Preterm Labor 

In 2011, Hassan, MD showed that vaginally administered Natural Progesterone can be used to prevent preterm early delivery in women with a short cervix that was found on ultrasound. The uterus is a muscular bag that opens on one end to the birth canal. The muscular uterus has a cervix that looks like a short elephant trunk. When this “elephant trunk” becomes shortened, then women have a higher risk of preterm delivery. Women with short cervixes at mid trimester as detected by using a trans vaginal ultrasound are at a higher risk for preterm birth. A normal gestation time is 40 weeks. Hassan, MD and her researchers found giving progesterone lowered the preterm birth rate before 33 weeks from 16.1% to 8.9%. This was a whopping 44.7% decrease in preterm birth.

Hassan used progesterone gel that contained glycerin, mineral oil, polycarbophil, carbomer 934P, hydrogenated palm oil glyceride, sorbic acid, purified water and may contain sodium hydroxide.

465 women from 19 weeks of gestation to almost 24 weeks of gestation were given transvaginal ultrasounds. Short cervixes predict preterm delivery.[1] Those that had short cervixes defined as 10-20 mm long were given either a vaginal progesterone gel or a placebo starting from 20 weeks to nearly 24 weeks in their pregnancy. The progesterone gel or placebo was given until nearly 37 weeks if delivery did not occur. Delivery at nearly 37 weeks was induced by rupture of membranes. They defined preterm as any delivery before 33 weeks of gestation.

Of the 465 women, 458 were followed. Women that used 90 mg/day of progesterone gel vaginally taken once daily in the morning. 235 women took the vaginal progesterone gel, and 223 women took a placebo. 72 of the women 16% of them had a history of previous preterm birth between 20 and 35 weeks of gestation. The women that received the progesterone gel has a lower rate of of preterm birth 8.9% (21 women) versus 16.1% (36 women).

Babies born to women that took the progesterone gel had a significantly lower risk of RDS (respiratory distress syndrome) 3.0% (7 women) versus 7.6% (17 women). If the baby is born too early the lungs have not developed a surfactant and the baby has difficulty breathing. The rate of morbidity and mortality for progesterone taking women was also significantly lower 7.7% (18 women) versus 13.5% (30 women). There was no increase in adverse events such as vaginal pruritus (itching), vaginal discharge, vaginal candidiasis or nausea.[2]

In summary, women with a short cervix given vaginal progesterone gel showed a big drop in preterm deliveries, large drop in respiratory distress syndrome in their babies, the same adverse effects, and no down side to taking progesterone. Progesterone is safe.

In 2007, Fonseca, MD also investigated the use of micronized progesterone pills in women with short cevixes. He reported that previous randomized trials of progesterone administration who previously delivered prematurely showed that progesterone use reduced the risk of premature delivery. Short cervical length 15mm or less measured at a median of 22 weeks of gestation (range of 20 to 25 weeks) was found in 413 out of 24,620 pregnant women. This was a preterm delivery risk.[3]

250 of the 413 women were given vaginal progesterone pills. The rest were given a placebo. Preterm delivery defined as delivery that happened before 34 weeks was considerably less in the progesterone group than in placebo group 19.2% vs 34.4%. He reported that that was a non significant reduction in infant morbidity and mortality 8.1% vs 13.8%. Fonseca, MD used micronized progesterone pills consisting of 2 pills of 100 mg each for a total of 200 mg/day taken at night. Each pill had micronized progesterone, sunflower oil, soya lecithin, gelatin, glycerol and titanium dioxide. Fonseca MD started the progesterone at 24 weeks and ended at 34 weeks.

