NORMAL ENDOMETRIUM AND

INFERTILITY EVALUATION
DR.M. Saraswathi MD (PATH).,
DGO.,

NORMAL ENDOMETRIUM &

INFERTILITY EVALUATION

HISTOLOGICAL FEATURES OF A NORMAL ENDOMETRIUM

CHANGES WITH A WOMANS AGE THROUGH PREMENARCHAL,
REPRODUCTIVE ,PERI MENOPAUSAL AND POST MENOPAUSAL
YEARS.

DURING REPRODUCTIVE AGE GROUP THE CYCLICAL

HORMONAL CHANGES IN THE MENSTRUAL CYCLE GIVES A
CHANGING MORPHOLOGICAL PATTERN THAT IS NORMAL, SO
IN A BIOPSY SPECIMEN WITH THESE CHANGES AND WITH
ARTIFACTS AND LIMITED SAMPLING EVEN NORMAL PATTERNS
MAY BE DIFFICULT TO INTERPRET.

SECRETORY PHASE IS CONSTANT IN THE NORMAL

CYCLE LASTING 14 DAYS FROM THE TIME OF
OVULATION TO THE ONSET OF MENSTRUATION.

VARIATION IN LENGTH OF THE CYCLE OCCURS

BECAUSE PROLIFERATIVE PHASE VARIES BETWEEN
CYCLES AND BETWEEN WOMEN.

BIOPSY IS TIMED IN THE MID TO LATE LUTEAL PHASE.

BIOPSY HELPS TO CONFIRM THAT OVULATION HAS

OCCURRED AND WHETHER THERE WAS SUFFICIENT
SECRETORY EFFECT DURING THE LUTEAL PHASE.

GYNAECOLOGIST COMPARES THE HISTOLOGICAL DATE TO

THE CLINICAL DATA INCLUDING DATE OF RISE IN BASAL
BODY TEMPERATURE, TIME OF SERUM LH SURGE,
TRANSVAGINAL USG EVALUATION OF FOLLICULAR AND
CORPUS LUTEUM DEVELOPMENT AND SERUM
PROGESTERONE LEVEL OR SUBTRACTION OF 14 DAYS
FROM THE ONSET OF MENSTRUATION.

HISTOLOGICAL
EVALUATION

IDENTIFICATION OF THE SURFACE EPITHELIUM FOR

ORIENTING THE UNDERLYING GLANDS AND STROMA
IS ESSENTIAL.

IN PROLIFERATIVE PHASE THE GLANDS ARE

REGULARLY PLACED IN A PERPENDICULAR
ARRANGEMENT FROM BASALIS TO SURFACE
EPITHELIUM.

IN THE SECRETORY PHASE THEY ARE TORTUOUS, BUT

A THIN REGION BENEATH THE SURFACE- STRATUM
COMPACTUM WHERE THE STROMA IS DENSE AND THE
GLANDS ARE NARROW AND STRAIGHT

STRATUM BASALIS CLOSE TO THE MYOMETRIUM

SHOWS IRREGULARLY SHAPED INACTIVE GLANDS,
DENSE STROMA, AGGREGATES OF SPIRAL ARTERIES
WITH THICKER MUSCULAR WALLS

BIOPSY FROM LOWER UTERINE SEGMENT SHOWS

SHORTER POORLY DEVELOPED INACTIVE GLANDS
WITH A FIBROBLAST LIKE STROMAL CELLS WITH
MORE ABUNDANT CYTOPLASM THAN THE OVAL TO
ROUND STROMAL CELLS WITH SCANT CYTOPLASM OF
CORPUS.

SURFACE EPITHELIUM, A THIN LAYER BENEATH THE

SURFACE EPITHELIUM-STRATUM COMPACTUM,
STRATUM BASALIS, BIOPSY FROM THE LOWER
UTERINE SEGMENT- ALL THESE ARE LESS RESPONSIVE
TO THE HORMONE CHANGES.

SIGNIFICANCE OF SURFACE EPITHELIUM- DUE TO

ESTROGENIC STIMULATION SHOWS A CILIATED
COLUMNAR EPITHELIUM WHICH IS MORE
PRONOUNCED IN PATHOLOGICAL CONDITIONS LIKE
ENDOMETRIAL HYPERPLASIA/METAPLASIA.

DATING OF THE NORMAL

ENDOMETRIUM

NORMAL ENDOMETRIUM HAS 2

PHASES
PROLIFERATIVE PHASEESTRADIOL BY THE GRANULOSA
CELL OF THE OVARIAN
FOLLICLE.

