Histomorphological study of endometrium in primary infertility in Rural setup

Laxmi Agrawal; Kishor Hiwale; Arvind Bhake

doi:10.4103/jdmimsu.jdmimsu_72_18

ORIGINAL ARTICLE

Year : 2021 | Volume : 16 | Issue : 2 | Page : 340-344

Histomorphological study of endometrium in primary infertility in Rural setup

Laxmi Agrawal, Kishor Hiwale, Arvind Bhake
Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (M), Wardha, Maharashtra, India

Date of Submission	31-Dec-2018
Date of Decision	28-Nov-2020
Date of Acceptance	25-Dec-2020
Date of Web Publication	18-Oct-2021

Correspondence Address:
Dr. Laxmi Agrawal
Department of Pathology, DMIMS, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jdmimsu.jdmimsu_72_18

Abstract

Background: In our society, females are blamed for infertility. Females especially in rural places face many problems socially and emotionally. Infertility is an obstacle in the development of couple when it does not take place normally. Infertility is a curse for women, the cause of which should be diagnosed accurately and early. Taking the abovemaintained silent plight of infertile females, this study was conducted based on uterine infertility as a step to increase understanding of pathological causes of primary infertility and serve community on the whole. Aim: This study aims to study histomorphological features of endometrium in primary infertility to know the etiological factors in a rural setup. Objectives: (1) To find various histomorphological patterns of endometrium in primary infertility. (2) To categorize the various etiologic causes under the following heads: (i) Hormonal cause. (ii) Infectious cause. (3) To find the principle cause for primary infertility in the ruler setup. (4) To know the importance of endometrial biopsy/dilatation and curettage (D and C) in primary infertility. Materials and Methods: A total of 99 endometrial sample of primary infertility were received from Department of Obstetrics and Gynecology of confirmed case of primary infertility. The endometrial biopsy or D and C were send in 10% formalin to department of pathology. The samples were processed, stained with hematoxylin and eosin and were studied and categorized into normal proliferative phase, inadequate proliferative phase, anovulatory phase, normal secretory phase, inadequate secretory phase/luteal phase defect (LPD), glandulostromal disparity (GSD), acute endometritis, chronic nonspecific endometritis, and tubercular endometritis. Observation and Results: It was observed that 42.42% patients had normal secretory phase or normal proliferative phase, i.e., it correlates with day of menses. The most common etiological cause for primary infertility was anovulation which was 28.28%. The second most common was LPD/inadequate secretory phase which was 15.15%. Inadequate proliferative phase was 8.08%. GSD was 3.03%. Endometrial hyperplasia was 4.04% among which 3.03% patients had simple hyperplasia without atypia and 1.01% patient had atypical complex hyperplasia. In infections, tubercular endometritis was 2.02% and chronic nonspecific endometritis was 1.01%. In the present study, anovulation was the principle cause of female primary infertility. There were 51.51% patients of primary infertility with hormonal cause and 3.03% patient with infective cause. Conclusion: Anovulation was the principle cause of female primary infertility and LPD was the second common cause of female primary infertility. In infections, tubercular endometritis was common whereas chronic nonspecific endometritis was less. Endometrial biopsy/D and C is a standard tool to know causes of primary infertility, which gives information at cellular level and detects hormonal causes, infective causes for infertility. Thus, by endometrial biopsy/D and C, we come to know the probable cause of female primary infertility, and accordingly, the treatment can be given to patient.

Keywords: Anovulatory cycle, endometrial biopsy and dilatation and curettage, endometritis, infertility, luteal phase defect

How to cite this article:
Agrawal L, Hiwale K, Bhake A. Histomorphological study of endometrium in primary infertility in Rural setup. J Datta Meghe Inst Med Sci Univ 2021;16:340-4

How to cite this URL:
Agrawal L, Hiwale K, Bhake A. Histomorphological study of endometrium in primary infertility in Rural setup. J Datta Meghe Inst Med Sci Univ [serial online] 2021 [cited 2023 Oct 4];16:340-4. Available from: https://journals.lww.com/dmms/pages/default.aspx/text.asp?2021/16/2/340/328477

