Prevalence; Characteristics and Management of Endometriosis Amongst Infertile Women: A One Year Retrospective Study

Vineet V Mishra¹, Rashmi A Gaddagi², Rohina Aggarwal³, Sumesh Choudhary⁴, Urmila Sharma⁵, Ushma Patel<sup>6

1</sup>Professor and HOD, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.
²Clinical Fellow, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.
³Associate Professor, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.
⁴Assistant Professor, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.
⁵Clinical Fellow, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.
⁶Clinical Fellow, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Centre, Ahmedabad, India.


NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. Vineet V Mishra, Professor & HOD, Department of Obstetrics and Gynaecology, Institute of Kidney Diseases and Research Center (IKDRC and ITS), B.J. Medical College, Civil Hospital, Ahmedabad – 380016, India.
E-mail: vineet.mishra.ikdrc@gmail.com

Endometriosis is a gynaecological enigma since it is difficult to diagnose and treat. It is defined as a chronic and recurrent disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. It is responsible for varied and disabling symptoms and also has adverse effects on reproductive potential. The precise mechanism by which endometriosis causes infertility needs to be evaluated. Endometriosis appears to affect every part of a woman’s reproductive system. It is postulated that women with endometriosis have increased amount of peritoneal fluid associated with increased peritoneal concentrations of prostaglandins, proteases and cytokines including inflammatory cytokines such as IL 1, IL 6 and TNF alpha, and angiogenic cytokines like IL 8 and VEGF [1]. These alterations have an adverse effect on oocyte, sperm, embryo and fallopian tube function [2].

Endometriosis is one of the most common conditions encountered in gynaecological practice. Classic studies have suggested that 25 to 50% of infertile women have endometriosis and 30-50% of women with endometriosis are infertile [3]. The true prevalence of endometriosis is difficult to quantify as very wide ranges have been reported in literature [4,5]. Endometriosis is found in 45% - 82% of women with chronic pelvic pain and in 2.1%-78% of infertile women [6,7]. Nevertheless, its prevalence depends on patient profile and diagnostic tools utilized. However, its prevalence is 6-21 times higher in infertile as opposed to fertile women [8,9].

The role of Ultrasound in the clinical diagnosis of endometriosis is of limited value as it lacks resolution for visualizing adhesions and superficial peritoneal/ovarian implants. Hence laparoscopy is the mainstay in the diagnosis as it provides a visual proof of the minute endometriosis lesions and helps in staging of the disease. In this study, we aim to find out the prevalence of endometriosis amongst infertile women, the demographic & clinical characteristics associated with endometriosis.

This is a retrospective study conducted at the department of Obstetrics and Gynaecology, Institute of Kidney disease and Research centre, Ahmedabad, Gujarat for the period from April 2012 to March 2013.This study aimed to determine the demographic, clinical and laparoscopic characterization of infertile women with endometriosis in addition to type of treatment administered.

Inclusion Criteria: All patients of primary or secondary infertility subjected to diagnostic hystero laparoscopy and chromopertubation test who were diagnosed to have endometriosis were included in the study.

Exclusion Criteria: Women with PID, adhesions due to previous surgeries or infections were excluded.

All patients included in the study were analysed with respect to the following characteristics.

• Clinical Characteristics: Points noted were age, type of infertility, duration of infertility, menstrual cycle – frequency and flow, association of symptoms like dysmenorrhoea, dyspareunia, chronic pelvic pain, urinary symptoms & their correlation to stage of endometriosis.

• Physical Examination: Findings were analysed with respect to presence of abdominal/adnexal masses, mobility of uterus and presence of adnexal tenderness.

• US G FIND ING: Particularly to note endometriomas and probe tenderness.

• Laparoscopic Findings: Endometriotic lesions which were noted varied from dark blue, powder-burn black, red, white, yellow, brown or non-pigmented lesions. The size, depth and location of these lesions were noted to grade the severity of endometriosis. This laparoscopic staging was based on the revised AFS scoring [10] which categorized the finding into 4 stages.

Stage I: (Minimal) involved a few endometrial implants, most often in the cul de sac.

STAGE II : (Mild) comprised of endometrial implants affecting one or both ovaries.

STAGE III : (Moderate) involved moderate levels of endometriosis with implants in several reproductive areas & in one or both ovaries.

Stage IV: (Severe) involved wide spread endometriosis implants through the pelvic area.

All collected data was entered into the SPSS version 20. Categorical data are expressed in frequency or percentage. Chi Square test and Fisher Exact test has been performed to carry out P-value for categorical data. p-value <0.05 shows statistically significant difference.

A total of 372 patients with infertility were subjected to diagnostic hysterolaparoscopy & chromopertubation test during the period from April 2012 to March 2013. Of these, 180 (48.38%) patients had laparoscopic evidence of endometriosis. One hundred thirty five patients (75.0%) had primary infertility and forty five patients (25.0%) had secondary infertility. The mean age of patients was 29± 4.3 years (Range: 19-40 years). Amongst the 180 patients studied, apart from infertility, the commonest complaints were dysmenorrhea (42.22%) followed by menstrual irregularity (17.77%), menorrhagia (12.2%), dyspareunia (9.4%) and chronic pelvic pain (4.41%). However, more than 50% of cases were asymptomatic. There was a statistical significant association between adnexal tenderness and restricted uterine mobility with staging of the disease (p<0.01). Abnormal USG findings were seen in 15% of cases. Presence of cysts/ endometrioma with ground glass appearance was seen in 12.7% of cases. This particular finding was found to be clinically significant as sonograpically detected endometriomas were confirmed laparoscopically. All 11 (100%) cases of stage IV endometriosis in our series had endometriomas in one or both ovaries. Based on Revised AFS score (1985); STAGE 1 endometriosis was seen in 119 patients (66.1%); STAGE II endometriosis in 39 patients (21.66%); STAGE III endometriosis in 11 patients (6.11%); and STAGE IV endometriosis in 11 patients (6.1%). [Table/Fig-1] shows the association of clinical signs and symptoms with stage of disease. [Table/Fig-2] shows the association of laparoscopy & USG findings with stage of disease. In our study, there was a definite correlation of USG and lap evidence of endometriosis with stage of disease. Although most patients of endometriosis in our study were asymptomatic, the presence of dysmenorrhea, dyspareunia and chronic pelvic pain are clinically significant and should always anticipate the presence of subtle endometriosis in these patients. All patients of minimal and mild endometriosis were treated by fulguration /cauterization followed by three doses of GnRH agonist. Moderate and severe endometriosis were treated accordingly depending on laparoscopic findings i.e. adhesiolysis, endometrioma cyst wall excision. This was followed by three doses of leupragon (3.75mg) at an interval of 28 days.

Endometriosis affects 2.5-3.3 percent of women of reproductive age [11] and is diagnosed in 20-68 percent of the women studied for infertility [12]. According to Tsuzi et al., worldwide endometriosis has been found up to 63% [13]. The true incidence of endometriosis is difficult to establish since endoscopy or laparotomy is required for a definitive diagnosis and the disease may still undoubtedly exist in patients who are asymptomatic. It is generally believed, the disease is relatively less common in India, Pakistan, Iran, countries of Middle East and black Africa [14]. Our study demonstrates a very high incidence of 48.33%. Therefore, we feel that the clinical impression of low incidence in Asian and black women may have been due to limited medical and diagnostic facilities available to these women. In our study, every alternative patient had evidence of endometriosis. The commonest sites of endometriosis were the uterosacral ligament (65 cases), Pelvic wall (56cases) Pouch of douglas (40 cases), ovarian fossa (34 cases), and endometrioma (23cases).The other rare sites were uterovesical fold of peritoneum, bowel, round ligament, rectovaginal septum and diaphraghm. One interesting point which we noted was that left side was more involved than the right though it was not found to the statistically significant. The mean age of patients was 29 ± 4.3 years. This is in comparison to other studies which quote low prevalence of endometriosis in either extremes of age & high prevalence in women of reproductive age [15]. Seventy five percent of cases were cases of primary infertility & 25% of case was of secondary infertility. This finding is similar to other descriptive studies [16].

Commonest symptoms encountered in our study were dysmenorrhea (42.2%); irregular cycles (17.7%); menorrhagia (12%); dyspareunia (9.4%) and chronic pelvic pain (4.4%). However, other rare complaints which were noted were urinary complaints like dysurea and difficulty in defaecation in one case of stage 4 endometriosis with frozen pelvis. Statistical significant association of symptoms and signs like dyspareunia, chronic pelvic pain, restricted uterine mobility and adnexal tenderness with staging of disease was noted.However majority of the cases (57.8%) were asymptomatic. We feel that, though none of clinical signs are decisive of endometriosis, positive clinical findings like tenderness on clinical examination, fixation or relatively decreased mobility of uterus or a fixed retroverted uterus or a pelvic mass should always raise the index of suspicion towards endometriosis. The final diagnosis is always by laparoscopy, the gold standard in diagnosis of endometriosis, preferably with histological confirmation [17].

Transvaginal ultrasound lacks adequate resolution for visualizing adhesions and superficial peritoneal/ovarian implants. But when the presence of endometrioma with a typical ground glass appearance is identified, it usually indicates that moderate to severe endomeriosis is present. In our study, there was significant correlation between presence of cysts/endometriomas with ground glass appearance & severity of disease. Out of the 23 diagnosed cases of endometrioma by transvaginal USG, 17 cases were confirmed to have stage III and IV endometriosis on laparoscopy according to R-AFS score (1985).

