eMedicine Specialties > Obstetrics and Gynecology > Reproductive Endocrinology and Infertility

Luteal Phase Dysfunction: Differential Diagnoses & Workup

Author: Thomas L Alderson, DO, Program Director, Assistant Professor, Department of Obstetrics and Gynecology, Mount Clemens Regional Medical Center, Michigan State University College of Osteopathic Medicine
Contributor Information and Disclosures

Updated: Oct 8, 2008

Differential Diagnoses

Hyperprolactinemia
Polycystic Ovarian Syndrome
Thyroid Disease

Workup

Laboratory Studies

  • Serum progesterone levels have been studied as a means to diagnose luteal phase deficiency (LPD). Early data showed that peak progesterone production occurred in the mid-luteal phase. Later studies confirmed that progesterone is released in a pulsatile fashion, suggesting that a single sample is nondiagnostic. The use of multiple samples to overcome the pulsatile nature of progesterone is expensive and inconvenient.
  • Urinary LH kits provide a useful test to estimate the appropriate timing of an endometrial biopsy (EB). Following a positive test finding, ovulation occurs within 24-26 hours. The EB should be performed on the 12th day of a 14-day luteal phase.
  • Studies measuring progestin endometrial protein (PEP) have not been conclusive in diagnosing LPD. Studies regarding cell adhesion molecules or integrins, growth factors, and cytokines are all in the experimental phase.

Imaging Studies

Ultrasound documentation of ovulation from follicular growth to collapse of the follicle is very accurate; however, this procedure is too expensive and time consuming to be realistic in all patients. Ultrasound measurement of endometrial thickness has not been shown to be effective in the prediction of luteal phase deficiency.

Procedures

  • Biopsy
    • In 1950, Noyes, Hertig, and Rock established that the diagnosis of luteal phase deficiency (LPD) is centered on histologic dating of the endometrium. However, the location and time of the biopsy can greatly influence endometrial biopsy (EB) findings. Some authors believe that mid-luteal phase biopsy is the best for accurate diagnosis of LPD.
    • Biopsies from the fundus of the uterus yield improved histologic samples compared to those taken from the lower uterine segment. Specimens taken approximately 1-2 days prior to menses provide better specimens for interpretation. For example, women with cycles of 28 days should have an EB performed on the 26th day.
    • Histologically, a luteal phase defect provides a biopsy that lags behind the date of actual endometrial sampling by 3 days or more. To confirm that such a result is not a variance within the reference range, the biopsy should be performed in 2 consecutive cycles; however, the discomfort associated with the biopsy causes difficulty in convincing the patient to have the procedure performed twice. Several methods can be used to time the EB just prior to menses. The basal body temperature (BBT) chart is one such method.
      • The BBT chart can aid in determining the length of the luteal phase. A luteal phase of less than 11 days may be associated with LPD.
      • The BBT chart can also assist in timing the EB by observing the patient's cycle length and performing the biopsy 2 days prior to the expected menses.
      • Although the BBT chart is easy and inexpensive, interpretation can be difficult and frustrating with a woman who is infertile or has suffered multiple pregnancy losses.

More on Luteal Phase Dysfunction

Overview: Luteal Phase Dysfunction
Differential Diagnoses & Workup: Luteal Phase Dysfunction
Treatment & Medication: Luteal Phase Dysfunction
Follow-up: Luteal Phase Dysfunction
References
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References

  1. Behrman HR, Endo T, Aten RF. Corpus luteum function and regression. Reprod Med Rev. 1993;2:153-80.

  2. Cermik D, Selam B, Taylor HS. Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab. Jan 2003;88(1):238-43. [Medline].

  3. Cicinelli E, de Ziegler D, Bulletti C, et al. Direct transport of progesterone from vagina to uterus. Obstet Gynecol. Mar 2000;95(3):403-6. [Medline].

  4. Cooke ID. The corpus luteum. Hum Reprod. Feb 1988;3(2):153-6. [Medline].

  5. Csapo AI, Pulkkinen MO, Ruttner B et al. The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies. Am J Obstet Gynecol. Apr 15 1972;112(8):1061-7. [Medline].