Introduction

Every women wish to become a mother, failure of which not only causes distress to the women but also to her entire family. The barren marriage is a problem as old in the history of mankind . For continuation and growth of species, reproduction is important and is a basic expectation of life. World Health Organization (WHO) estimates that approximately 8%–10% of couple experience some form of infertility diagnosed as, inadequate proliferative phase, anovulatory, disorders, luteal phase defect (LPD), hyperplasia, abnormal semen parameter, tubal defect, endometriosis, and unexplained infertility.^[1]

WHO estimates that worldwide, 60–80 million couples are currently suffering from infertility.^[2] According to WHO, infertility has been defined as a disease of reproductive system causing failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse.^[3] In India, as per District Level Health Survey-3, female factor causes 8.2% of infertility in married women of age 15–49 years.^[4] According to WHO, one in every four eligible couples in developing countries are affected by infertility by the Demographic and Health Survey conducted from 1990 to 2004.^[2] Endometrial biopsy is one of the oldest and the most important tools in investigation of infertile female. The endometrial biopsy and endometrial histology is considered as the most sensitive indicator of ovarian function. Endometrial biopsy with routine hematoxylin and eosin (H and E) staining is a very important investigation as endometrial biopsy can be practiced in developing countries like India, where complex expensive immunological and hormonal assay procedures are not easily available in rural setup and are also not affordable.^[5] The premenstrual endometrial biopsy is useful in identifying anovulatory cycles, phase defects, and infection, especially tuberculosis and also in confirming ovulation.^[5]

Almost all functional disturbances involved in infertility result in morphological changes in the endometrium since hormone levels fluctuate depending upon various biorhythms. The histological examination of the endometrial biopsy is the most reliable parameter for evaluating the cause of infertility.^[6] This emphasizes the need to study the endometrial biopsy in primary infertility.

Aim

This study aims to study histomorphological features of endometrium in primary infertility to know the etiological factors in a rural setup.

Objectives

To find various histomorphological patterns of endometrium in primary infertility
To categorize the various etiologic causes under the following heads.

Hormonal cause
Infectious cause.

To find the principle cause for primary infertility in the ruler setup
To know the importance of endometrial biopsy/dilatation and curettage (D and C) in primary infertility.

Materials and Methods

Material

This study was conducted at Acharya Vinoba Bhave Rural Hospital (AVBRH), a tertiary care hospital attached to JNMC, Wardha in Central India for a period of 2 years (September 2016 to August 2018). A total of 99 samples of endometrial tissue from confirmed cases of primary infertility attending an infertility clinic in Department of Gynaecology and Obstetrics, AVBRH were examined microscopically. Patients details such as marital history, menstrual history, clinical complaints, period of infertility, obstetric history, and investigation were recorded. The endometrial tissue was obtained by D/C and biopsy procedure for the study by the gynecologist and was send to department of pathology in 10% formalin. Samples were kept for 24 h in 10% formalin; then, tissue processing was done. The section were cut 5 micron in thickness, stained with H and E and examined under microscope.

Inclusion criteria

Females who were unable to conceive after 1 year of regular unprotected intercourse.

Exclusion criteria

Male factors responsible for infertility
Female has gone abortion before.

Methods

Endometrial biopsy analysis

The endometrial biopsy stained with H and E was studied under microscope for morphology of endometrial glands, stroma, and infiltration by inflammatory cells. Dating of endometrium was done according to criteria suggested by Dallenbach-Hellweg.^[7] The reporting was done in light of clinical details. They were divided as follows:

Proliferative phase:

Normal proliferative^[8] phase – Endometrial glands in early, mid, and late proliferative phase and biopsy done in early, mid, and late proliferative phase, respectively
Inadequate proliferative phase – Endometrial glands are comparable to those in early or midproliferative phase were found while the biopsy was done in late proliferative phase or secretory phase
Proliferative (anovulatory) phase – Endometrial glands are comparable to those in late proliferative phase while the biopsy was done in secretory phase
Hyperplasia – Simple hyperplasia and complex hyperplasia with and without atypia.

Secretory phase:^[8]

Normal secretory phase – Dates were matched with the menstrual cycle ± 2 days
Inadequate secretory phase/LPD – Secretory changes lagging behind by 2 or more days of the menstrual cycle
Secretory changes with glandulostromal disparity (GSD) – glandular and stromal changes are discordant

Infective cause:^[8]

Acute endometritis
Chronic nonspecific endometritis
Tubercular endometritis.

