Progesterone deficiency: diagnosis, treatment, and role in infertility

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progesterone deficiency diagnosis treatment infertilityMaintenance 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 Fertility’s Chicagoland locations.

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12 Responses to Progesterone deficiency: diagnosis, treatment, and role in infertility

  1. Commenter says:

    Hello Dr Karande,
    Can you help me figure out the meaning of my recent test results:

    I am seeing an RE for recurrent pregnancy loss. I am 38, my AMH is 1.63, My FSH is 5.6. All recurrent loss blood tests came back normal. I have had one successful pregnancy 2 years ago. They are monitoring my progesterone this cycle and here are the results:

    Day 12 – 0.431 (Had an SHG done this day as well and was told I would ovulate in approx. 3 days, based on my follicles during the US)

    Day 22 – 8.94
    Day 25 – 12.2

    When the nurse called me after my day 22 results, she said that my progesterone was low. We did another test a few days later and she now says that it’s fine, that I probably just ovulated later than expected.

    Do these number tell you anything significant? Is that 12 still on the lower end of normal? My last miscarriage was marked with low progesterone.

    They also ran my E2 levels, which were:

    Day 2 – 42.8
    Day 12 – 69.5

    I don’t know if they are relevant, but the nurse also mentioned that the Estrogen level was a little low for my Day 12 test.

    Does this indicate a bad egg or possible luteal phase defect? You mention that Progesterone Supplements are not useful in a natural cycle. I do not plan to be on any fertility meds yet (I get pregnant naturally every time, I just can’t maintain the pregnancy) but my RE wants to start progesterone therapy as a precautionary measure. Will that do anything, since I’m not inducing ovulation?

    Thank you!

    • You can start progesterone in your particular situation.
      Another way would be to take clomiphene citrate 100 mg (2 tablets) from day 5-9 of the cycle. Monitor for color change with an urinary LH kit. Have an ultrasound and bloods (E2/P/LH) the day after color change. If there indeed are pre-ovulatory follicles, ovulation can be trigered with hCG 10,000 iu. This shot would also boost progesterone production by the corpus luteum.

      Good luck!
      DR V Karande

  2. Commenter says:

    Is there way we can select gender.
    Kindly suggest for male conception

  3. Commenter says:

    Kindly suggest for male conception

    Is there way we can select gender

  4. Commenter says:

    How to conceive male child

  5. Commenter says:

    Hi Dr Karande,
    My wife had failed ivf last cycle and this cycle she is pregenent naturally. Her hcg is 1999 and progesterone is low 4.01. Is progesterone level a concern? our clinic prescribed only one 100mg suppository for progesterone once a day. While on ivf cycle – it was prescriobed as 3 times a day. can you please suggest if any other precaution also needed?


  6. Commenter says:

    Hi Doctor. Your website is very helpful.
    I am 44.
    I have FSH 6.2
    AMH .5
    estrogen 460
    no thyroid problem.

    I have had three preg. one over 10yrs ago (abortion)
    Second – 11 wks and 5days miscarriage.
    Third – 6 wks miscarriage

    I have had 2 follicles and 3 follicles in each ovary.

    I suspect (not sure why) that my progesterone is low.

    My second preg I had a heart beat and felt great…no major pregnancy symptoms beside body changes. The third preg..same as well just body changes but no vomiting and such. My HCG level was slow rising last time. at 4wks 1147. At 4weeks 1513 at 5wks 2500 at the miscarriage at 6wks at 3300.

    I am trying naturally. I only take prenatal. I am otherwise a healthy individual.

    do you think I should demand progesterone for the next try?

    • I am sorry to hear about your miscarriages.
      The miscarriage rate in your age group is around 50%. The reason the miscarriage rate is so high is because of the pregnancy being chromosomally abnormal — usually due to egg quality.
      It is okay for you to ask for progesterone with your next try.
      It will probably not make a difference but will not hurt.
      We have been able to help many patient in your situation with donor eggs.
      Dr V Karande

  7. Commenter says:

    This information is very useful an going to help so many members and they will be happy….

About Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.

View all posts by Dr. Vishvanath Karande →

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