Case #1: A 38-year-old woman has just experienced her third miscarriage at about six weeks pregnant. Her physician told her that her blood progesterone level was low and that this low level might be the reason for her miscarriage. The physician also recommended that she begin progesterone with her next pregnancy to prevent miscarriage.
Case #2: A 33-year-old woman, who has never been pregnant, has been attempting pregnancy for the past 2 years without success. Her menstrual periods occur every 28 to 30 days and the evaluation of her male partner demonstrates a normal semen analysis. Her physician ordered laboratory testing, including serum progesterone, on menstrual cycle day 21. She was advised that all of her testing was normal except for a low progesterone value of 8 and that taking progesterone in the second half of her cycle may help her become pregnant.
The above cases illustrate some very common scenarios for patients and couples struggling with repeated miscarriages as well as infertility. The common link binding the two is the hormone progesterone. In order to determine if the use of progesterone will be helpful in either of these cases, it is important that people understand where progesterone comes from.
Progesterone and estrogen are some of the natural hormones that result from the complex interactions between the hormones produced by the brain, the ovary and specifically the cells making up the ovary. Among the most important cells within the ovary are the eggs.
When the brain and eggs are healthy, their interactions are smooth. Healthy eggs are released into the fallopian tube, and will be potentially fertilized by sperm, leading to an embryo (and pregnancy). Healthy eggs will continue to produce normal amounts of progesterone and estrogen and, if fertilized by healthy sperm, will have a greater likelihood of developing into a healthy child.
The progesterone that is produced by healthy eggs, and ultimately the resulting embryo, respond to the signals from the brain in a pulsatile, or up and down, manner. In other words, the levels of progesterone produced by healthy eggs are not static but fluctuate with time. Therefore, the ability to accurately determine the health of human eggs or embryos by single, or even multiple, progesterone levels is very difficult. Furthermore the actual level of “normal” progesterone has only been agreed upon to determine ovulation and this value is any level greater than or equal to 2. Attempts to establish levels of progesterone that will guarantee a normal pregnancy have not been successful.
Ultimately, if the human egg is flawed or compromised there is a far greater likelihood that the resulting embryo will be flawed and if progesterone levels are obtained it is more likely that the levels will be “low”. When a health care provider sees the “low” progesterone value the tendency is to advise the patient to begin taking a progesterone supplement, either orally or vaginally. In cases with a flawed or unhealthy embryo, the use of progesterone does nothing to improve the embryo and may result in sustaining a pregnancy that would otherwise have miscarried earlier.
There are many examples were women have experienced miscarriages and were prescribed progesterone supplementation in the next pregnancy and went on to successfully deliver. These cases are more about the coincidental and eventual fertilization of a healthy egg with healthy sperm and the resulting healthy embryo than the success of progesterone supplementation. There are just as many examples of women with repeated miscarriages who have been given progesterone supplementation who still continue to have miscarriages.
The likelihood of women having unhealthy or damaged eggs with the resulting unhealthy embryos increases with the following:
- Number of years of infertility
- The woman’s age
- Her personal history of smoking or exposure to second hand smoke
- Prior treatment with pelvic or abdominal radiation therapy or chemotherapy
Women with these risks factors are more likely to experience fertility problems including repeated miscarriage. Additionally, there can be a multitude of other problems that may be causing problems including abnormal female anatomy and abnormalities with the male partner’s semen parameters.
Researchers have attempted to demonstrate consistent significant improvements in delivery rates with the use of supplemental progesterone for women with repeated miscarriages without success. Progesterone is still prescribed to treat repeated miscarriages since there is no evidence that its use will harm the mother or baby in the first trimester, but its actual value as a therapy is overestimated. The use of progesterone as a therapy for unexplained infertility or to treat the “low” progesterone level as noted in case # 2 is even more problematic for the reasons described above.
Currently the only cases where progesterone use is still considered standard of care relate to the assisted reproductive technologies of in vitro fertilization (IVF), egg and embryo donation. All of these procedures can typically involve significant alterations in the hormonal environment which may disrupt the normal hormonal mechanisms that are in play for natural conception.
Patients should understand that role of measuring progesterone levels in cases of repeated miscarriages or as part of the evaluation of the infertile woman is very limited as is the role for progesterone therapy in cases not involving assisted reproductive technology. For women and couples struggling with these issues there are more valuable testing and treatment regimens that are available through consultation with a qualified specialist in the treatment of infertility.
Estil Y. Strawn, Jr. M.D. is doubly board certified in Reproductive Endocrinology and Infertility and Obstetrics and Gynecology. He is the medical director of the Froedtert and Medical College of Wisconsin Reproductive Medicine Center. Dr. Strawn is also full professor with tenure at the Medical College of Wisconsin where he serves as the director of the division of Reproductive Endocrinology and Infertility in the department of Obstetrics and Gynecology. Dr. Strawn blogs monthly with Attain Fertility. Dr. Strawn has been helping patients overcome their fertility problems for 19 years, and has directed a center that is one of the largest providers of fertility services in the state of Wisconsin. This center provides some of the most advanced types of technologies in the country including pre implantation genetic diagnosis (PGD), egg freezing, egg and embryo donation, gestational carriers, as well as robotic surgery for uterine fibroids and reversal of fallopian tube sterilization.