The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies

Owen K. Davis; Alan S. Berkeley; Gregory J. Naus; Ina N. Cholst; Karen S. Freedman

doi:10.1016/s0015-0282(16)60603-9

Menstrual Cycle Cycle Disorders

The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies

Davis OK, Berkeley AS, Naus GJ, Cholst IN, Freedman KS

Published April 1989 Fertility and Sterility, 51(4), 582-586

DOI 10.1016/s0015-0282(16)60603-9 PMID 2924928

RRM Academy Synopsis

Fertile women had out-of-phase biopsies in the infertile-patient range

This 1989 study followed five women with proven fertility through 35 single endometrial biopsies and 30 consecutive pairs. Luteal phase defect on biopsy appeared at rates in the range reported for infertile patients. Of 35 single biopsies, 11 lagged 3 days or more. Of 30 back-to-back pairs, 2 did.

Key Findings

Five regularly menstruating women of proven fertility had 39 endometrial biopsies. After four exclusions, the analysis used 35 single biopsies and 30 consecutive pairs.
At a lag of 2 days or more, 18 of 35 single biopsies (51.4%; 36.6% to 71.2%) and 8 of 30 consecutive pairs (26.7%; 12.3% to 45.9%) were out-of-phase.
At a lag of 3 days or more, 11 of 35 single biopsies (31.4%; 16.9% to 49.3%) and 2 of 30 consecutive pairs were out-of-phase. No subject had three consecutive out-of-phase biopsies.
In the authors' infertility practice, 15 of 73 first biopsies (20.5%) lagged over 2 days, as did 1 of 5 repeats (20%). They estimated an LPD incidence of 4.1%.
One woman had 4 of 6 single biopsies out-of-phase at a lag of 3 days or more. She became pregnant in her seventh biopsy cycle and delivered at term without complications.

Interpretation

This cohort study followed five women with proven fertility for up to ten monthly biopsies each. The authors suggest that an immature biopsy, even in a consecutive pair, can be a normal variant in a fertile woman. They stress that ovulatory dysfunction can still cause infertility. They question only the diagnostic standard built on single or paired out-of-phase biopsies. The authors note that because they treated each biopsy as an independent data point, their confidence limits are preliminary. The findings support larger studies of how well biopsy timing can separate normal variation from true luteal phase defect.

RRM Context

Restorative reproductive medicine charts the cycle and looks for a cause before treating. The authors ask whether two out-of-phase biopsies tell a normal variant apart from real disease. One woman's biopsy lag ranged from 0 to 8 days across six dated biopsies, and she later conceived. The authors calculate that treatment started after two out-of-phase biopsies could show a high success rate on the next biopsy by chance alone.

Our editorial summary of this paper, not the article's abstract.

Abstract

Five regularly menstruating women of proven fertility, with normal prolactin and thyroid function studies, underwent a total of 39 endometrial biopsies (EMBs). The slides were dated in blinded fashion, and the cycle date determined by considering the date of the next menstrual period as day 28 and counting backward. Using a 2-day or greater lag in endometrial maturity to define a luteal phase defect (LPD), the incidence of single and sequential out-of-phase EMBs was 51.4% and 26.7%, respectively. Using a 3-day or greater lag to define a LPD, the incidence of single and sequential out-of-phase EMBs was 31.4% and 6.6%, respectively. These incidences in normal, fertile women are as high as the rates quoted for infertile populations, and call into question the standard criteria for defining this condition and evaluating therapies to correct it.

Topics

Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances · Diagnostics › Endometrial Assessment › Luteal Phase Biopsy · Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency

Owen K. Davis, Alan S. Berkeley, Gregory J. Naus, Ina N. Cholst, Karen S. Freedman

O Davis, A Berkeley, Greg Naus, G Naus, I Cholst, K Freedman

PMID 2924928 2924928 DOI 10.1016/s0015-0282(16)60603-9 10.1016/s0015-0282(16)60603-9 Davis et al. 1989, Davis 1989

Keywords

Adult, Biopsy, Endometrium/pathology, Female, Humans, Infertility, Female/pathology, Luteal Phase, Pregnancy

The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies

Fertile women had out-of-phase biopsies in the infertile-patient range

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords