Progesterone, known in the scientific community as P4, plays a crucial role in fertility. Understanding how it affects fertility and pregnancy, how it’s created, its normal levels, and when during a woman’s cycle is the best time to test its level, should be common knowledge to anyone who has been trying to conceive for more than 9 months.
Introduction
Derived from cholesterol, progesterone is a steroid hormone that is produced mainly by the ovaries and plays a significant role in the reproductive system. After ovulation, the main task of progesterone is to create a healthy endometrial environment that will eventually allow for a successful implantation. During the first 12 weeks of pregnancy, progesterone continues to stimulate the blood vessels of the endometrium providing nutrients to the developing embryo. The placenta is fully developed around week 12 and at that time it becomes the primary producer of progesterone.
Background
During the follicular phase the level of progesterone remains very low – typically under 1ng/mL. Once a follicle releases a mature egg (ovulation), what’s left of the follicle becomes known as the corpus luteum. This becomes a temporary endocrine gland that starts to secrete progesterone and it continues to do so until there’s no pregnancy. However, if the egg was fertilized and the now embryo was successfully implanted in the endometrium, the embryo begins to secrete the hormone hCG (human Chorionic Gonadotropin) which signals the corpus luteum to continue secreting progesterone. After 12 weeks of gestation the placenta takes over the pregnancy and, among many other jobs, produces progesterone. The corpus luteum is no longer needed and it degenerates.
The Importance of Progesterone
The main function of progesterone is to prepare the endometrium so that an embryo can implant and grow. Decidualization, a process that occurs in the endometrium during the menstrual cycle and pregnancy, prepares the body for implantation and pregnancy. This process is driven by progesterone and involves the functional and morphological changes that occur within the endometrium to form the thickened lining - the decidual lining.
A healthy decidual lining is key for proper implantation since it is this lining that provides nutrients to the embryo, shelters the developing embryo from the maternal immune response, and regulates invasion of the trophoblast (the outer layer of the blastocyst penetrates the decidual to have access to blood supply). If there is no implantation, the decidual lining is shed gradually over several days during the period.
How Much Progesterone
As mentioned earlier, once ovulation occurs the corpus luteum begins to secrete progesterone and it will stop if there is no pregnancy. Around cycle day 21, or 7 days after ovulation, the levels of progesterone should be at its highest if there is no pregnancy. While some experts believe that a serum level of at least 5 ng/mL will confirm ovulation, studies show that for proper implantation to take place the normal range for progesterone around CD-21 is between 10 to 20 ng/mL. A paper published by Cell, a monthly peer-reviewed open-access scientific journal that covers all aspects of cell and molecular biology, mentioned that, referring to the corpus luteum:
“ This gland secretes significant amounts of P4 - more than 10 ng/mL, initiating a cascade of events crucial for the prospect of a future pregnancy”
On another publication, a meta-analysis review published in 2021 by Fertility and Sterility, looked at a number of studies where different levels of progesterone were analyzed. The review grouped the different studies according to the serum progesterone thresholds they reported (<10, 10–20, >20–30, and >30 ng/mL). The review concluded that: “This systematic review suggests that there is a minimum clinically important serum luteal progesterone level of approximately 10 ng/mL associated with optimal rates of ongoing pregnancy (OPR) or live birth (LBR)”. The review also mentioned that the group with progesterone levels between 10 and 20 ng/mL had an increased OPR or LBR. However, there was no correlation with serum progesterone level measurements between 20 and 30ng/mL and OPR or LBR. This meta-analysis included only one study where the serum level of progesterone was higher than 30ng/mL. Due to the small pool of this particular study, a meta-analysis of adjusted effect estimates was not possible for OPR or LBR.
“ This systematic review suggests that there is a minimum clinically important serum luteal progesterone level of approximately 10 ng/mL associated with optimal rates of ongoing pregnancy (OPR) or live birth (LBR)”
More recent studies are showing that progesterone is secreted in a pulsatile pattern where
concentrations during the mid-luteal phase can exhibit large and rapid fluctuations. Because of these findings, a progesterone blood test drawn approximately one week after ovulation is only an estimate of the amount of serum progesterone. Some researchers are recommending three blood samples during the luteal phase, with a total serum progesterone value of 15 ng/mL or more to indicate normal luteal function.
In contrast, organizations like Mayo Clinic continue to say that: “Typically, day 21 to 23 serum progesterone concentrations of more than 10 ng/mL indicate normal ovulation and concentrations below 10 ng/mL suggest anovulation, inadequate luteal phase progesterone production, or inappropriate timing of specimen collection.
“ ...progesterone concentrations of more than 10 ng/mL indicate normal ovulation and concentrations below 10 ng/mL suggest anovulation...”
Progesterone and Acupuncture
While there are not many human studies showing the effect of acupuncture on progesterone, there is a substantial amount of animal studies. One of these studies, published in 2023 by Frontiers in Endocrinology concluded that: “Acupuncture may restore the estrogen and progesterone balance in COH rats and the forward shift of the implantation window to a certain extent, improving the endometrial receptivity and finally improving the pregnancy rate of COH rats”. Another study published in 2015 by the Chinese Journal of Integrative Medicine concluded that: “Acupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats”.
Conclusion
Low levels of progesterone (less than 10ng/mL) can negatively affect the endometrium, decreasing the chances of implantation. Understanding when and how progesterone is created in the body and what its levels should be during implantation are crucial for a successful pregnancy. In several studies (animal) acupuncture has been shown to have a positive effect in restoring the natural balance of progesterone.
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