Low progesterone is associated with, but does not cause, infertility. There is no effect on fertilization of your eggs or the implantation of an early embryo in your uterus. However, low progesterone can interfere with further development of your embryo and fetus after implantation. This can lead to a nonviable pregnancy or miscarriage during your first trimester.
Effect of Low Progesterone on Implantation
Progesterone is essential to mature the uterine lining (endometrium) for implantation of the early embryo. Therefore, many specialists assumed low levels after ovulation (luteal phase deficiency) might cause failure of implantation and reduce your fertility at this stage. However, current evidence does not show low progesterone during the luteal phase interferes with implantation.
Evidence From a Study
A study of 20 women published in the Journal of Clinical Endocrinology and Metabolism in 1991 measured the urinary levels of metabolites of estrogen and progesterone during the peak of the luteal phase of the menstrual cycle. The authors reported the levels of hormones were similar whether a woman had an early pregnancy loss or a successful pregnancy. They concluded that the early losses were not related to a deficiency in progesterone or other ovarian hormones in the luteal phase.
Professional Fertility Society Opinion
There is no difference in pregnancy rates based on the level of progesterone at the midluteal phase. According to a 2015 American Society of Reproductive Medicine (ASRM) Practice Committee Opinion on luteal phase deficiency, in the absence of other abnormalities of the menstrual cycle, low progesterone in the luteal phase does not appear to affect fertility or reduce normal pregnancy rates. Instead, most failures of implantation, chemical pregnancies, nonviable fetuses, and other early losses are because of chromosomal abnormalities, ASRM concludes.
Effect of Low Progesterone on Early Pregnancy
After implantation, low progesterone during early pregnancy can affect your fertility - defined as the inability to carry a pregnancy to viability. Without enough progesterone from the corpus luteum in your ovary, the placenta and fetus cannot continue to develop, which leads to a nonviable fetus, early fetal loss, and miscarriage.
Progesterone Level in Viable and Nonviable Pregnancies
Progesterone output from the corpus luteum increases with pregnancy. A study reported in 2012 in the British Medical Journal found measuring a single progesterone level in early pregnancy can distinguish between a viable versus a nonviable pregnancy. A high progesterone level early in pregnancy is considered a sign of a normal, viable pregnancy. The level will be lower than expected if you have an abnormal pregnancy, such as an ectopic implantation or other nonviable early fetus.
Tests of Progesterone in the Luteal Phase
Doctors often use two tests to evaluate your progesterone status and examine its effect on the endometrium. However, neither test is reliable to diagnose progesterone or endometrial deficiency in the luteal phase:
- Progesterone level: Progesterone increases on the day of ovulation and peaks seven days later (midluteal phase). A normal blood level around that day was used as standard evidence of normal ovulation and corpus luteum function. However, a 2016 paper published at NCBI notes the test is not reliable for diagnosis of low progesterone because the hormone secretes in pulses. Blood levels can range widely, depending on when it is performed in relation to the timing of the pulses.
- Endometrial biopsy: A biopsy of the uterine lining just before a period shows the extent of progesterone on the endometrium in preparation for implantation. However, according to Fertility and Sterility, the endometrial biopsy is not a good indicator of low progesterone or pregnancy rates.
Treatment of Progesterone Deficiency
Although there is no reliable test of presumed progesterone deficiency in the luteal phase or evidence that treatment can improve viable pregnancy rates, some doctors may prescribe treatment, especially in cases of unexplained infertility. The 2008 Fertility and Sterility article reviews two forms of treatment:
- Human Chorionic Gonadotropin (HCG): Given as an injection, HCG boosts/prolongs the function of the corpus luteum to produce normal amounts of progesterone until pregnancy is established (positive pregnancy test).
- Progesterone support: This therapy is used after ovulation to supplement the progesterone produced by the corpus luteum. It is most often used as vaginal suppositories or intramuscular injections but can be taken by mouth.
Because of the lack of evidence for improved pregnancy outcomes, the ASRM Practice Committee Opinion does not advise luteal phase hormone therapy with HCG or progesterone unless you are undergoing an assisted reproductive technology (ART) procedure, such as in vitro fertilization (IVF). Pituitary suppression drugs used during ART cycles can interfere with corpus luteum function and progesterone production. In this situation, treatment increases pregnancy rates and reduces miscarriages.
Other Drugs for Abnormal Menstrual Cycles
If you are not making enough progesterone because your menstrual cycles are abnormal, and you are not ovulating monthly, your doctor might prescribe other drugs such as clomiphene citrate (Clomid). These drugs improve ovulation and luteal phase progesterone by organizing the hormonal events of the follicular phase.
Clomid is most often prescribed to induce regular ovulation in women who skip or have no periods, as reviewed by Yen and Jaffe's Reproductive Endocrinology, (chapter 5, page 703). You might also receive Clomid if you have slightly shorter or longer cycles or bleeding between periods when the rest of your infertility evaluation is normal.
Causes of Low Progesterone
Progesterone increases after ovulation and falls just before your next period when the corpus luteum dies. The level of the hormone during the luteal phase depends on normal cycling of the reproductive hormones during the first half of the cycle (the follicular phase) and on normal ovulation. The following problems can cause low progesterone production:
- Abnormal secretion of hormones of the hypothalamus and pituitary glands
- Inadequate growth of the ovarian follicles and eggs during the follicular phase
- Failure to ovulate an egg so no progesterone is made
- Early ovulation of an immature egg such that the remaining corpus luteum can't make enough progesterone
- Early death of the corpus luteum after ovulation so little or no progesterone is made
- Use of pituitary suppression drugs during ART procedures
- Aging of ovarian follicles and eggs (perimenopause or premature ovarian failure)
- Hormonal disorders, such as polycystic ovarian syndrome (PCOS) and thyroid and adrenal disorders, which interfere with ovulation and cause irregular periods
- Endometriosis of the ovaries, which can affect ovarian function and ovulation