  6. Daftary GS, Taylor HS. Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression. Fertil Steril. Sep 2002;78(3):577-80. [Medline].

  7. Giudice LC. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine. Fertil Steril. Jan 1994;61(1):1-17. [Medline].

  8. Healy DL, Schenken RS, Lynch A, et al. Pulsatile progesterone secretion: its relevance to clinical evaluation of corpus luteum function. Fertil Steril. Jan 1984;41(1):114-21. [Medline].

  9. Jones GES. Some newer aspects of management of infertility. JAMA. 1949;141:1123-1129.

  10. Jones GS. The luteal phase defect. Fertil Steril. Apr 1976;27(4):351-6. [Medline].

  11. Karamardian LM, Grimes DA. Luteal phase deficiency: effect of treatment on pregnancy rates. Am J Obstet Gynecol. Nov 1992;167(5):1391-8. [Medline].

  12. Li TC, Nuttall L, Klentzeris L, Cooke ID. How well does ultrasonographic measurement of endometrial thickness predict the results of histological dating?. Hum Reprod. Jan 1992;7(1):1-5. [Medline].

  13. McNeely MJ, Soules MR. The diagnosis of luteal phase deficiency: a critical review. Fertil Steril. Jul 1988;50(1):1-15. [Medline].

  14. Murray DL, Reich L, Adashi EY. Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study. Fertil Steril. Jan 1989;51(1):35-41. [Medline].

  15. Noyes RW, Hertig AW, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3-25.

  16. Peters AJ, Lloyd RP, Coulam CB. Prevalence of out-of-phase endometrial biopsy specimens. Am J Obstet Gynecol. Jun 1992;166(6 Pt 1):1738-45; discussion 1745-6. [Medline].

  17. Peters AJ, Wentz AC. Luteal phase inadequacy. Seminars in Reprod Endo. 1995;13:162-171.

  18. Sherman BM, Korenman SG. Measurement of plasma LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the short luteal phase. J Clin Endocrinol Metab. Jan 1974;38(1):89-93. [Medline].

  19. Shoupe D, Mishell DR Jr, Lacarra M, et al. Correlation of endometrial maturation with four methods of estimating day of ovulation. Obstet Gynecol. Jan 1989;73(1):88-92. [Medline].

  20. Soules MR. Luteal phase deficiency. In: Pitkin RM, ed. Clinical Obstetrics and Gynecology. Vol 34. Philadelphia, PA: JB Lippincott; 1991:123-126.

  21. Taylor HS, Bagot C, Kardana A, et al. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. May 1999;14(5):1328-31.

  22. Yen SC, Jaffe RB, Barbieri RL. Luteal phase defects. In: Reproductive Endocrinology. 4th ed. 1999:244-5.

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Further Reading

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Keywords

luteal phase dysfunction, LPD, luteal phase deficiency, luteal phase defect, progesterone, infertility, recurrent pregnancy loss

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Contributor Information and Disclosures

Author

Thomas L Alderson, DO, Program Director, Assistant Professor, Department of Obstetrics and Gynecology, Mount Clemens Regional Medical Center, Michigan State University College of Osteopathic Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital, Mammoth Lakes, California, Pioneer Valley Hospital, Salt Lake City, Utah, Warren General Hospital, Warren, Pennsylvania and Mountain West Hospital, Tooele, Utah
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Bryan D Cowan, MD, Professor and Chairman, Department of Obstetrics and Gynecology, University of Mississippi College of Medicine; Consulting Staff, Department of Obstetrics and Gynecology, Veterans Affairs Medical Center; Medical Director, Wiser Hospital for Women, University of Mississippi Medical Center
Bryan D Cowan, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Gynecological and Obstetrical Society, American Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Endocrine Society, Sigma Xi, Society for Assisted Reproductive Technologies, Society for Gynecologic Investigation, Society for the Study of Reproduction, and Society of Laparoendoscopic Surgeons
Disclosure: Galil None Consulting

 
 
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