The inadequate corpus luteum

Abstract

The corpus luteum is the source of progesterone in the luteal phase of the cycle and the initial two-thirds of the first trimester of pregnancy. Normal luteal function is required for fertility and the maintenance of pregnancy. Progesterone administration is increasingly used during fertility treatments and in early pregnancy to mitigate potentially inadequate corpus luteum function. This commentary considers the concept of the inadequate corpus luteum and the role and effects of exogenous progesterone. Progesterone supplementation does have important beneficial effects but we should be wary of therapeutic administration beyond or outside the evidence base.

Lay summary: After an egg is released a structure is formed on the ovary called a corpus luteum (CL). This produces a huge amount of a hormone called progesterone. Progesterone makes the womb ready for pregnancy but if a pregnancy does not happen the CL disappears after 12-14 days and this causes a period. If a pregnancy occurs, then the pregnancy hormone (hCG) keeps the CL alive and its progesterone supports the pregnancy for the next 6-8 weeks until the placenta takes over and the corpus luteum disappears. That means that if the CL is not working correctly there could be problems getting pregnant or staying pregnant. If a CL is not producing enough progesterone it usually means there is a problem with the growing or releasing of the egg and treatment should focus on these areas. In IVF cycles, where normal hormones are switched off, the CL does not produce quite enough progesterone before the pregnancy test and extra progesterone is needed at this time. In recurrent or threatened miscarriage, however, there is not any evidence that the CL is not working well or progesterone is low. However, there is benefit in taking extra progesterone if there is bleeding in early pregnancy in women with previous miscarriages. This might be because of the effects of high-dose progesterone on the womb or immune system. As changes to the hormone environment in pregnancy may have some life-long consequences for the offspring we have to be careful only to give extra progesterone when we are sure it is needed.

Keywords: infertility; luteal phase defect; luteal support; miscarriage; progesterone.

Figure 1

Hormone profile of the menstrual cycle of women. Concentrations of oestradiol and progesterone plotted on the same scale highlighting the dominance of progesterone. Data adapted from Groome et al. (1996), Duncan (2017).

Figure 2

The requirement for luteal support during assisted conception. (A) In a downregulated cycle, exogenous hCG induces progesterone production, but in the absence of LH progesterone output declines earlier than during a natural cycle (dotted line). (B) In a conception cycle, endogenous hCG rises exponentially from LH+7 to maintain progesterone output (dotted line). (C) The endogenous hCG will rescue the corpus luteum in a downregulated cycle in assisted conception to maintain progesterone but there is a time of relative progesterone deficiency in the mid-luteal phase (Duncan 2017).