However, a study by O’Brien, MD using 90 mg/day of progesterone gel in the vagina on women with a history of preterm birth showed no effect of progesterone to reduce the preterm birth. 659 pregnant women with a history of preterm labor enrolled in the study. Half were given a placebo and half were given the progesterone gel vaginally at 18 to 22 weeks of gestation. O’Brien showed no change in outcome to decrease the preterm birth at less than 32 weeks. [4] However, a follow up analysis using the same data of women showed that women in the same study with short cervical length of less than 28 mm at 18 to 22 weeks did have a significant rate of lowering of preterm birth. Out of the original 659 pregnant women, 46 of these women had a cervical length of less than 28 mm. 19 of 46 received progesterone, and 27 of the 46 did not receive progesterone. The mothers that received progesterone had 0% of their babies go to the neonatal intensive care unit. But the mothers that did not receive progesterone had 29.6% of their babies admitted to the neonatal intensive care unit. With progesterone the women with short cervixes totally avoided babies being put into the intensive neonatal care unit. Their babies had a smaller incidence of have respiratory distress syndrome of 5.3% vs 29.6%.[5]

Brizot, MD, PhD gave 200 mg/day of progesterone or a placebo to 390 twin pregnancies whose mothers had no history of preterm delivery. Women that had twin pregnancies were started on vaginal progesterone or placeboes from 18 weeks to almost 22 weeks of gestation. Anything less than 34 weeks was considered to be preterm delivery. Brizot, MD found no difference between the 189 women in the progesterone group and 191 in the placebo group in the mean gestational age. 18.5% of the women on progesterone gave birth at and 14.6% of the placebo group gave birth before 34 weeks. There was no difference between in the baby’s mobility and mortality 15.5% (progesterone group) vs 15.9% (placebo group).[6]

In 2013, according to ACOG and SMFM (American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine), babies do best when born at 39 weeks and 2 weeks after that. Anything before and after, babies tend to have a decrease in health.

A premature preterm baby that goes into the neonatal intensive care unit may cost as much as $50,000 to $100,000 to treat. But that is not the worst of it. Frequently, the baby will have long term cognitive and lung problems. There may be intracranial bleeding and permanent lung scarring issues. 1 in 8 Medicaid patients is a premature birth. On the average, a Medicaid premature baby costs $13,729 as compared to a normal delivery $1,498. The total additional cost of premature births in the United States is $2.9 billion/ year. This does not include all the costs of the taking care of the child after the baby leaves the hospital. The child may have permanent disabilities that include respiratory, gastrointestinal, immunological, brain, hearing and vision, motor, cognitive, behavioral, social-emotional issues. In other words, this refers to respiratory distress syndrome, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, death, cerebral palsy, developmental disorders, and cognitive impairment. Many of these impairments continue to adulthood. The total cost to the United States in 2005 is estimated to be $26.2 billion. In 2014, African-Americans had a 16.5% preterm birth rate. White pregnancies had a 10.3% preterm both rate. Hispanics had a 11.6% preterm birth rate.

Preterm delivery is not due to one factor but many factors. The recent research has highlighted cervical disease and progesterone deficiency. However, preterm labor may be caused by infection, vascular abnormalities, stress-nutrition, uterine over distention, abnormal allogenic recognition, allergy and also unknown factors.

I also have seen allergies and antibodies to progesterone. In my opinion, using an herb that is traditionally used by folk medicine practitioner to create miscarriage on the skin is NOT A GOOD IDEA. Herbs like mint and aloe are used traditionally to create miscarriage and are also used in cosmetics and toiletries. If progesterone is absorbed through the skin, then these abortion causing herbs can also be absorbed by the skin. More than likely some of these “miscarriage herbs” block progesterone at the receptor level. Progesterone is the natural hormone whose function is to maintain pregnancy.[7]

For instance, giving RU-486 (the morning after pill), a progesterone receptor blocker, at any time during pregnancy will induce a miscarriage through inducing cervical ripening. This means that progesterone action is essential to maintain the pregnancy. Animal studies also confirm that a blockade of the progesterone receptor will lead to preterm birth.[8]

There are some herbs known to cause miscarriage. Some of these herbs like mint and aloe are commonly found in cosmetics and toiletries. In my opinion, it would unwise to take these herbs during pregnancy. According to Vern Bullough mint (mentha) family that include sage, marjoram, thyme, rosemary and hyssop inhibit gonadatropic and prolactin secretion and were used to create miscarriage. They were mixed with sweet wine, juniper, cypress chips, and drunk. Rosemary is a common ingredient in some toiletries [9]. Buy any product from us, and you will get a list of herbs traditionally used to create miscarriage. In my opinion, these herbs that cause miscarriage should be avoided during pregnancy in either lotions and cosmetics and in food.

