A current hot topic in both fertility and pregnancy is progesterone--and for good reason! It is an essential and important part of pregnancy. In this conversation my colleague, Dr. Lucky Sekhon, an REI specialist, we discuss several of the important topics related to progesterone
Watch Here: The low down on progesterone in (in)fertility, early pregnancy loss, preterm birth, & short cervix!
In this video, we discuss:
Disorders related to impaired progesterone production or action may affect pregnancy success. A defect in corpus luteum function (ie, luteal phase defect) has been hypothesized to be a potential cause of impaired progesterone production and resultant infertility or pregnancy failure. However, it is controversial as to whether such a defect really exists and is related to miscarriage, and there is no consensus on the best method to diagnosis or treat luteal phase defect. As a result, luteal phase defect is not considered to be an independent cause of infertility.
You may have heard from someone in your social circle or online saying they received exogenous progesterone supplementation to prevent early pregnancy miscarriage and it was the miracle that saved the pregnancy. However, as Dr. Sekhon explains, a pregnancy in which there is low progesterone might be due to the fact that the embryo is not viable and the body is naturally ending the pregnancy. Human anatomy is complex and intricate- if an embryo has the wrong amount of chromosomes or some other irregularity, then the body will miscarry. Exogenous progesterone supplementation can potentially prolong a non-viable pregnancy.
A threatened miscarriage is vaginal bleeding in the presence of a closed uterine cervix and sonographic visualization of a viable intrauterine pregnancy. Low progesterone levels have been associated with an increased rate of miscarriage, but whether these low levels are the cause or consequence of a failing pregnancy is unclear.
ACOG says, “For threatened early pregnancy loss, the use of progestins is controversial, and conclusive evidence supporting their use is lacking.” The United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines affirm that the evidence is inconclusive but “data from meta-analysis of several small studies suggest that progestogens are better than placebo.” Note that a persistent limitation of these studies is the inability to control for the presence of better-established causes of pregnancy loss such as aneuploidy.
It can be defined as two or more consecutive failed clinical pregnancies as documented by ultrasonography or histopathologic examination (ACOG) or three consecutive pregnancy losses, which are not required to be intrauterine, including biochemical pregnancies for those undergoing in vitro fertilization. ASRM and the European Society of Human Reproduction and Embryology (ESHRE) define recurrent pregnancy loss (RPL) as the spontaneous loss of 2 or more pregnancies diagnosed by either serum or urine human chorionic gonadotropin.
It is not known if treatment with intramuscular progesterone or other progestins would improve the live birth rate in individuals with RPL. The ASRM 2012 guidelines on the evaluation and treatment of RPL state that “in patients with 3 or more consecutive miscarriages immediately preceding their current pregnancy, empiric progesterone administration may be of some potential benefit.” ACOG guidelines state that “women who have experienced at least 3 prior pregnancy losses may benefit from progesterone therapy in the first trimester.”
Both vaginal progesterone suppositories and intramuscular injections (17-OHPC) of progesterone have been used in those patients with a history of preterm birth in a prior pregnancy. A recent study looked at whether vaginal progesterone was better than 17-OHPC in the prevention of recurrent preterm birth. The results showed that vaginal progesterone did not reduce the risk of recurrent preterm birth when compared to 17-OHPC, but it may increase the time period to delivery. As a result, the authors recommend allowing patients with previous preterm birth vaginal suppositories or 17-OHPC. However, a more recent meta-analysis showed that vaginal progesterone did not reduce the risk of recurrent preterm birth for those with singleton gestations and a history of preterm birth. Finally, if a patient has a history of preterm birth, they may decide to have serial cervical length measurements rather than initiating progesterone supplementation earlier the pregnancy. In this scenario, progesterone supplementation should be started if the cervical length is <25mm.
As always, if you have have questions, talk to your obstetrical care provider!
I highly encourage you to watch this video if you are trying to conceive, have experienced RPL, or simply want to understand more about how the hormone progesterone plays a role in pregnancy. Beware of the information you find from influencers online who do not actually have a medical background! Getting your information from credible medical experts who work directly in the field is the best way to learn about this complex topic.
You can connect and learn more from Dr. Sekhon on her blog, The Lucky Egg. Be sure to subscribe to my YouTube channel and Podcast so you never miss a thing!
RCT Results: Vaginal Progesterone or 17-OHPC for Preventing Recurrent Preterm Birth?
Does Vaginal Progesterone Prevent Recurrent Preterm Birth When Cervical Length is >25 mm?
EPPPIC Meta-analysis Results: Progestogens for Preterm Birth Prevention
Meta-Analysis: Does Vaginal Progesterone Reduce the Risk of Recurrent Preterm Birth?
Evaluation and treatment of recurrent pregnancy loss: a committee opinion
Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234
Progestogens for preventing miscarriage: a network meta-analysis
Shannon M. Clark, MD, MMS is a double board certified ObGyn and Maternal-Fetal Medicine Specialist, and founder of Babies After 35. In her roles as a clinician, educator and researcher at UTMB-Galveston, she focuses on the care of people with maternal and/or fetal complications of pregnancy. Dr. Clark has taken a special interest in pregnancy after the age of 35, which according to age alone, is considered a high-risk pregnancy.
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