The role of progesterone in the prevention of early pregnancy loss (miscarriage)

This issue, which has been debated for decades, is revisited in the December 6, 2021 issue of Contemporary OB/GYN. Since it is a current and important issue, it has been opened to discussion once again.

Known:

Pregnancy loss, namely miscarriage, occurs in 30 percent of total pregnancies (including very early pregnancies that have not been clinically diagnosed yet) and in 10-15 percent of pregnancies that can be clinically diagnosed.

Low blood progesterone levels in early pregnancy increases the likelihood of a pregnancy ending in miscarriage.

Progesterone is essential for the continuation of pregnancy, especially in the early stages. After the ninth gestational week, its role in the continuation of pregnancy decreases or even ends, since its synthesis is started by the placenta.

In the first half of the menstrual cycle of women with regular menstruation, only estrogen is secreted from the ovaries, while in the second half, in addition to estrogen secretion, progesterone is secreted after ovulation. In the absence of ovulation, that is, if progesterone is not secreted, menstruation is irregular and delayed. In order for menstrual cycles to be regular, there must be ovulation.

In case of pregnancy, progesterone develops the lining (endometrium) in the uterus, making it suitable for the embryo to settle.

In the absence of pregnancy, the production of progesterone (and estrogen) from the ovaries ceases and menstrual bleeding begins.

If we divide the pregnancy into three quarters, in the second and third trimesters (between 12-40 weeks), progesterone inhibits the contraction of the uterus, suppresses the mother’s immune system to prevent the body’s rejection against the baby, which plays the role of a foreign antigen, thus ensuring the continuation of the pregnancy.

The question that scientists have been working on for decades is: Does exogenous administration of progesterone, which plays such an important role, prevent possible miscarriages and premature births?

Threat of miscarriage

If vaginal bleeding occurs when the cervix is ​​closed and a live pregnancy is seen on ultrasound, this situation is called a threat or danger of miscarriage. In case of low progesterone levels in the blood, early pregnancy losses, that is, miscarriages, are more common. Is the cause of low progesterone here an unhealthy pregnancy or does low progesterone cause pregnancy loss? This issue is open to discussion.

The results of 7 scientifically accepted studies on 696 pregnant women showed that exogenous progesterone administration reduced the risk of miscarriage by 36 percent. In a larger study published later, external administration of progesterone did not reduce the risk of miscarriage in 4153 pregnant women with bleeding who were diagnosed with threatened abortion. It has been confirmed once again in the same studies that progesterone does not reduce the risk of miscarriage in pregnant women who have had 3 consecutive miscarriages. In the evaluation of 4833 pregnant women, which was done by combining the data of both studies, administration of progesterone reduced the risk of miscarriage by 30 percent. It should be noted that the reliability of the studies is not very high and there is no difference between the pregnant women using and not using progesterone when the live birth rates are compared.

In summary, the agreed conclusion is that although no medication is given, external administration of progesterone slightly reduces the risk of miscarriage, but the quality and reliability of these studies are not very high.

recurrent pregnancy loss

It is defined as having 2 or more miscarriages in a row. An average of 60 percent of early miscarriages are chromosomal disorders, that is, genetically abnormal pregnancies. The earlier the miscarriage week, the higher the probability of miscarriage due to abnormal pregnancy, the later the lower the probability. Other causes of miscarriage include anatomical and structural disorders in the reproductive organs, immune system abnormalities (antiphospholipid syndrome) and hormonal imbalances. Despite all technological advances, only half of early pregnancy losses can have a definitive cause of miscarriage. Progesterone hormone is essential for the baby to settle in the uterus and for the healthy continuation of the pregnancy. Despite research, the cause of low progesterone may not be found or it may be associated with problems in thyroid hormones and high prolactin.

Scientific studies have shown that external progesterone application until the 12th week does not increase live birth rates, that is, it is not beneficial. On the other hand, a worldwide practiced habit among physicians to memorize is the external administration of progesterone to pregnant women with a history of miscarriage. Another reason for this approach is the desire and demand of women who have had abortions to do something, in other words, the expectation of a treatment from the physicians. Considering that the probability of giving birth to a healthy baby after miscarriage is over 50 percent even if no treatment is applied, it is not difficult to predict that if the pregnancy ends with a healthy birth, the success will be attributed to the progesterone given, and if the pregnancy results in miscarriage again, it will be thought that the miscarriage cannot be prevented despite all the treatments.

How safe is progesterone administration during pregnancy?

In a study, it was reported that the frequency of hypospadias increased 3.7 times in male babies of pregnant women using progesterone. The type of progesterone administered in this study was not specified. Even if it is to be given to pregnant women, progesterone should be natural (micronized progesterone or dydrogesterone), not synthetic. In another study, it was reported that the frequency of congenital heart defects increased 2.7 times in babies born with dydrogesterone. There was no increase in the frequency of congenital anomalies with micronized progesterone.

As a result The benefit of progesterone therapy in early pregnancy has not been proven. What is certain is that there is absolutely no benefit to administering progesterone in cases of early pregnancy at risk of miscarriage if there is no previous history of recurrent miscarriage. In addition to previous abortions, in the presence of a viable pregnancy and vaginal bleeding during the current pregnancy, progesterone administration may be considered for abortion prevention, although there is no evidence. The patient should be discussed in detail and scientific data should be shared.

Although it is a common practice, it is not yet clear exactly when progesterone is needed, the appropriate dose and mode of administration, the duration of the treatment, and the cost-effectiveness.

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