Doing Something vs. Doing Nothing: Luteal Phase Deficiency and Progesterone Supplementation
Friday, August 3, 2012
Joshua U. Klein, MD in Female infertility, IVF, Research, unexplained infertility

Most women who have undergone an infertility workup, and almost all women who have gone through infertility treatment, have probably been tested for their progesterone level at some point in the process. A recent statement published by the American Society for Reproductive Medicine (ASRM) provides a good opportunity to revisit what we know (and what we don’t) about the role of progesterone in infertility treatment.

Broadly speaking, progesterone is the hormone that supports pregnancy. Discovered in the 1930’s at the University of Rochester, pro-gest-er-one was named for its role as the “pro-gestational (i.e. supporting gestation, or pregnancy) steroidal ketone.” During a natural menstrual cycle, as part of the highly synchronized natural interplay between the ovaries and the uterus that occurs each month in order to facilitate the possibility of pregnancy, progesterone is produced starting just after ovulation; the source of the progesterone, conveniently enough, is actually the very follicle left behind by the egg that has been ovulated. This structure, called the “corpus luteum,” can usually be seen on transvaginal ultrasound within a couple of days after ovulation. The main job of the progesterone at this point is to transform the cells in the uterine lining (aka endometrium) into a surface that will be receptive to the implantation of a fertilized egg (aka embryo).

The corpus luteum typically continues to produce progesterone for about 12-14 days; at that point, if no embryo has implanted, the corpus luteum disintegrates, and the resulting drop in progesterone causes a menstrual bleed.  If, however, the egg that was ovulated is fertilized and the resulting embryo implants in the lining of the uterus, the embryo itself produces the hormone hCG (human chorionic gonadotropin) and “rescues” the corpus luteum, allowing it to continue producing progesterone. Progesterone, in turn, supports the continued growth of the pregnancy. Quite poetically therefore, it turns out that the pregnancy needs progesterone as much as the source of the progesterone (the corpus luteum) needs the pregnancy (for hCG). If the progesterone production is somehow interrupted -- for example, if the ovary containing the corpus luteum is surgically disturbed or removed during this period of time (up to about 8 weeks gestation, at which the point the placenta takes over progesterone production), the pregnancy will most likely fail, resulting in miscarriage. 

Given the critical role that progesterone plays in “supporting” pregnancy, it has long been speculated that progesterone deficiency, referred to as “luteal phase deficiency (LPD),” might be an important cause of infertility in couples who have no other obvious issue. As the recent ASRM statement confirms, however, whether or not LPD is a real cause of infertility in otherwise healthy women is doubtful at best. Furthermore, even if we assume LPD is real, there is little convincing evidence that treating LPD (typically with supplemental progesterone) will improve the situation. An important exception to this statement is in IVF/ART cycles (as opposed to non-medicated cycles or IUI cycles), when luteal function is clearly interrupted, and supplementing progesterone has been shown to be important. (Tangentially, new data actually questions whether we need to continue the progesterone supplementation as long as we do)

ASRM summarizes our current knowledge about LPD as follows:

  1. Abnormal luteal function may occur as the result of a medical condition (e.g., elevated prolactin, abnormal thyroid function), and infertile women should be investigated for these disorders with appropriate treatment of identified conditions.
  2. No diagnostic test for luteal phase insufficiency has been proven reliable in a clinical setting. The roles of basal body temperature, luteal progesterone levels, endometrial biopsy, and other diagnostic studies have not been established, and performance of these tests cannot be recommended.
  3. No treatment for luteal phase insufficiency has been shown to improve pregnancy outcomes in natural, unstimulated cycles.
  4. Luteal support after ART procedures with progesterone or hCG improves pregnancy outcomes, but hCG increases the risk of OHSS.
  5. There is no proven role in adding progesterone or hCG for luteal support once a pregnancy has been established. Use of supplemental progesterone, in a non-ART cycle beyond the time of expected menses (i.e., 2 weeks after ovulation), is not proven beneficial.


1. The Clinical Relevance of Luteal Phase Deficiency. Practice Committee of ASRM. Fertility and Sterility 2012.

2. Early progesterone cessation after in vitro fertilization/intracytoplasmic sperm injection: a randomized, controlled trial. Kohls et al. Fertility and Sterility 2012.

Article originally appeared on Fertility Reviews (
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