Statistical analysis

Statistical analysis was done by–descriptive statistics such as frequency, percentage, mean, and standard deviation (SD) using software SPSS 22.0 version (IBM, Chicago, Illinois, USA).

Observation and Results

During the period of 2 years from September 2016 to August 2018, a total 99 cases of primary infertility were collected. Endometrial samples were received in Department of Pathology JNMC, Sawangi, Wardha for histopathological evaluation with detailed history of patients. The features observed in these endometrial samples (D and C/biopsy) were as follows:

The age of patient presented with primary infertility ranged from 21 to 42 years. Youngest patient was of age 21 years and oldest patient was of age 42 years with mean ± SD of 29.94 ± 4.75 years. 20 patients (20.20%) belong to the age group of 21–25 years, 40 patients (40.40%) were in the age group of 26–30 years, 26 patients (26.26%) were in the age group of 31–35 years, 12 patients (12.12%) are in the age group of 36–40 years, and 1 patient (1.01%) was in the age group of 41–45.

It was observed that duration of infertility varied from 2 to 8 years with mean ± SD of 4.12 ± 1.57. 40 patients (40.40%) presented within 1–3 years of period, 37 (37.37%) patients presented in 4–5 years period, 20 patients (20.20%) presented in 6–7 years, while 2 (2.02%) patients had infertility of 8 years.

Endometrial histomorphological patterns

Endometrial morphological changes were divided into normal proliferative phase, anovulatory, hyperplasia, ovulatory phase, and infective.

In total 99 patients, 3 (3.03%) patients were in normal proliferative phase. Anovulatory was observed in 32 patients, of which 8 (8.08%) patients were in inadequate proliferative phase and 24 (24.24%) patients were in proliferative-anovulatory phase. There were 4 (4.04%) patients of endometrial hyperplasia, of which 3 (3.03%) patients were of simple hyperplasia without atypia and 1 (1.01%) patients of complex hyperplasia with atypia. In ovulatory, 39 (39.39%) patients were in normal secretory phase, 15 (15.15%) patients show inadequate secretory phase/LPD, and 3 (3.03%) patients show GSD. In the present study, 3 (3.03%) patients of infective/endometritis were present, of which 1 (1.01%) patient was of chronic nonspecific endometritis and 2 (2.02%) patients were of tubercular endometritis, as shown in [Table 1].

Table 1: Endometrial histomorphological patterns in patients

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Of total 54 (54.54%) patients of abnormal endometrial finding for primary infertility, 51 patients (94.44%) had hormonal etiology and three patients (5.56%) had infective etiology as shown in [Table 2].

Table 2: Distribution of patients according to etiology

Click here to view

Discussion

Primary infertility is one of the common conditions for which married women visit gynecologist. The endometrial causes of infertility are various like hormonal, infective, neoplastic, and obstructive.

Age of presentation

Age of the female partner has got direct relationship with her reproductive capacity. Fecundability decreases with increasing age. In present study, the age of patient presented with primary infertility ranged from 21 to 42 years with mean ± SD of 29.94 ± 4.75. Maximum 40 (40.40%) patients were in the age group of 26–30 years followed by 26 (26.26%) patients in age group of 31–35 years. The findings of the present study were comparable to the following studies - Lim et al.^[9] - 68.3%, Achalkar^[10] - 81%, and Kafeel et al.^[11] - 46.6%.

Thus, most patients had come within the maximum fertility time.

Duration of infertility

In the present study, duration of infertility ranged from 2 to 8 years with mean ± SD of 4.12 ± 1.57 years. Most of the patients, i.e. 40.40% came within 1–3 years of infertility.

The findings of the present study were similar to the following studies: Girish et al.^[12] - 47.3% and V. Sharma et al.^[13] - 40%.

Thus, maximum patients presented to infertility clinic in time but still large group presented late, and therefore, there is need to spread more awareness in rural setup about female primary infertility.

Histopathology of endometrium

Faithful reflection of ovarian cycle is provided by the endometrial morphology. According to histomorphology, they were divided as proliferative phase, secretory phase, endometritis, and neoplastic. In the present study, proliferative phase was seen in 39 (39.39%) patients, secretory phase in 57 (57.57%) patients, and endometritis in 3 (3.03%) patients.

