THE LUCKY EGG

Dr. Lucky Sekhon's Fertility Blog

Low progesterone causing miscarriage: A common misconception

What came first – the miscarriage or low progesterone levels? This is one of the most often asked questions when it comes to early pregnancy loss. Progesterone is THE major pregnancy hormone – it is literally PRO-gestation. That’s why it is an easy target and is so often blamed for when pregnancies aren’t successful and end in miscarriage. In most cases of pregnancy loss, low progesterone levels are a SYMPTOM rather than a CAUSE of abnormal pregnancy. In order to understand this, it is crucial to understand the role of progesterone in the menstrual cycle and establishment of early pregnancy.

At the start of each menstrual cycle, a limited cohort of the total number of eggs in the ovary are recruited to the surface of the ovary. Hormone signals from the pituitary gland in the brain (Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) are sent to the ovary and will randomly select a dominant follicle to grow, produce estrogen, and ovulate a single mature egg into the fallopian tube. The ruptured follicle that the egg was ovulated from then starts churning out progesterone – at this point that follicle is known as the Corpus Luteum. Hence, why the phase of the post-ovulation menstrual cycle is known as ‘luteal’.  If the egg does not result in pregnancy, the progesterone levels gradually decline and lead to breakdown of the uterine lining resulting in menstruation 12-14 days post ovulation. If the egg is fertilized and grows into an embryo that implants, the embryo will begin to produce the pregnancy hormone, beta-human chorionic gonadotropin (HCG). HCG acts as a signal that travels to the ovary and tells the Corpus Luteum to keep doing it’s thing – keep making that progesterone. Progesterone continues to stabilize and protect the lining of the uterus and helps to maintain the pregnancy. Eventually, at around 7-10 weeks of pregnancy, the placenta will be formed and will take over production of estrogen and progesterone to support the pregnancy over the 2nd and 3rd trimester. The Corpus Luteum regresses and dies off. 

Progesterone is essential for the maintenance of a healthy pregnancy. Up until the last decade, there was a long-held belief that some pregnancies resulted in miscarriage due to a dysfunction of the ovaries/corpus luteum – where there was not enough progesterone being made to support the pregnancy. This entity was called ‘Luteal Phase Defect’. Unhealthy pregnancies that end in loss are often observed to be associated with low progesterone levels. Based on this, women were (and still are) readily prescribed progesterone supplements in an effort to lower the risk of pregnancy loss in the first trimester. But we now know that low progesterone levels are MOST OFTEN a symptom of an unhealthy, dysfunctional pregnancy – due to lack of proper signaling (ie. low/insufficient HCG levels) to drive normal progesterone production from the ovary’s corpus luteum. Most miscarriages occur due to the embryo being genetically abnormal or uterine related factors such as fibroids or a septum in the uterine cavity that can interfere with proper implantation. Throwing progesterone at these problems will not make them go away. In fact, progesterone may actually stabilize the uterine lining and slow down the progress of a miscarriage and prolong the agony of waiting to pass the pregnancy and get on the road to recovery. 

Some women DO have dysfunctional menstrual cycles with a short luteal phase due to insufficient progesterone levels that lead to rapid progesterone decline to baseline levels and onset of the bleeding. This can occur due to underlying medical problems that impair normal hormone signaling from the pituitary gland – examples include starvation (eating disorders), excessive exercise, hypothyroidism, high prolactin levels, to name a few examples. Correcting these underlying causes of a dysregulated cycle is the key to treatment – not covering these problems up by supplementing progesterone. Anyone with a short luteal phase (<9-11 days between ovulation and onset of menstruation) should have a thorough evaluation for possible underlying causes. Sometimes self monitoring the timing of ovulation using ovulation predictor kits and other methods may be inaccurate – it could be helpful to have a monitored menstrual cycle using blood work and ultrasound to truly understand when ovulation is occurring and the actual length of the luteal phase. 

When it comes to progesterone, the most common question people ask their doctor is ‘what level should it be to ensure a healthy pregnancy?’

There is no clear answer to this question because there is NO single threshold. Just like the signals from the pituitary that cause ovulation (Luteinizing Hormone) are released in a pulsatile fashion – meaning the levels are not stable over time- progesterone is also produced in a pulsatile way. Therefore, a single random measurement may not provide the whole picture. In general, a progesterone level >3ng/ml a week after the LH surge/ovulation will confirm that ovulation occurred. Studies have shown that levels as low as 2.5ng/ml are associated with normal luteal phase gene expression activity in the lining of the uterus and that levels between 8-18ng/ml are associated with a normal appearance of luteal phase endometrial lining cells under a microscope. If I see progesterone levels greater than 10ng/ml, I find that encouraging – but I would never make a judgment about the viability of an early pregnancy based on a single progesterone level. 

Progesterone Supplementation:

When it comes to IVF pregnancies, the follicles which have been drained of fluid to collect the eggs will not function like normal corpus luteums and progesterone supplementation is required to support early pregnancies from a fresh transfer, approximately a week after retrieval. If a frozen embryo transfer, progesterone is absolutely necessary since no recent ovulation has occurred. The estrogen and progesterone leading up to a frozen transfer are designed to mimic the natural menstrual cycle – with the luteal phase being produced by progesterone supplementation. This can be in the form of intramuscular injections or a combination of oral and vaginal progesterone. In pregnancy conceived without IVF, supplementation is not considered harmful but are unlikely to reverse or modify the risk of miscarriage – as a faulty corpus luteum and low progesterone levels are not the driving cause behind miscarriage. I would caution anyone from just adding in progesterone after ovulation, in untreated cycles, as this could potentially detract from your chance of success. If progesterone is started too early, it could open up the window of implantation in the lining of the uterus too early and make the lining less receptive to an implanting embryo. There is some weak evidence of a potential benefit of progesterone supplementation in women with recurrent miscarriages with vaginal bleeding. The decision of progesterone supplementation should be individualized based on the particular case. 

The bottom line is – if you had a miscarriage and have no known underlying hormonal imbalances or pituitary/thyroid problems, it was VERY unlikely caused by a progesterone deficiency or resistance of your body to the effects of progesterone. If such problems exist, they would be extremely rare. When it comes to low progesterone – it is the consequence of an unhealthy pregnancy, not the cause. As much as we wish to have control and the ability to use progesterone like a band-aid of sorts, to salvage and rectify any early pregnancy abnormalities, we know that it seldom is the answer. The important takeaway is that you should not regret not taking progesterone – and there was likely nothing that could have been done to modify the outcome. Miscarriage is NOT your fault and NOT in your control. The only thing we can do is observe and collect data points as early indicators of whether a pregnancy will be likely to persist – and progesterone and HCG levels are the most useful predictors of pregnancy health and success.

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