preventing miscarriage

Vaginal progesterone therapy was evaluated in women with a previous history of miscarriage or in women with infertility related to luteal phase defects. The results favor the benefit of using progesterone to diminish the risk of miscarriage. Other methods of stimulating progesterone production, e.g., human chorionic injections, are also effective. Progesterone therapy, especially when given vaginally, is effective with few side-effects and is safe. Thus the evidence suggests that one should err on the side of over-treatment rather than under-treatment in certain circumstances, e.g., advanced woman's age, previous history of miscarriage, or the use of follicle maturing drugs.

http://www.ncbi.nlm.nih.gov/pubmed/20101845

Early supplemental progesterone prevents implantation

After confirmation of the heat period, adult female mice were mated with mature healthy males to achieve pregnancy. Inseminated females received intraperitoneal injections of progesterone at doses of 0, 1, 3.5, 7, 15, 25, or 50 mg/kg body weight on the first, third, and seventh day of pregnancy (gestation in mice is 21 days). Pregnancy failure was evidenced by reduction in the number of embryos in females injected with 7 (25.12 %), 15 (38.44 %), 25 (100%), and 50 (100%) mg progesterone/kg body weight. In females with a successful pregnancy, the numbers of corpora lutea and postimplantation loss per dam were comparable across all groups. No increase in the incidence of malformed fetuses was found in any progesterone-treated groups. CONCLUSION: Administration of supranormal levels of progesterone during early pregnancy caused a reduction in the number of implantations and an increase in preimplantation loss in mice.

http://www.ncbi.nlm.nih.gov/pubmed/18692799

Safety of Supplemental Progesterone

Supplemental progesterone does not cause pregnancy complications

Intramuscular progesterone treatment due to threatened miscarriage during early pregnancy did not associate with a higher risk for pregnancy complications, preterm birth and low birth weight newborns.

http://www.ncbi.nlm.nih.gov/pubmed/20079582

No evidence that supplemental progesterone causes birth defects

Between 1977 and 2005, 28 cases of potential links between maternal dydrogesterone use during pregnancy and congenital birth defects were reported. The types of defects were very diverse, with no evidence of a pattern of abnormalities. The data do not provide evidence for congenital malformations associated with dydrogesterone use.

http://www.ncbi.nlm.nih.gov/pubmed/19193503

Supplemental progesterone does not appear to increase the risk of birth defects

Micronized progesterone, which is widely used in in vitro fertilization treatment, does not appear to increase the risk of congenital birth defects.

http://www.ncbi.nlm.nih.gov/pubmed/18519067

Progesterone at 20 times the normal level, but not 2 times, may cause neural tube defects

The first group was incubated without any operation. The second group was injected with physiological saline. The third and fourth groups were injected with two and twenty times more than physiologic doses of progesterone respectively. After 48 hours of incubation, all embryos were analyzed for the presence of neural tube defects under light microscopy. Results: None of the eggs in the first three groups showed neural tube defects, whereas 81.8% of the eggs in the fourth group showed neural tube defects. Our study showed that progesterone at levels twenty times more than its physiologic level might cause neural tube defects. Further studies are needed to explain the mechanisms of this teratogenic effect.

http://www.bioline.org.br/pdf?ni06052

Progesterone pill increases thrombophilia risk

Pill form of progesterone (actually a synthetic version such as Progesotogen) taken at 400 mg can cause increased fluid retention, which may result in epilepsy, migraine, asthma, cardiac or renal dysfunction. Blood clots that can result in strokes and heart attacks, which may lead to death or long-term disability, may develop; pulmonary embolus or breast cancer can also develop as a result of progesterone therapy. Progesterone is associated with an increased risk of thrombotic disorders such as thrombophlebitis, cerebrovascular disorders pulmonary embolism, and retinal thrombosis.Common adverse effects include cramps, abdominal pain, skeletal pain, perineal pain, headache, arthralgia, constipation, dyspareunia, nocturia, diarrhea, nausea, vomiting, breast enlargement, joint pain, flatulence, hot flushes, decreased libido, thirst, increased appetite, nervousness, drowsiness, excessive urination at night.

http://en.wikipedia.org/wiki/Progesterone