SECRETORY PHASE
(LUTEAL/POST
OVULATORY) COMBINED EFFECT OF
ESTRADIOL &
PROGESTERONE BY
LUETINISED
GRANULOSA & THECA
CELLS OF CL.

HISTOLOGICAL DATING
IS MORE PRECISE IN
THE POST OVULATORY
PHASE AS CHANGES
ARE DISCRETE IN IT

KEY HISTOLOGICAL FEATURES

GLAND AND STROMA
GLANDULAR CHANGES

1.
2.
3.

4.
5.

TORTUOSITY
GLAND MITOSIS
ORIENTATION OF NUCLEI
(PSEUDO STRATIFICATION
VS BASAL)
BASAL SUBNUCLEAR
CYTOPLASMIC VACUOLES
LUMINAL SECRETIONS
WITH SECRETORY
EXHAUSTIONS.

STROMAL CHANGES

1.
2.
3.
4.

EDEMA
MITOSIS
PREDECIDUAL
CHANGE
INFILTRATION OF
GRANULAR
LYMPHOCYTES

PROLIFERATIVE PHASE
- EARLY ( 4TH TO 7TH DAY )
SURFACE

EPITHELIUM THIN
GLANDS SMALL &
TUBULAR
EPITHELIAL MITOSIS
+
STROMA COMPACT
& DENSE MITOSIS +

MID PROLIFERATIVE PHASE

( 8TH TO 10TH DAY)
COLUMNAR

SURFACE
EPITHELIUM
GLANDS LONG &
CURVED
STROMAL EDEMA +
MITOSIS +

LATE PROLIFERATIVE PHASE

( 11TH TO 14TH DAY )
TORTUOUS

GLANDS
PSEUDOSTRATIFIED NUCLEI
STROMAL MITOSIS +
MODERATELY DENSE
STROMA
REGULAR SPACING &
UNIFORM SHAPE OF THE
GLANDS & ORIENTATION TO
THE SURFACE EPITHELIUM
IS PERPENDICULAR AND
REGULAR.

INTERVAL ENDOMETRIUM
( 14TH AND 15TH DAY )
COILED

ENDOMETRIAL
GLANDS
MITOTIC FIGURES STILL
PRESENT IN
ENDOMETRIAL GLANDS
SUBNUCLEAR VACUOLES
IN <50% OF GLANDS
PRESENCE OF VACUOLES
IS DUE TO PRESENCE OF
GLYCOGEN WHICH IS
DISSOLVED DURING
TISSUE PROCESSING

SECRETORY PHASE
EARLY- ( 16TH TO 20TH DAY ) GLANDULAR CHANGES PREDOMINATE, MID TO
LATE SECRETORY PHASE
( 21ST TO 27TH DAY) STROMAL CHANGES
PREDOMINATE

17TH

DAY REGULAR
VACUOLATION > 50%
OF THE GLANDS
SHOW SUBNUCLEAR
VACUOLATION.

18TH

DAYVACUOLES
DECREASED IN
SIZE, EARLY
LUMINAL
SECRETIONS
SEEN,BASALLY
PLACED
NUCLEUS

 19TH

DAYFEW VACUOLES
REMAIN,INTRALUMINAL
SECRETION +,NO
PSUEDO
STRATIFICATION,NO
MITOSIS

 20TH

DAY- PEAK OF
INTRALUMINAL
SECRETIONS

 21ST

DAY MARKED
STROMAL EDEMA

 22ND

DAY PEAK
OF STROMAL
EDEMA AND
STROMAL CELLS
HAVE NAKED
NUCLEI

 23RD

DAY
PERIARTERIOLAR
PREDECIDUAL
CHANGE, SPIRAL
ARTERIES
PROMINENT

 24TH

DAY MORE
PROMINENT
PREDECIDUAL
CHANGE , STROMAL
MITOSIS RECUR

 25TH

DAY
PREDECIDUAL
DIFFERENTIATION
BEGINS UNDER THE
SURFACE
EPITHELIUM,
INCREASE IN NO. OF
GRANULAR
LYMPHOCYTES.

 26TH

DAY
PREDECIDUA
STARTS TO BECOME
CONFLUENT

 27TH

DAY
NUMEROUS
GRANULAR
LYMPHOCYTES,
CONFLUENT SHEETS
OF PREDECIDUA,
FOCAL NECROSIS.

