Luteal Phase Deficiency- does it exist? Can it be treated?

Posted January 22, 2015 by Claire

Background:

• Progesterone, released by the corpus luteum after ovulation, is essential for implantation and maintenance of pregnancy until placental function is established.
• Luteal phase deficiency (LPD) has been described as a condition in which a female’s own progesterone is not sufficient either for normal implantation or to sustain an otherwise normal pregnancy.
• LPD theoretically may be associated with:
  • Shortened menstrual cycles
  • Premenstrual spotting
  • Infertility
  • First trimester pregnancy loss
• Luteal phase function may be impacted by the following medical conditions:
  • Ovarian aging
  • Anorexia, eating disorders, or significant weight loss
  • Recovery from hypothalamic amenorrhea
  • Thyroid dysfunction
  • Hyperprolactinemia
  • Obesity
  • PCOS
  • Endometriosis
• Controversy exists whether LPD alone (independent of the above disorders) results in single or recurrent pregnancy loss, or whether the issue is related to egg quality or other underlying dysfunction.

How is luteal phase deficiency diagnosed?

• No reliable test exists to diagnose this disorder.
• Progesterone levels are secreted in pulses, meaning that a low level on a test may or may not be significant.
• Endometrial biopsies are NOT able to reliably distinguish normal endometrial phase of development from LPD and have wide variability, and therefore are not used in evaluation.
• Measurement of basal body temperature (BBT) is inaccurate and is discouraged.
• Cycle length may provide insight into LPD. The number of days from LH surge (ovulation predictor kits) to the start of menses is typically 13 to 15 days, or from ovulation to menses: 12 to 14 days. Time <12 days from LH surge to menses is considered abnormal (<11 days from ovulation).
• Laboratory evaluation for underlying disorders affecting the menstrual cycle should include:
  1. FSH and LH levels
  2. TSH and PRL

If LPD is suspected, what treatments are available?

1. Correction of underlying disorders as above (eating disorders, hypothalamic amenorrhea, thyroid dysfunction, hyperprolactinemia.)
2. Ovarian stimulation with clomiphene citrate or letrozole may improve pre-ovulatory follicular dynamics and therefore improve corpus luteum function. (Alternatively, use of such agents that induce ovulation may improve fertility simply by inducing multiple follicles to ovulate- resulting in multiple eggs released- and multiple corpus luteum.) *Monitoring during a cycle of stimulation is essential to determine (over- or under-) response to the medication and to reduce the risk of multiple gestation.
3. hCG “trigger shot” to ensure ovulation and stimulate corpus luteum progesterone production.
4. Progesterone support of the luteal phase.
   • Infertility: There is no evidence that progesterone supplementation alone improves pregnancy outcomes during normal (unmedicated) cycles.
   • Recurrent Pregnancy Loss (RPL): Although controversial, meta-analyses of available trials show a benefit of progesterone supplementation in patients with unexplained RPL (after exclusion of other causes for RPL).
     1. Vaginal progesterone avoids metabolism by the liver and increases uterine concentrations compared to oral administration.
     2. May be prescribed as progesterone 200mg twice-three times daily, progesterone in gel, 90mg daily, or micronized progesterone, 100mg, 2-3x daily
     3. Begin 3 days after the LH surge (to prevent interference with ovulation) and continue through 8-10 weeks gestation.

 Does treatment pose any risks to me or my pregnancy?

• The available evidence indicates that most common forms of progesterone supplementation during early pregnancy pose no significant risk to mother or fetus.
• Side effects of progesterone therapy include nausea and fatigue.
• Progesterone therapy may delay menses; in conjunction with the above side effects, you may “feel” pregnant. Therefore, it is important to check a urine or serum pregnancy test to detect pregnancy.
• Progesterone will not support a pregnancy that was otherwise (naturally) going to miscarry due to an abnormality.

Conclusions:

• Abnormal luteal function may occur as the result of a medical condition (above) and infertile women should be investigated for these disorders, and treated appropriately.
• LPD as an independent cause of infertility has not been proven.
• No diagnostic test for LPD has been proven reliable in a clinical setting.
• No treatment for LPD has been shown to improve pregnancy outcomes in natural, unstimulated cycles for infertility.
• The use of ovulation-induction agents (in conjunction with IUI) for unexplained infertility is appropriate and plausibly improves luteal function by improving pre-ovulatory follicular development.
• Whether luteal phase support improves outcomes in patients with unexplained RPL is controversial, but with low risks of therapy and limited side affects, in conjunction with potential benefit seen in small studies, such therapy may be appropriate.

 

More information from the American Society for Reproductive Medicine may be found at ReproductiveFacts.org