{"paper_id":"e6d0a187-c12e-4367-862e-d67e27618242","body_text":"DOI: https://doi.org/10.53350/pjmhs221617 \nSYSTEMIC REVIEW \n \nP J M H S  Vol. 16, No.01, JAN  2022   7 \nGynaecological Polyps Causing Infertility - a systemic review \n \nSYED JOUN HUSSAIN SHAH 1, SYEDA KHADIJA -TUL-SUGHRA MURRIUM 2, FATIMA NAVEED 3, HAFSA TALAT 4, HAFSA TALAT 5, \nTAIBA SULEMAN5, TEHREEM ZAHRA6, GULL E HINA7 \nThe University of Lahore, 1km Defence Road, Lahore, Pakistan. \nCorrespondence to +92 -3134536559, +92 -3227661994, +92 -335-1543555, dr.syed.joun@gmail.com , fatimanaveed042@gmail.com, \nsyyedakhadija55@gmail.com \n \nABSTRACT \n \nBackground: Polyps of female reproductive tract are found in about 7.8 -50% of women. Endometrial polyps are commonly \nlocated at the fundal or the tubocornual region. They mechanically affect female’s fertility and disturbs the normal cellular  \nfunction due to chronic inflammation. To rule out sub clinical endometrial hyperplasia or cancer, endometrial curettage is often \nrecommended. Cervical polyps may grow during pregnancy or mucorrhoea.  \nAim: To highlight updates to the epidemiology, clinical presentation and diagnostic techniques for gynaecological polyps.  \nStudy design: Systemic review \nMethods: During December 2020 we searched Google scholar, Pub med, Medscape,  Web of Science, Scientific Infor mation \nDatabase and Magiran  research articles from 2010 -2020. The selected articles identified through electronic search were 60 \narticles and 50 were selected for the review. \nResults: Endometrial polyps are the most frequently diagnosed gynaecological polyp, their prevalence ranging from 7.8% to \n50%. They are implicated in about 50% of cases of abnormal uterine bleeding and 35% of patients presenting with infertility. The \ndevelopments of high-resolution 2D and 4D ultrasound, contrast enhanced sonography and hysteroscopy helps in diagnosing \npolyps efficiently. In certain cases, when hysteroscopy cannot be performed sonohysterography and ultrasonography can be \nused for screening. Hysteroscopy is the gold standard technique for the diagnosis of gynaecological polyps and histopathology is \nessential for the ultimate diagnosis and exclusion of malignancy.  \nConclusions: The review of literature suggest that the gynaecological polyps are one of the most common cause of abnormal \nuterine bleeding and have strong association with infertility as they interfere with implantation of an embryo. Polyps can be  \nconfidently diagnosed on ultrasound. Other imaging techniques may provide additional information  about the details of the \nanatomy of female reproductive tract and the polyp itself.  \nKeywords: Endometrial polyp, Cervical polyp, Vaginal/vulvar polyp, Infertility, Ultrasonography, Sonohysterography,. \n \nINTRODUCTION \n \nThe widespread use of ultrasound in gynecological examination \nhas caused  polyps of female genital tract to be  diagnosed more \nfrequently than were previously . For the initial evaluation of all \nuterine pathologies transvaginal ultrasound is considered as a first \nline practical approach whereas the hysteroscopy offers a better \ndiagnostic value generally for all uter ine pathologies and \nspecifically for uterine polyps 1. Endometrial polyp is defined as a \nlocalized hyperplastic overgrowth of endometrial glands and \nstroma. They present with symptoms su ch as menorrhagia, \nintermittent/postmenopausal bleeding and infertility . Endometrial \npolyps are most common gynaecological polyps. They are found in \n25% cases of  AUB and in 35% cases with infertility 2. The \ntransvaginal ultrasound is used as primary approach  for the \ndiagnosis of endometrial polyp s. T he outgrowths of columnar \nepithelium of the cervix  is termed as cervical polyps . They are \nmore frequent in parous or postmenopausal females and about 60 \n- 70% of cervical polyps are asymptomatic [3]. Symptomatic polyps \nare more frequently diagnosed in premenopausal females and may \ncause symptoms such as intermittent bleeding, post-coital bleeding \nor post-menopausal bleeding. The fibro -epithelial polyps are  \nhormone sensitive common lesions which typically occurs in obese \nwomen, its incidence is estimated to be 46% in the general \npopulation4.  \nThese polyps are lo cated in vulvovaginal region and  can \nmanifest in female during reproductive period, pregnancy or  even \nin premenopausal females who are on HRT.  \n \nMATERIAL AND METHODOLOGY \n \nSearch strategy: International {Google scholar, PubMed and Web \nof Science (WOS) } and National { Magiran and Scientific \nInformation Database} databases were searched for related \nobservational studies which were published till 2020 Dec.  \n----------------------------------------------------------------------------------------- \nReceived on 07-07-2021 \nAccepted on 17-12-2021 \nStudy selection : The selected articles picked out  through \nelectronic search comprises the period from 2010 to 2020. The \narticles were reviewed in depth for a more detailed analysi s. \nDatabases reported almost 60 articles and out of them  50 articles \nwere selected for the review. \n \nDISCUSSION \n \nThe aim of this systematic review is to highlight the latest updates \nto the epidemiology, cli nical presentation and various diagnostic \ntechniques for gynaecological polyps providing best guide  to the  \nhealth-workers in their clinical decisions. It also highlights \nprevalence of infertility in patients with gynaecological polyps. We \nhave analyzed almost 60 publications that emphasized on the \ntopics re lated to  female reproductive tract  polyps, their \nepidemiology, clinical presentation , imaging techniques  and \nassociation with infertility . With r ecent advancement in imaging \ntechniques such as 3 -dimensional ultrasound, clinician is able to \ndiagnose polyps and can provide information about their specific \nanatomy and localization. Other imaging modalities also helps the \nclinicians in diagnosing polyps more efficiently. Strong association \nis seen to occurs between polyps and inf ertility as infertility is \nidentified as prevalent among 35% of patients with polyps. \nIt arises from a Greek word “polypus” which means “many \nfeet”. A polyp is defined as a benign polypoidal growth which can \narise from any mucus membrane in the body . Gynaecological \npolyps grow mainly in the uterus and the cervix. They rarely occur \nin the vagina . They are catego rized on the basis of their type, \nlocation, and presence or absence of a stalk5.  \nTypes of gynaecological polyps  \nEndometrial polyps : The most commonly  diagnosed \ngynaecological polyp s are the endometrial polyps . It is an \nabnormal growth containing endometrial glands, stroma and blood \nvessels projecting from the lining of the uterus that may be large or \nsmall enough to occupy  the entire uterine cavity. Endometrial \npolyps can be prevalent during reproductive or postmenopausal \nfemales6. Endometrial polyps are considered hyperplastic growths \nbut are usually benign 2. Gross morphological appearance of an \n\nGynaecological Polyps Causing Infertility \n \n8   P J M H S  Vol. 16, No.01, JAN  2022 \nendometrial polyp is a smooth, cylindrical or spherical  structure \nwhich may be tan to yellow in colour. \nCervical polyps : They are  second most  commonly occuring \npolyps after endometrial polyps and are the most common benign \nlesion of the cervix  which arise within the endocervical canal. The \npapillary proliferations of epithelial tissue around a fibro -vascular \nstromal core which may have glandular or squamous epithelium  \nconstitutes cervical polyp7. Cervical polyp varies in size from 5mm \nto 50 mm and appears as cherry red to purplish red in color. They \nare friable, soft and pedunculated on gross examination which may \nreadily bleed on touch8. \nVaginal/valvar polyps: They are  very rare  hormonal dependent \nbenign disorder. They occur in young to middle-aged women, or in \npregnant females or in females on hormonal replacement therapy9. \nEpidemiological factors   \nEndometrial polyps : They are the most commonly reported  \ngynaecological polyp. Their prevalence ranges from 7.8% to 50% \n[10]. The prevalence of e ndometrial polyp rises with age and \nmenopause. Asymptomatic polyps are mostly discovered during \nroutine physical examination or investigations when women come \nfor infertility evaluation. According to a nother study, they account \nfor 7.8% to 34.9% in patients attending clinics with AUB5.  \nCervical polyps: Cervical polyps are the second most commonly \ndiagnosed polyps next to endometrial polyps. Levy et al. stated \nthat the  endo-cervical polyps occur in about 2-5% of the \npopulation7.  \nVaginal/vulva polyps: Vaginal or vulvar polyps are the rare  \ngynaecological polyps9. \nTopographical classification of polyps: The basic difference \nbetween cervical and endometrial polyps is their localization . The \nfirst step  to categorize gynaecological polyps is on the basis of  \ntheir topography.  \nEndometrial polyps: Endometrial polyps  are located  inside the \nuterine cavity 7. Endometrial polyps  can be  located at any site  \nwithin the endometrial cavity but most frequently  in anterior or \nposterior walls and the fundus. Abnormal uterine bleeding occurs \nin approximately 68% of women and usually more commonly seen \nin women during premenopausal period11. \nCervical polyps: Cervical polyps can be ecto-cervical, present on \nthe outer surface of the cervix or endocervical, present inside the \ncervical canal demarcated by the transformation zone 7. More \ncommon ones are the endocervical polyps and presents in \npremenopausal females. Cervical polyps are mostly asymptomatic \nlesions which are benign in nature.  