Luteal Phase Deficiency and Recurrent Miscarriage: What you need to know
Luteal phase deficiency (LPD) is a clinical diagnosis associated with an abnormal luteal phase, often defined by a luteal phase length of less than 10 days. The luteal phase, which occurs after ovulation and before menstruation, is when the corpus luteum produces progesterone, a crucial hormone for preparing the uterine lining for implantation and maintaining early pregnancy.
What Causes LPD?
Several factors can disrupt the normal hormonal balance and lead to LPD:
Inadequate progesterone production or duration: The corpus luteum may not produce enough progesterone or for a sufficient time. Progesterone is released in pulses under the control of luteinizing hormone (LH).
Endometrial resistance to progesterone: The uterine lining may not respond effectively to progesterone.
Underlying medical conditions: Various conditions, such as hypothalamic amenorrhea, eating disorders, excessive exercise, stress, obesity, polycystic ovary syndrome (PCOS), endometriosis, thyroid dysfunction, and hyperprolactinemia, can disrupt the normal hormonal balance. Advancing maternal age can also contribute.
Is LPD a Cause of Infertility or Pregnancy Loss?
This is a controversial topic. While LPD has been linked to infertility and recurrent pregnancy loss, it hasn't been proven to be an independent cause. LPD has also been diagnosed in fertile women with regular menstrual cycles.
Some studies suggest that successful conception cycles have a more rapid rise in progesterone and higher mid-luteal estrogen and progesterone levels. However, other studies have found that luteal phase hormone profiles can be similar whether or not a cycle results in pregnancy or early pregnancy loss.
How is LPD Diagnosed?
There is no single, reliable test to diagnose LPD and distinguish between fertile and infertile women. Proposed diagnostic tests include:
Shortened luteal phase: Usually defined as a luteal phase of less than 10 days. However, short luteal phases can occur in fertile women.
Progesterone levels: There is no established threshold for normal luteal function, as progesterone is secreted in pulses and fluctuates throughout the luteal phase. While a single progesterone level greater than 3 ng/mL indicates ovulation occurred, it is not a sufficient measure for luteal function. Integrated progesterone levels (multiple daily measurements) have not been clinically validated.
Endometrial biopsy: Historically, this was considered the gold standard but it has been shown to be inaccurate and cannot distinguish between fertile and infertile women.
Combined testing: Some have proposed using a combination of a short luteal phase (<10 days) and a mid-luteal progesterone measurement of <10 ng/mL. However, this is not validated.
The RCOG and Luteal Phase Defects in Recurrent Miscarriage
The Royal College of Obstetricians and Gynaecologists (RCOG) also addresses luteal phase defects in the context of recurrent miscarriage. Here's what the RCOG guidelines suggest:
Insufficient/Inconclusive Evidence: The RCOG guidelines note that there is insufficient or inconclusive evidence regarding luteal phase defects.
Midluteal Progesterone: One study found a higher incidence of a luteal phase defect (midluteal progesterone less than 30 nmol/l) in women with recurrent miscarriage versus fertile controls, but another study found no correlation between a luteal phase defect (midluteal progesterone less than 10 ng/ml) and subsequent miscarriage in women with recurrent miscarriage.
Molecular Studies: The RCOG suggests that given the limited and inconsistent data from histological and serological exams during the midluteal phase, molecular studies of the endometrium may prove to be more insightful.
Progestogen Supplementation: The RCOG recommends that progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example, 400 mg micronized vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). This recommendation is based on evidence from the PRISM trial and a review of the PROMISE and PRISM trials which concluded that women with a history of miscarriage who present with bleeding in early pregnancy may benefit from progesterone.
Progesterone supplementation may also reduce miscarriage in women with unexplained recurrent miscarriage, although there is some variability in the data regarding the efficacy of different routes and dosages of progesterone, and these factors may affect outcomes for asymptomatic women
Treatment Options
Due to the lack of clear diagnostic criteria for LPD and the lack of evidence that it causes infertility or recurrent pregnancy loss, treatment is controversial. The first step is to correct any underlying medical conditions.
Ovarian stimulation: Not shown to treat LPD.
Progesterone Supplementation: While progesterone is beneficial after various therapeutic infertility treatments, there is no evidence that it is beneficial for fertility in natural cycles or for treating LPD. However, the RCOG suggests that progestogen supplementation may benefit women with recurrent miscarriage who present with bleeding in early pregnancy.
The Bottom Line
LPD remains a controversial topic with no clear diagnostic criteria or treatment options. More research is needed to determine if LPD is an independent cause of infertility and recurrent pregnancy loss. If so, further research is needed to develop reliable diagnostic tests and effective treatments.
In summary, if you are experiencing infertility or recurrent miscarriage, it’s essential to have a thorough evaluation. If an underlying medical condition is suspected of causing a luteal phase defect, it should be addressed appropriately. Histologic dating of the endometrium with endometrial biopsies is not recommended. The RCOG recommends that progestogen supplementation should be considered for women with recurrent miscarriage who present with bleeding in early pregnancy.