Proliferative phase

It was further divided as–

Normal proliferative phase – In the present study, 3 (3.03%) patients had normal proliferative phase. In the study by Nandedkar et al.,^[8] 2015, it was 39.72%. This difference can be due to the difference in day of biopsy.
Inadequate proliferative phase – In the present study, 8 (8.08%) patients had inadequate proliferative phase while it was 5.79% in study by Nandedkar et al.,^[8] 2015. Thus, results were similar and therefore inadequate proliferative phase should be considered as a cause of infertility and biopsy can be advised in proliferative phase to detect inadequate proliferative phase defect in case where biopsy in secretory phase is normal.
Proliferative phase (anovulatory) – In the present study, 28 (28.28%) patients had anovulatory phase which was the most common cause of infertility in the present study. Similar results were seen in study by Girish and Manjunath^[5] - 27.8%, V. Sharma et al.^[13] - 29.73%, Kaur et al.^[14] - 33%, and Murmu et al.^[15] - 21.92%.

Endometrial hyperplasia – A total of 4 (4.04%) patients of hyperplasia were found in the present study in which 3 (3.03%) patients showed simple hyperplasia without atypia and 1 (1.01%) patient was of complex hyperplasia with atypia. The results were quite similar with the study by Nandedkar et al.,^[8] 2015, who found 0.91% patient of hyperplasia in which maximum patients were of simple hyperplasia without atypia and very less 0.096% patient of complex hyperplasia in primary infertility.

Nisa,^[16] 1983, found 3% of patients of endometrial hyperplasia which was similar with the present study. Similarly, the results of the present study were comparable with Sahmay et al.,^[17] 1995-4.68% of hyperplasia patients, Girish and Manjunath^[5] - 4% of simple hyperplasia patient, Murmu et al.^[15] - 2.74% patients of simple cystic hyperplasia, and Lim et al.^[9] - 2.9% patients of hyperplasia.

Secretory phase – it was further divided as

Normal secretory phase – In the present study, 39.39% patients were in normal secretory phase. Maximum number of patients had normal finding of endometrium on histomorphology.

et al

^[8]

et al

^[18]

et al

^[15]

Inadequate secretory phase/LPD – In the present study, 15.15% patients had inadequate secretory phase/LPD which was the second most common cause of infertility in the present study. The results were comparable with study by Sahmay et al.^[17] - 28.3%, Nandedkar et al.^[8] - 11.07%, V. Sharma et al.^[13] - 20%, Murmu et al.^[15] - 8.22%, and Achalkar^[10] - 20%.

GSD – In the present study, GSD was present in 3.03% of patient which was similar with study by Nandedkar et al.,^[8] 2015, - 4.75%.

Infections/endometritis

Acute endometritis – There was no case of acute endometritis in the present study which was similar to the study by Achalkar,^[10] 2018, Nandedkar et al.,^[8] 2015, Nasir et al.,^[18] 2016, and Gupta et al.,^[19] 2013.
Chronic nonspecific endometritis – In the present study, 1.01% patients had chronic nonspecific endometritis which was similar to the study by Ahmed et al.,^[2] 2018-1.44% of patients, Girish and Manjunath,^[5] 2011-2.7% of patients, Kasius et al.,^[20] 2011-2.8% of patients.
Tubercular endometritis – In the present study, 2.02% patient had tubercular endometritis.

The similar results were seen in study by Nisa,^[16] - 2.6%, Lim et al.,^[9] - 1.9%, V. Sharma et al.,^{[ 13]} - 2%, Murmu et al.,^[15] - 1.37%

Distribution according to etiology

Of total 54 patients of abnormal endometrial pattern on histopathology of patients of primary infertility, maximum 51 patients (94.44%) had hormonal cause for primary infertility whereas 3 patients (5.56%) had infective cause for primary infertility.

