The menstrual cycle has two roughly equal parts that are divided by ovulation. The first (preovulatory) is the proliferative (follicular) phase which is characterized by the growth and development of at least one “dominant” ovarian follicle that produces the hormone estrogen that promotes growth and development of the uterine lining (endometrium). The second is the the secretory (luteal) phase. It commences with the release of one or more eggs by the dominant follicle(s) and is characterized by the conversion of the ruptured dominant follicle into a “yellow structure” known as the corpus luteum (CL). In addition to estrogen, the CL produces progesterone hormones which causes the endometrial gland to produce secretions that are intended to nurture the early implanting embryo as it sends its root system (trophoblast) into the uterine lining as it strives to makes contact with the mother’s blood system.

In regularly ovulating women, the menstrual cycle is usually quite regular in length, ranging from 26-32days. However, this can vary somewhat and when it does, it is usually the proliferative (follicular) phase that is shortened or lengthened. The secretory (luteal) phase is usually quite constant and regular in duration, rarely varying by more than a day or two in length. The role of CL hormones is to prepare the uterine lining to accept and support the implanting embryo during the first 8 weeks of pregnancy whereupon the embryo’s “root system” (that ultimately develops into the placenta), takes over hormone production completely from the ovary. In fact, by the 9th to 10th week, even were both ovaries to be surgically removed, the pregnancy would continue to develop autonomously. This also serves to explain why in embryo recipient cycles (frozen embryo transfers, egg donor IVF etc.), where hormones must be administered because the ovaries do not contribute hormones to the developing embryo, hormone supplementation can be discontinued after the 10th week of pregnancy.

The life span of the CL determines the length of the secretory (luteal) phase. It survives for 12-13 days, unless rescued by the early release of hCG from the implanting embryo. If no implantation occurs, the CL stops making estrogen and progesterone, and menses will usually ensue 1-3 days later.

As stated above, for most women, the length of the second half of the menstrual cycle is constant at 13-14 days. In a small percentage of infertile women (3-5%), hormone production by the CL is compromised and/or the length of the secretory (luteal) phase is shortened by more than 3 or 4 days. This often results in inadequate endometrial secretory development – referred to as a luteal phase defect (LPD). In some cases, this prevents embryo attachment altogether (resulting in “infertility”) while in other cases it can result in early miscarriage due to insufficient hormonal support for the “budding” pregnancy.

The lining of the uterus has a specific appearance that changes throughout the menstrual cycle. Because of this fact, a biopsy of the lining a few days prior to expected menstruation can accurately date endometrial development and hence the potential of the secretory endometrium to support implantation. A difference of more than 3 days between endometrial dating by biopsy and dating by cycle day (as determined by the start of the preceding menstrual period) is highly suggestive of a luteal phase defect (LPD). In addition, a blood progesterone level of less than 10ng/dl a week after ovulation can also be used to diagnose a LPD.

In the past, LPDs were traditionally treated through progesterone administration in the secretory (luteal) phase of the cycle and continued though the first 12 weeks of pregnancy (the 1st trimester). However, since all LPDs begin with a poor proliferative (follicular) phase and inadequate dominant follicle development, it follows that such an approach represents an over-simplification of the problem. What is needed is reinstitution of normal follicular development with ovulation induction using oral fertility drugs such as clomiphene and Letrozol, or injectable gonadotropins such as Menopur, Follistim or Gonal F, followed by hCG to trigger ovulation. Thereupon, progesterone or hCG supplementation can be added until the 8th-9th week of pregnancy.

Sadly, the diagnosis of LPD is often missed. This is yet another example of where the term “unexplained infertility or miscarriage” should be supplanted by “undiagnosed reproductive failure.”