Progesterone deficiency: diagnosis, treatment, and role in infertility

Maintenance of early pregnancy requires progesterone. Progesterone is a hormone produced by the ovary (corpus luteum) in the second half of the menstrual cycle (after ovulation, also called luteal phase) and for the first few weeks of pregnancy. At around seven weeks of pregnancy, the placenta starts producing progesterone.

Removal of the corpus luteum prior to seven weeks of pregnancy will result in a miscarriage. Thus progesterone is very important for implantation and early pregnancy. The question is does progesterone deficiency (also known as luteal phase deficiency, luteal phase defect, or LPD) cause infertility or miscarriage?

My mentor the late Dr Georgeanna Segar Jones initially described LPD in 1949. LPD has been associated with infertility, first trimester pregnancy loss, short cycles and pre-menstrual spotting. Other conditions associated with LPD include eating disorders (anorexia), excessive exercise, stress, obesity and polycystic ovarian disease. Certain hormonal conditions also associated with LPD include thyroid disorders, elevated prolactin levels (hyperprolactinemia) and 21-hydroxylase deficiency. LPD is often seen with ovulation induction especially with the use of gonadotropin-releasing agonists and assisted reproductive technologies (ART).

It has not been established that persistent LPD is a cause of infertility.

Currently the major problem is the lack of a reliable test to diagnose this disorder. Tests that have been used include basal body temperature (BBT) charts, progesterone levels and endometrial biopsy.

BBT charts are seldom used today. They are useful to document ovulation but are inaccurate and inconvenient for patients. The normal luteal phase length is 12 – 14 days. An interval of 8 or fewer days from the time of the LH surge to menstruation is considered as a short luteal phase.

Progesterone is a hormone that is released in pulses and levels may fluctuate up to 8-fold within 90 minutes. Using a single blood progesterone level to assess luteal phase progesterone adequacy is akin to looking out of the window once to determine how much it has rained all day! Progesterone levels peak 6 to 8 days after ovulation. There, however, is no minimum progesterone level that defines “fertile” luteal function. A random progesterone level therefore is not a valid clinical diagnostic tool to diagnose LPD.

An endometrial biopsy was long considered as the “gold standard” for diagnosing LPD. However, recent prospective, blinded clinical trials have shown endometrial biopsies to be imprecise and there were no differences between fertile and infertile women.

If diagnosis is not possible, is treatment for LPD ever appropriate? The answer is yes in certain situations.

If there is any underlying hormonal disorder, it should be corrected (e.g. thyroid, prolactin disorders). Reducing the amount of exercise, weight gain in patients with anorexia and reduction of stress will often correct LPD.

Ovulation induction with clomiphene citrate improves the quality of ovulation. Also, more than one egg may ovulate. Both these factors have been utilized to correct any possible LPD in patients.

Progesterone supplementation is controversial. If used, it should be started 2 -3 days after ovulation. It is not useful in natural cycles, but may used in ovulation induction cycles. In cycles of IVF progesterone supplementation is routinely used.

hCG injections have been used to stimulate the corpus luteum to release more progesterone and thus correct LPD. In IVF cycles, they may increase the incidence of ovarian hyperstimulation syndrome.

In conclusion, progesterone is important for the process of implantation and early pregnancy development. However, LPD as an independent cause of infertility has not been proven.

To see a fertility specialist who is qualified to determine the best course of action when progesterone deficiency may be present, make an appointment at one of InVia's four Chicago area fertility clinics.