Conclusion

The present study concluded that most common age group of presentation was 25–30 years of age. Maximum patients presented within 1–3 years of infertility. Various abnormal patterns of endometrium in primary infertility are inadequate proliferative phase, anovulatory cycle, inadequate secretory phase/LPD, GSD, chronic nonspecific endometritis, and tubercular endometritis. Hormonal cause was the most common etiological cause for female primary infertility. Hormonal causes for primary infertility were anovulatory cycle, followed by LPD, inadequate proliferative phase defect, and GSD. In infective cause, most common was tubercular endometritis followed by chronic nonspecific endometritis. Anovulation was the principle cause for female primary infertility. Endometrial biopsy is most valuable, reliable, informative investigation to detect cause of infertility. Endometrial biopsy is one of the most important tools in workup of primary infertile female which not only detects hormonal dysfunction but also intrinsic factors for infertility by which cause can be detected and treatment can be given to infertile female. It provides simple and faithful reflection of ovarian cycle and also provides information about local factors in endometrium at cellular level.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Afroz N, Singh M, Verma M, Bansal V. Female infertility: Role of vaginal hormonal cytology, endometrial biopsy and endocrinological evaluation. J Indian Med Assoc 2006;104:124-6, 128.
2.	Ahmed M, Afroze N, Sabiha M. Histopathological study of endometrium in infertility: Experience in a tertiary level hospital. Birdem Med J 2018;8:132.
3.	Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 2009;92:1520-4.
4.	Available from: http://www.who.int/reproductivehealth/topics/infertility/DHS-CR9.pdf. [Last accessed on 2018 Jul 27].
5.	Girish CJ, Manjunath ML. Morphological patterns of endometrium in infertile women-a prospective study. Int J Appl Biol Pharm Technol 2011;2:512-20.
6.	Dallenbach-Hellweg G. The endometrium of infertility. A review. Pathol Res Pract 1984;178:527-37.
7.	Dallenbach-Hellweg G. Histopathology of the Endometrium. 4^th ed.. London, Paris, Tokyo: Springer-Verlag; 1987. p. 57–92.
8.	Nandedkar SS, Patidar E, Gada DB, Malukani K, Munjal K, Varma A. Histomorphological patterns of endometrium in infertility. J Obstet Gynaecol India 2015;65:328-34.
9.	Lim SC, Choi JB, Kee KH, Jeon HJ, Suh CH. Histopathologic study od the endometrium in primary infertility. Korean J Pathol 1991;25:196-205.
10.	Achalkar GV. Histopathological study of endometrium in infertility. J Evol Med Dent Sci 2018;7:2870-3.
11.	Kafeel S, Mushtaq H, Alam S. Endometrial histological findings in infertile women. J Islamabad Med Dent Coll 2012;2:61-4.
12.	Girish CJ, Kotur NS, Nagarajappa AH, Manjunath ML. A correlative study of endometrial glycogen content and other contributory factors on female infertility. Int J Biomed Adv Res 2012;3:30-5.
13.	Sharma V, Saxena V. Histopathological study c. Clin Exp Pathol 2016;6:272. Available from: https://www.omicsonline.org/open-access/histopathological study-of- endometrium in cases-of-infertility-2161-0681-1000272.php?aid=72355. [Last accessed on 2018 Aug 09].
14.	Kaur P, Kaur A, Suri AK, Sidhu H. A two year histopathological study of endometrial biopsies in a teaching hospital in Northern India. Indian J Pathol Oncol 2016;3:508.
15.	Murmu S, Baitha B, Singh US. A histopathological study of endometrium in infertility. IOSR J Dent Med Sci 2017;16:56-60.
16.	Nisa Z. The value of endometrial biopsy in infertility. J Pak Med Assoc 1983;33:304-5.
17.	Sahmay S, Oral E, Saridogan E, Senturk L, Atasu T. Endometrial biopsy findings in infertility: Analysis of 12,949 cases. Int J Fertil Menopausal Stud 1995;40:316-21.
18.	Nasir S, Khan MM, AhmadS, Ziaullah S, Alam S. Morphological spectrum of endometrial biopsies in infertile women. Gomal J Med Sci 2016;14:151-5.
19.	Gupta A, Mathur SK, Gupta A. Correlation of histological dating and glycogen content by histochemical stain during various phases of menstrual cycle in primary infertility. Open J Pathol 2013;3:65-8.
20.	Kasius JC, Fatemi HM, Bourgain C, Sie-Go DM, Eijkemans RJ, Fauser BC, et al. The impact of chronic endometritis on reproductive outcome. Fertil Steril 2011;96:1451-6.