Majority of the cases of our study had STAGE I endometriosis i.e. 110 cases (66.1%). Most of these patients were asymptomatic and this suggests an early presentation. STAGE II endometriosis was seen in 21% of case and STAGEIII & IV in 6.1% of cases each. All cases of stage IV endometriosis in our study (11 cases) had bilateral endometrioma & frozen pelvis with bowel adhesions. Tubal block was seen in almost 81.81% of case of stage IV endometriosis. Thus there were strong association of laparoscopic findings of endometrioma and blocked tubes. Since our study is a retrospective study, one of the important drawbacks is certain data could not be extrapolated like BMI. BMI & endometriosis by European & Western Studies suggested a positive association [18,19].

All patients in stage I/II received medical management of 3 doses of leupragon (3.75mg) along with fulguration by monopolarcautery of endometriotic spots. Stage III/IV endometriosis underwent adhesiolysis & endometrioma cyst wall excision (based on individual findings) followed by 3 doses of leupragon at 28 days interval. Thus this study highlights the higher prevalence of endometriosis in our population particularly in asymptomatic infertile females. Laparoscopy is the gold standard for diagnosing endometriosis as recommended by ESHRE guidelines [20].

[Table/Fig-1]:

Association of clinical presentations of endometriosis with staging

Clinical signs and symptoms	Stage 1 (of 119)		Stage 2 (of 39)		Stage 3 (of 11)		Stage 4 (of 11)		p-value
	N(%)	OR	N(%)	OR	N(%)	OR	N(%)	OR
Menstrual Irregularity	25 (21.00%)	1.00	4 (10.25%)	0.43	1 (9.09%)	0.38	2 (18.18%)	0.84	0.40 (NS)
Heavy Menstrual flow	12 (10.08%)	1.00	5 (12.82%)	1.31	2 (18.18%)	1.98	3 (27.27%)	3.34	0.36 (NS)
Scant Menstrual flow	6 (5.04%)	1.00	3 (7.69%)	1.57	2 (18.18%)	4.19	1 (9.09%)	1.97	0.39 (NS)
Dysmenorrhea	40 (33.61%)	1.00	23 (58.97%)	2.83	6 (54.54%)	2.37	7 (63.63)	3.45	0.01 *
Dyspareunia	5 (4.20%)	1.00	4 (10.25%)	2.61	3 (27.27%)	8.55	5 (45.45%)	19	<0.01 *
Chronic Pelvic pain	1 (0.84%)	1.00	1 (2.56%)	3.11	1 (9.09%)	11.8	5 (45.45%)	98.33	<0.01 *
Abdominal mass	0 (0.00%)	1.00	0 (0.00%)	N/A	0 (0.00%)	N/A	0 (0.00%)	N/A	-
Tenderness	4 (3.36%)	1.00	4 (10.25%)	3.29	6 (54.54%)	34.5	11 (100%)	N/A	<0.01 *
Adnexal mass	1 (0.84%)	1.00	0 (0.00%)	N/A	2 (18.18%)	26.22	6 (54.54%)	141.6	<0.01 *
Restricted Mobility	1 (0.84%)	1.00	3 (7.69%)	9.83	4 (36.36%)	67.42	10 (90.90%)	1180	<0.01 *

(OR represents Odds Ratios. p <0.05 considered to be statistically significant difference Here, NS represents Non-Significant difference between these groups.)

[Table/Fig-2]:

Association of ultrasonographic & laparoscopic findings with staging of endometriosis

Laparoscopic findings	Stage 1 (of 119)		Stage 2 (of 39)		Stage 3 (of 11)		Stage 4 (of 11)		p-value
	N(%)	OR	N(%)	OR	N(%)	OR	N(%)	OR
Blocked tubes on laparoscopy	16 (13.44%)	1.00	10 (25.64%)	2.22	5 (45.45%)	5.36	9 (81.81%)	28.97	<0.01 *
Endometrioma on Ultrasonography	0 (0.00%)	1.00	7 (17.94%)	N/A	5 (45.45%)	N/A	11 (100%)	N/A	<0.01 *
Endometrioma on laparoscopy	0 (0.00%)	1.00	2 (5.12%)	N/A	3 (27.27%)	N/A	11 (100%)	N/A	<0.01 *

(OR represents Odds Ratios. p <0.05 considered to be statistically significant difference Here, NS represents Non-Significant difference between these groups.)

Endometriosis in infertile females is not uncommon & is increasingly being detected because of greater use of diagnostic modalities like laparoscopy in evaluation of infertility. Though most females are asymptomatic, dysmenorrhoea, chronic pelvic pain, restricted uterine mobility & adnexal tenderness raises the suspicion of endometriosis. Ultrasound evidence of endometrioma has strong correlation to severity of disease. But it is of limited value for diagnosing and determining extent of endometriosis. Laparoscopy remains the gold standard for diagnosing and staging endometriosis.

(OR represents Odds Ratios. p <0.05 considered to be statistically significant difference Here, NS represents Non-Significant difference between these groups.)(OR represents Odds Ratios. p <0.05 considered to be statistically significant difference Here, NS represents Non-Significant difference between these groups.)

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