 24TH

TO 27TH DAY
TORTOUS WITH
SAW TOOTHED
GLANDS
SECRETORY
EXHAUSTION OF
THE GLANDS,
RAGGED LUMINAL
BORDERS

 28TH

DAY
INITIAL EVIDENCE OF
STROMAL
HEMORRHAGE
PROMINENT
STROMAL
GRANULOCYTES
FOCAL THROMBOSIS
IN ENDOMETRIAL
VESSELS
PROMINENT
APOPTOSIS IN
ENDOMETRIAL
GLANDS

MENSTRUAL
ENDOMETRIUM
GLANDULAR

& STROMAL BREAKDOWN

FIBRIN THROMBI IN THE SMALL VESSELS
CONDENSED & COLLAPSED STROMA
NECROTIC DEBRI
NEUTROPHILIC INFILTRATE
THIS PHASE IS NOT GOOD FOR EVALUATION
OF STROMAL & GLANDULAR DEVELOPMENT
IF THE BREAKDOWN IS EXTENSIVE. IF AT ALL
YOU CAN DO IT AT THE ONSET OF BLEEDING

MENSTRUAL
ENDOMETRIUM

PITFALLS IN DATING

ABSENCE OF SURFACE EPITHELIUM

COMPROMISES THE INTERPRETATION

TISSUES FROM LOWER UTERINE SEGMENT

OR BASALIS IS NOT SATISFACTORY FOR
DATING

STRAIGHT TUBULAR GLANDS BENEATH THE

SURFACE ARE NORMAL AND NOT A SIGN OF
IRREGULARITY IN MATURATION IN LATE
SECRETORY PHASE

SCATTERED SUBNUCLEAR VACUOLES NOT

SUFFICIENT FOR EVIDENCE OF OVULATION

PRESENCE OF SECRETION IN THE GLANDULAR LUMEN

DOESNT INDICATE SECRETORY PHASE. PROLIFERATIVE
HYPERPLASTIC AND NEOPLASTIC GLANDS CAN CONTAIN
LUMINAL SECRETIONS

FOCAL GLANDULAR CROWDING CAN OCCUR IN

TANGENTIAL SECTIONING OF BOTH PROLIFERATIVE &
SECRETORY ENDOMETRIUM

FOCAL CYSTIC GLANDS OR NON REACTIVE GLANDS CAN

OCCUR IN NORMAL ENDOMETRIUM

PATCHY STROMAL EDEMA OF 17TH AND 18TH DAY

DOESNT SIGNIFY IRREGULAR MATURATION

COMPACT PREDECIDUA WITH SPINDLE SHAPED STROMAL

CELLS IS NOT A TRUE PREDECIDUAL REACTION,
PREDECIDUA AROUND THE SPIRAL ARTERIOLES IS A MUST

LYMPHOCYTES & GRANULAR LYMPHOCYTES BECOME

PROMINENT IN THE LATE SECRETORY PHASE ( IT IS NOT
INFLAMMATION)

IF TISSUE IS DIFFICULT TO DATE BECAUSE OF APPARENT

DISCORDANCE IT FEATURES POSSIBILITY OF CHRONIC
ENDOMETRITIS OR POLYP

ENDOMETRIUM CANNOT BE DATED ACCURATELY WHEN

POLYPS, INFLAMMATION OR OTHER ABNORMALITIES ARE
PRESENT

ARTIFACTS & CONTAMINANTS

1. TISSUE FRAGMENTATION- GLANDS GET
DETACHED FROM STROMA AND ORIENT
CLOSE TO EACH OTHER
2. CERVICAL EPITHELIUM IN CLOSE
OPPOSITION TO ENDOMETRIUM GIVES A
CONFUSING PATTERN (STROMA HELPS IN
DIFFERENTIATION

TELESCOPING OF GLANDS
GLAND IN GLAND, BOTH IN
PROLIFERATIVE & SECRETORY
PHASE

CONTAMINATION FROM
CERVIX- STRIPS OF BLAND
SQUAMOUS OR MUCINOUS
EPITHELIUM AND POOLS OF
MUCIN & INFLAMMATORY
CELL COLLECTIONS

FRAGMENTS OF ADIPOSE
TISSUE, COLONIC MUCOSAPERFORATION OF THE
UTERUS

LUTEAL PHASE DEFECT & ABNORMAL

SECRETORY PHASE PATTERNS
LPD

IS A RECOGNISED CAUSE OF
OVULATORY INFERTILITY 5% OF CASES

IT

CAN BE A FACTOR IN EARLY HABITUAL

SPONTANEOUS ABORTION & IN ABNORMAL
UTERINE BLEEDING

IT

IS THE RESULT OF HYPOTHALAMIC OR

PITUITARY DYSFUNCTION THAT CAUSES
DECREASED FSH IN THE FOLLICULAR
PHASE.