According to the ACOG and SMFM (American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine)recommendation for 2012 preterm birth progesterone is strongly recommended for singleton pregnancies for pregnancies with a previous preterm birth not even taking into account cervical length. The ACOG recommendation is to use 17-OHPC, a synthetic brand name progestin. They have recommended this since 2008. Secondly, they also recommend vaginal progesterone for singleton pregnancies with a short cervical length of 2 cm or less measure by transvaginal ultrasound found by mid pregnancy. The ACOG recommendation does not recommend progesterone use for singletons with an unknown cervical length or normal cervical length, for multiple gestations, twins or triplets, (never mind the cervical length), or premature rupture of membranes.[10-18]

You may watch the continuing medical education prevention of preterm delivery video here after signing up for a free medscape account. http://www.medscape.org/viewarticle/753509. 

Another Study Shows Progesterone Prevents Premature Births

Progesterone May Reduce Premature Births
Feb 6, 2003

By PAUL ELIAS, AP Biotechnology Writer

A North Carolina doctor presented results Thursday of a groundbreaking study that showed the hormone progesterone prevented premature births in a surprisingly high number of high-risk pregnancies.

"The evidence of this treatment's effectiveness was so dramatic, the research was stopped early," said the study's lead researcher, Dr. Paul Meis of Wake Forest University Baptist Medical Center.

Progesterone is naturally produced by the ovaries. It softens the uterus lining into a spongy bed that holds a fertilized egg.

Weekly injections of the hormone reduced the chance of premature births by 34 percent in the 306 high-risk women who received the therapy, the study reported. An additional 153 women were injected with a placebo. All the women had previously given birth prematurely, the single biggest indication of risk.

The study was carried out at the 19 centers that comprise the Maternal Fetal Medicine Units Network under the National Institutes of Health (news - web sites). Meis unveiled the results in San Francisco at the annual meeting of the Society for Maternal-Fetal Medicine.

"The results are so good that it's surprising," said Dr. Fredric Frigoletto, chief of obstetrics at Massachusetts General Hospital in Boston. "No intervention that we have ever applied has had any measurable effect. This is very good news."

Doctors have prescribed progesterone for years to help infertile and menopausal women.

Meis said progesterone had been previously toyed with as a preventive treatment for premature births in the 1960s and 1970s, but no one has completed a serious study on the subject.

"I think it's going to awaken people to an old idea that kind of slipped away," said Dr. Alan DeCherney, chair of the Obstetrics and Gynecology department at the University of California, Los Angeles.

Dr. Emile Papiernik, a French obstetrician, conducted a tiny progesterone study in 1970 that showed promise. But he said he couldn't interest any pharmaceutical companies or government agencies to fund a more comprehensive experiment.

"This has been sitting on the pharmacist's shelf for more than 30 years," Papiernik said.

In 2001, about 476,000 babies were born too soon in the United States — a 27 percent increase since 1981, according to the March of Dimes. One in eight babies was born before the 37th week of pregnancy, which is considered full term.

"The problem is huge," said Dr. Nancy S. Green, a New York City pediatrician and medical director of the March of Dimes. Last week she announced the organization's $75 million, five-year program to reduce premature births.

Babies born prematurely are at increased risk for neurological, hearing and behavioral problems. The average hospital charge in 2000 for a premature baby was $58,000, compared with $4,300 for a typical newborn, according to the March of Dimes.

Some of the increase in premature births can be attributed to more older women giving birth and the explosion of obesity in the country, Green said. But fully half of premature births have no known cause, Green said.

The March of Dimes said black women give birth prematurely at disproportionately high rates: 17.5 percent of all births to black women last year were premature, compared with the national average of 11.9 percent.

Frigoletto said that high rate has been studied extensively — but no definitive, scientific conclusions have been drawn.

In Meis' study, 59 percent of the women were black. The researchers concluded that race didn't influence the hormone's effectiveness.

"I think it really will attract a lot of interest," Meis said of the study. "This is the first fairly effective treatment for pre-term births."

Notes:

1. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, Thom E, McNellis D, Copper RL, Johnson F, Roberts JM. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med. 1996;334:567–572.

2. S. S. HASSAN, R. ROMERO, D. VIDYADHARI, S. FUSEY, J. K. BAXTER, M. KHANDELWAL, J. VIJAYARAGHAVAN, Y. TRIVEDI, P. SOMA-PILLAY, P. SAMBAREY, A. DAYAL, V. POTAPOV,J. O’BRIEN, V. ASTAKHOV, O. YUZKO, W. KINZLER, B. DATTEL, H. SEHDEV, L. MAZHEIKA, D. MANCHULENKO, M. T. GERVASI, L. SULLIVAN, A. CONDE-AGUDELO,1 J. A. PHILLIPS, and G. W. CREASY, Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2011 Jul; 38(1): 18–31.

3. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl JMed. 2007;357:462–469.

4. O’Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:687–696.

5. DeFranco EA1, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW 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 Obstet Gynecol. 2007 Oct;30(5):697-705.

6. Maria L. Brizot, MD, PhDcorrespondenceemail, Wagner Hernandez, MD, Adolfo W. Liao, MD, PhD, Roberto E. Bittar, MD, PhD, Rossana P.V. Francisco, MD, PhD, Vera L.J. Krebs, MD, PhD, Marcelo Zugaib, MD, PhD Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study. American Journal of Obstetrics and Gynecology, July 2015Volume 213, Issue 1, Pages 82.e1–82.e9.

7. Anderson S. Minjarez D, Yost NP, Word RA, J Clin Endocrinology Metab. 2008:93(6):2366-2374.

8. http://www.medscape.org/viewarticle/753509. Sign up for a free account to view the video. I highly recommend it.

9. Combs, CA. Vaginal progesterone for asymptomatic cervical shortening and the case for universal screening of cervical length. Am J Obstet Gynecol 2012;206:101-103.

10. Vern Bullough, Encyclopedia of Birth Control, 2001 ABC-CLIO, Inc. Santa Barbara, CA 126.

11. DeFranco EA, O’Brien JM, Adair, CD, et al. 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 Obstet Gynecol 2007;30:697–705. Fonseca EB, Celik E, Parra M, et al. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med 2007;357:462-469.

12. Fonseca EB, Bittar RE, Carvalho MH, et al. 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. Am J Obstet Gynecol 2003;188:419-424.

13. Hassan SS, Romero R, Berry SM, et al. Patients with an ultrasonographic cervical length ≤15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000;182:1458-1467. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multi-center, randomized, double-blind, placebo-controlled study. Ultrasound Obstet Gynecol 2011;38:18-31.

14. Iams JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med 1996;334:567-572.

15. Romero R. Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol 2007;30:675-686.

16. Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and meta-analysis of individual patient data. Am J Obstet Gynecol 2012;206:124.e1-19.

17. Romero R, Yeo L, Miranda J, et al. A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix. J Perinat Med 2013;41:27-44.

18. Sotiriadis A, Papatheodorou S, Makrydimas G. Perinatal outcome in women treated with progesterone for the prevention of preterm birth: a meta-analysis. Ultrasound Obstet Gynecol 2012;40:257-266.