Progesterone Treatment during pregnancy to avoid Miscarriage

Progesterone is critical to maintaining a pregnancy but when is it okay to stop progesterone in IVF and frozen embryo transfer cycles? Find out on today’s episode of InfertilityTV.
In order for an embryo to implant in the uterus, the uterine lining must first be prepared with estrogen followed by progesterone. In order to prevent a miscarriage, progesterone must continue to be present after the embryo implants. In a natural pregnancy, progesterone is initially produced by the ovaries. Eventually, the placenta will take over production of progesterone from the ovaries..
In an IVF cycle, some of the medications used to prevent early ovulation. Like Lupron or Ganirelix can compromise the progesterone production from the ovaries. Also, doing an egg retrieval can further reduce progesterone production. In a frozen embryo transfer, all of the hormones used to prepare the uterus are given to a woman so there is no progesterone production from the ovaries at all. So in both cases, extra progesterone must be taken by a woman until the progesterone production from the placenta is adequate to support the pregnancy..
But when does this shift of progesterone production from the ovaries to the placenta occur? Scientists were able to figure this out by doing studies in monkeys. They found that if you remove the ovaries of a pregnant monkey before the 7th week of pregnancy, progesterone levels dropped and then the pregnancy always miscarried. On the other hand, if the ovaries were removed after the 8th week, progesterone levels stayed about the same and miscarriages didn’t occur. However, if you removed the ovaries before the 7th week but you gave the monkey progesterone then the progesterone levels didnt drop and the pregnancies continued just fine..
The same timing occurs in humans. Its always possible for there to be a little variation from one woman to the next so at top IVF programs like ours at the Naperville Fertility Center, we keep progesterone going until about 9 to 10 weeks..
Here is how to determine how many weeks your pregnancy is. If you are doing a blastocyst transfer, then you are 2 weeks and 6 days along on the day of transfer so you should continue progesterone for another 6-7 weeks..
I didn’t talk about the different types of progesterone in this video. You need to learn about the specific types of progesterone and how to use them to maximize your chances for IVF success. Check out this video about Crinone vaginal progesterone next..
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You mentioned that because of your past pregnancy history, you’re interested in taking progesterone during this pregnancy, and wondering if it will increase the chances of you doing well, and want to know what kind you should take. I suggest talking with your doctor about it, because progesterone is given to some women who have a history of preterm delivery because studies have shown that it can decrease their chances of delivering preterm by helping to sustain the pregnancy and keep a woman pregnant longer. But your doctor will decide if it’s appropriate for you, and if so, prescribe the right kind and dosage. I sincerely hope the best for you during this pregnancy, and if you have any other questions for me in the future, feel free to ask them on our Facebook page at http://www.facebook.com/IntermountainMoms, and recommend us to your friends and family too

The Fetal Medicine Foundation webinar, organised by the legend Professor Kypros Nicolaides, was attended by over 7000 delegates from 154 countries. In this lecture, you can hear Professor Arri Coomarasamy discuss the role of progesterone hormone for the prevention miscarriages. What is evidence for effectiveness and safety? What does the totality of evidence, summarised in a meta-analysis show? Which progesterone, what dose, what regimen? This video has the answers! It also covers the two landmark trials on the subject, the PROMISE and PRISM trials, both of which were published in the New England Journal of Medicine.

Dr. Alberto Sirven, Medical Director of the West Kendall OB/GYN Program and Women and Infant Credentials Committee Chairman with West Kendall Baptist Hospital, says if you have had recurrent miscarriages, which is more than three miscarriages, you should have a complete workup. He explains sometimes patients need to take aspirin or progesterone, even though it may not save the pregnancy..
He points out progesterone does not affect pregnancy and could help patients with recurrent miscarriages..
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The PRISM trial is the largest ever randomised trial in miscarriage prevention; it recruited more than 4000 women from 48 hospitals in the UK. It evaluated the effects of progesterone hormone in women with early pregnancy bleeding. Overall, there was a 3% increase in live birth rate with progesterone, compared with placebo, but the finding was associated with some statistical uncertainty (RR 1.03, 95% CI 1.00 to 1.07, p = 0.08). However, a clear benefit was found for women with the dual risk factors of early pregnancy bleeding and a history of (any number of) previous miscarriages (RR = 1.09, 95% CI 1.03 to 1.15, p = 0.003). The larger the number of previous miscarriages, the greater the live birth rate, with progesterone treatment. For women who had 1 or 2 previous miscarriages, and have current pregnancy bleeding, progesterone was associated with a 4% increase in live birth. For women with 3 or more previous miscarriages, and have current pregnancy bleeding, progesterone was associated with a 15% increase in live birth. There were no evidence of any safety concern from progesterone use. Our clinical recommendation is that for women with early pregnancy bleeding and a history of any number of previous miscarriages, progesterone treatment should be considered. Our recommended regimen is vaginal Utrogestan 400mg twice daily from the time of presentation with bleeding to 16 weeks of gestation..
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This trial was funded by the NIHR-HTA programme, and supported by the Tommy’s National Centre for Miscarriage Research. The trial was led from the Institute of Metabolism and Systems Research at the University of Birmingham, facilitated by the Birmingham Clinical Trials Unit..
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Key publications are:
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A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Kriedt K, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingam N, Watkins L, Wykes C, Horne A, Jurkovic D. N Engl J Med. 2019 May 9;380(19):1815-1824. doi: 10.1056/NEJMoa1813730. PMID: 31067371.
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Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. Coomarasamy A, Devall AJ, Brosens JJ, Quenby S, Stephenson MD, Sierra S, Christiansen OB, Small R, Brewin J, Roberts TE, Dhillon-Smith R, Harb H, Noordali H, Papadopoulou A, Eapen A, Prior M, Di Renzo GC, Hinshaw K, Mol BW, Lumsden MA, Khalaf Y, Shennan A, Goddijn M, van Wely M, Al-Memar M, Bennett P, Bourne T, Rai R, Regan L, Gallos ID. Am J Obstet Gynecol. 2020 Jan 29. pii: S0002-9378(19)32762-0. doi: 10.1016/j.ajog.2019.12.006. PMID: 32008730.
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The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM Trial. Okeke Ogwulu CB, Goranitis I, Devall AJ, Cheed V, Gallos ID, Middleton LJ, Harb HM, Williams HM, Eapen A, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Deb S, Duncan WC, Ewer AK, Hinshaw K, Holland T, Izzat F, Johns J, Lumsden M, Manda P, Norman JE, Nunes N, Overton CE, Kriedt K, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingham N, Watkins L, Wykes C, Horne AW, Jurkovic D, Coomarasamy A, Roberts TE. BJOG. 2020 Jan 30. doi: 10.1111/1471-0528.16068. PMID: 32003141