 ABNORMAL

LH SECRETION & DECREASED LEVELS OF

LH & FSH AT THE TIME OF OVULATION OR ELEVATED
PROLACTIN LEVELS

HYPOTHYROIDISM

CAN ALSO LEAD TO LPD

MONITORING

MID LUTEAL PHASE PROGESTERONE

LEVELS CAN BE EFFECTIVE

HISTOLOGICALY

IT LAGS BY MORE THAN 2 DAYS FROM

THE ACTUAL DATE IN 2 CONSECUTIVE BIOPSIES

BBT,

TIME OF LH SURGE OR THE ONSET OF MENSES

AFTER BIOPSY ESTABLISHES THE DIAGNOSIS

LPD CAN CAUSE DISCORDANCE IN THE DEVELOPMENT

OF GLANDS AND STROMA

-IRREGULAR MATURATION PATTERN WITH DIFFERENT

AREAS SHOWING A MARKED VARIATION OF MORE THAN
4 DAYS (PROLIFERATIVE STROMA WITH SECRETORY
GLANDS)
- ABNORMAL SECRETORY PHASE PATTERN- SOME AREAS
SHOWING EARLY SECRETORY CHANGES AND SOME
AREAS SHOWING MIDSECRETORY CHANGES
- DEFICIENT SECRETORY PHASE ELONGATED,
HYPERCHROMATIC NUCLEI WITH DECREASED
SECRETORY ACTIVITY AND POORLY DEVELOPED STROMA

INFECTIONS
GRANULOMATOUS

INFLAMMATION OF THE
ENDOMETRIUM IS
INFREQUENT,USUALLY
MYCOBACTERIUM
TUBERCULOSIS IS
COMMON
NON NECROTIZING
GRANULOMAS IN LATE
SECRETORY PHASE
GLAND DEVELOPMENT IS
ALTERED LACKING AN
APPROPRIATE
SECRETORY RESPONSE,
PCR CONFIRMS THE
DIAGNOSIS

CLINICAL QUERIES AND

REPORTING
IN

ENDOMETRIAL BIOPSY OR CURRETAGE

FOR INFERTILITY WORKUP, THE
GYNAECOLOGIST SEEKS THE FOLLOWING
INFORMATION
1. HISTOLOGICAL EVIDENCE OF OVULATION
2. HISTOLOGICAL DATE OF THE SECRETORY
PHASE
3. PRESENCE OR ABSENCE OF
ENDOMETRIAL ABNORMALITIES THAT MAY
BE RESPONSIBLE FOR INFERTILITY
( INFLAMMATION AND POLYPS )

DATING THE SECRETORY PHASE IS SOMEWHAT SUBJECTIVE

& NEITHER COMPLETELY EXACT NOR REPRODUCIBLE

RECENTLY MORPHOMETRIC ANALYSIS HAS BEEN ATTEMPTED

TO INCREASE THE ACCURACY OF ENDOMETRIAL
HISTOLOGICAL DATING

MITOTIC RATE IN THE GLAND CELLS

AMOUNT OF LUMINAL SECRETIONS

VOLUME FRACTION OF THE GLAND THAT IS OCCUPIED BY

THE GLAND CELLS

AMOUNT OF PSUEDOSTRATIFICATION OF GLAND CELLS

AMOUNT OF PREDECIDUAL REACTION

SECRETORY PRODUCTS OF ENDOMETRIUM- INTEGRINS HELPS

TO IDENTIFY LUTEAL PHASE DEFECTS.

CAUSES OF UNDATABLE
ENDOMETRIUM
1.HORMONAL
a)
b)
c)
d)
e)

ANOVULATORY
LUTEAL PHASE DEFECT
PERSISTENT CORPUS LUTEUM
EXOGENOUS HORMONES
PREGNANCY

2. ORGANIC LESIONS
a) POLYPS
b) LEIOMYOMA
c) CHRONIC INFLAMMATION
d) HYPERPLASIA
e) CARCINOMA
f) ATROPHY
3. SAMPLING PROBLEMS
g) FRAGMENTATION
h) LACK OF SURFACE EPITHELIUM

FORMAT
1.
2.
3.
4.
5.
6.
7.
8.
9.

NAME :
AGE / SEX :
IP. NO :
CLINICAL DIAGNOSIS :
PROCEDURE :
MENSTRUAL HISTORY :
LMP :
DATE OF PROCEDURE :
HISTORY OF HORMONE INTAKE :