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endometrial biopsy

Sunday 12 May 2013


To ensure a good specimen for morphologic interpretation, a biopsy sample should be taken from both the anterior and the posterior endometrium and fixed immediately in 10% buffered formalin.

In current practice, the device that is most often used is the Pipelle endometrial aspirator.

To ensure a maximum amount of tissue for morphological reading, the specimen should be placed on a piece of lens paper or some other adhesive tissue and then immersed in the fixative. By this means, all of the tissue fragments remain tightly attached to the lens paper, rather than floating in the fixative, and no tissue will be lost for histologic examination.

In premenopausal women with regular menstrual cycles, histological preparations include the upper portion of the functional layer of the endometrium.

This is necessary, for in most instances morphological changes occur in the functionalis as opposed to the basalis layer, and, by inference, provide a clinically useful diagnosis.

In cases in which little or no tissue is obtained but the endometrium was penetrated with the aspirator, a repeat procedure should be performed.

If the repeat aspiration still yields little tissue, one can assume severe endometrial atrophy or obstructing endometrial polyp.

Taking an endovaginal ultrasonography of the uterus may solve this dilemma.

If the aspirator is ’blocked’ at the lower uterine segment (internal os), traction may be applied on the uterus with either a single-toothed tenaculum or preferably an Emmet tenaculum placed about half a centimetre into the anterior endocervical canal. This will help pass over the area of resistance.

The pathology requisition should contain all pertinent information, including date of last menstrual period.

Endometrial cycle dating

The best way to prove or disprove that ovulation has taken place is to take an endometrial sample on cycle day 22 or later, preferably at the onset of uterine bleeding.

By obtaining samples at the time of early uterine bleeding, the pathologist will be able to determine whether the bleeding is caused by the breakdown of post-ovulatory, secretory endometrium; by focal necrosis of the endometrium associated with anovulation; by other pathologic states; or by hormone administration.

Also, during the period of bleeding, both the external os and the isthmus (lower uterine segment) are widened, facilitating penetration of the biopsy forceps into the endometrial cavity.

The final argument in favor of taking samples at the onset of bleeding is that endometrium of the first 2 days of menstruation is relatively easy to recognize histologically.

In contrast, secretory-phase endometrium often demonstrates subtle changes and, in many cases, combinations of morphologic changes, resulting in most instances in errors of 4–5 days.

The pathologist can improve this to 2–3 days, however, by acquiring expertise in endometrial dating (all cases of normal endometria are to be dated regardless of reasons for sampling), and by basing the dating on those endometrial morphologic alterations that represent the most advanced phase of the menstrual cycle.

For example, if an endometrial biopsy contains changes consistent with post-ovulatory days (POD) 2, 3 and 4, the pathologist should report the diagnosis as ’POD 4 or 18th-day secretory endometrium’ assuming that ovulation has taken place on the 14th day of an idealized endometrial cycle of 28 days total.

In any case, one should not average cycle days and report ’POD 3 or 17th-day secretory endometrium’.

Endometrial biopsies are not to be taken at the onset of bleeding in the following two conditions: if luteal phase defect (LPD) is suspected clinically and is desired to be confirmed histologically, when the biopsy should be taken between POD 7 (21st) and POD 9 (23rd) cycle days to demonstrate a 3–4 day delay in endometrial maturation; or if there are asynchrony of gland/stromal development and dissimilar maturation in different regions of the endometrial specimen.

These changes are presumably due to the poor development of the corpus luteum. According to most investigators, measurements of serum progesterone levels rather than histological dating of the endometrium provide for the best assessment of LPD (see discussion later in this chapter).

In LPD, circulating progesterone levels are decreased and not sufficient to promote full secretory differentiation of the endometrium.

A repeat biopsy taken during the same period of the following cycle will further confirm an abnormally short corpus luteum life span.


- Early Secretory: POD3 - Subnuclear vacuoles and nuclei uniformly aligned.


- The endometrial cycle at GLOW

PDF presentations

- http://medicinemosul.uomosul.edu.iq/files/pages/page_3533746.pdf
- https://www.schulich.uwo.ca/pathol/about_us/pdf/aaron_haig.pdf

Open references

- W G McCluggage. My approach to the interpretation of endometrial biopsies and curettings. 2006. doi : 10.1136/jcp.2005 029702