They are symptomatic mostly \nin postmenopausal women.  Symptomatic cervical polyps \ncommonly manifest as  intermenstrual, post-coital or \npostmenopausal bleeding12.  \nVaginal polyp s: The commonest clinical presentation of fibro -\nepithelial polyp is a painless mass. Other symptoms include pruritis \nand malodorous discharg13. \nStalk formation: Another way to categorize gynaecological polyps \nis on the basis of presence or absence of  a stalk. Pedunculated \npolyps are polyps with narrow elongated stalk and sessile polyps \nare the polyps with no stalk. The more commonly occurring polyps \nare pedunculated polyps. \nHistological type  \nEndometrial polyps: Endometrial polyps are marked by irregular \nglands, fibrotic stroma and thick blood vessels. In rare cases, they \ncan be atrophic, hyperplastic or carcinomatous7.  \nCervical polyps: Cervical polyps are characterized by a central \nfibro-vascular core of stromal cells. These stromal cells are \nsurrounded by a papillary proliferations of cells. These cells may \nbe composed of squamous or glandular epithelium. Squamous \nmetaplasia is commonly seen at the tip of the polyp7.  \nVaginal polyps : They are characterized  as tubulo -squamous in \nnature9.  \nGenetics and predisposition: The most extensively studied \netiological factor is genetic modifications. Other possible etiological \nfactors seen in the published studies are metabolic, drug induced, \nenvironmental factors, age, obesity, hypertension, diabetes \nmellitus, steroid hormone receptors and menopause status 14. Few \nstudies also suggest genetic predisposition of c ervical polyps as \nthey are associated with inflammation7. \nPathogenesis: The exact pathogenesis of gynaecological polyps \nis vague.  \nEndometrial polyps: Pathogenesis of endometrial polyps involves \nglandular, menopause independent AB DNA fragmentation factor \n40, 45 (DFF40), (DFF45) and Bcl -2 o verexpression (Fig. 1) 15. \nMiranda et al. concluded that in polyp of tamoxifen-treated women, \nthe expression of Ki-67 is significantly higher as compared to those \nusing no hormone16.  \nCervical polyps: The pathophysiology is not clearly understood. \nThe possible pathogonesis include chronic inflammation, hormonal \nstimulation or cervical blood vessel congestion17. \nVaginal/vulvar polyps: The pathogenesis of fibro -epithelial polyp \nis uncertain . Several  cases have suggested that a hormonal \ninfluence may be a predisposing condition for developing fibro-\nepithelial polyp13.  \nThe effec t of endometrial polyps on the endometrium: \nIncreased production of glycodelin  associated with  endometrial \npolyps reduces the blood flow to endometrial lining which results in \ndamage of implantation and increases  chances of miscarriage s. \nDue to surface erosion and vascular fragility, AUB is most frequent \nsymptom reported in these cases . Endometrial polyps appear  as \nchronic inflammation or endometrial erosion and is associated with \nvascular dilatation  on hysteroscopy. Ischemic necrosis may \ndevelop at the apex of large polyps18.  \nPolyps in premenopausal women  \nTransvaginal ultrasound : In routine gynaecological \nexaminations, the wide use o f transvaginal ultrasound  has played \na key role to diagnose polyps with  increased accuracy. For the \ndiagnosis of endometrial polyps, baseline imaging technique  used \nis transvaginal ultrasonography . Transvaginal imaging is \nperformed on the 10th d ay of the menstrual cycle to obtain more \naccurate results as the endometrium is thinnest and the \nendometrial poly p will appear mo re prominent . Transvaginal \nimaging is done  by penetrating a trans -vaginal ultrasound probe \nthrough the v agina in order to visualize the uterine cavity. On \nultrasonography, endometrial polyps appear as a hyper -echogenic \nlesion with regular contours 11. According to Babacan et al.,  \ntransvaginal ultrasound has sensitivity and specificity of 19%–96% \nand 53%–100% to diagnose endometrial polyps 1. Fig. 2 \ndemonstrates endometrial polyp on TVS 19. Sonographic \nappearance of cervical polyps is well-circumscribed masses within \nthe endo-cervical canal which may be hypoechoic or echogenic 20. \nFibro-epithelial polyps of vagina appear on ultrasound as \ncircumscribed ovoid homogenous mass21.  \nColour-flow Doppler: Colour Doppler demonstrates a single \nfeeding vessel which is salient feature of endometrial polyps  (Fig. \n3)19. A study carried out by Metello and Jimenez concluded that to \ndiagnose polyps,  power doppler  has increase d sensitivity and \nspecificity around 97% and 95% respectively22.  \nSaline infusion sonography: The addition of intrauterine contrast \nhelps out to outline small polyps which are missed on greyscale \ntransvaginal ultrasound. In year 2018,  Fadl et al reported that  for \nthe diagnosis of endometrial polyps, saline infusion \nsonohysterography provide a better diagnostic accuracy than the \ntransvaginal ultrasound 23. On saline infusion sonography, they \nappear as smooth echogenic masses19.  \nHysteroscopy: Hysteroscopy is a  gold standard  technique for \ndiagnosis and treatment of gynaecological polyps. It is efficient \ndiagnostic technique  in premenopausal  as wells as  in the \npostmenopausal females 11. After excision of a polyp  via \nhysteroscope, endometrial curettage is performed to exclude \nendometrial hyperplasia and cancer via histopathological  \nexamination12. In year 2014, according to a study carried out to \ncompare TVS and hysteroscopy in the diagnosis of uterine \npathologies by Babacan et al. which stated that  hysteroscopic \nevaluation offers better diagnostic value in diagnosing  all uterine \npathologies, particularly the gynaecological polyps1. A comparison \n\nS. J. H. Shah, S. K. T. S. Murrium, F. Naveed et al \n \nP J M H S  Vol. 16, No.01, JAN  2022   9 \nof TVS, saline i nfusion sonohysterography and  hysteroscopy in \ndiagnosis of endometrial pathology in women with AUB was \npublished in 2020 which concluded that in patients presenting with \nAUB, saline infusion sonohysterography was superior to TVS and \nhas a comparable diagnostic accuracy to hysteroscopy in detecting \nuterine pathologies. (Table 3 -7) In countries such as  Africa, for \ndiagnosis of endometrial pathologies saline infusion \nsonohysterography is considered as the first line investigation and \ndiagnostic hysteroscopy is reserved for pa tients with inconclusive \nsaline infusion sonohysterography report24.25. \nHistopathology: It is diagnostic imaging techniq ue for evaluation \nof polyps. \nEndometrial polyps: Endometrial polyps should be confirmed \nmicroscopically by the histopathologist. Under microscopic \nexamination, dense fibrous stromal tissue is visualized as \ncompared to the surrounding endometrium and parallel \narrangement of endometrial gland long axis to the surface \nepithelium is c haracteristic for polyps. The majority of endometria l \npolyps do not respond to hormonal stimul i. They exhibit cystic \nendometrial hyperplasia throughout the menstrual cycle and do not \nshed during menstruation26. (Table 1) \nCervical polyps : On histopathology, in addition to stromal cells  \ncervical polyps exhibit vascular connective tissue covered by the \npapillary proliferation of cells. The  epithelial cells may be \nsquamous, columnar or squamo -columnar. Microscopically, \nhistological patterns are vascular, inflammatory, mucosa, pseudo-\ndecidual, fibrous, a m ixture of cervical and endometrial, and \npseudosarcomatous27 (Table 2). \nVaginal polyps: On histopathologic examination, it  is seen as  a \nfibrocollagenous tissue in the stroma w ith thick blood vessels and \nperivascular infiltrate. This chronic inflammatory infiltrate is \ncovered with stratified squamous epithelium of the vulva28. \nDiagnosis and mana gement of polyps in infertility: \nGyanecological polyps  may cause irritation of the lining of the \nuterus therefore they have strong association with infertility as they \ninterfere with implantation of an embryo . The location of a polyp is \nimportant in addressing fertility issues. \nEndometrial polyps & infertility : Endometrial polyps are \nfrequently seen in sub-fertile women. They are acquired in nature \nand are directly related to dec reased fertility . The prevalence of \nendometrial polyps is up to 32% in  infertile population29. In women \nwith unexplained infertility, the reported frequency of endometrial \npolyps diagnosed by hysteroscopy is to be between 16.5% - 26.5% \n[30]. One hypothesis suggests that mechanical obstruction of the \ntubal ostia caused by an endometrial polyp impairs sperm or the \nembryo from entering into the uterine cavity. The surgical excision \nof endometrial polyps  located at the utero -tubal junction reveals \nbest pregnancy outcomes in case of intrauterine insemination  \ncycles and in ovulation induction18.   \nCervical polyps & infertility: The association  between infertility \nand cervical polyps depends on location where the polyp is \nplaced. Polyps located high up in the cervix can block th e opening \nof the cervix and hinders fertilization31.  \nSpontaneous conception after polypectomy: Studies have \nrevealed increased pregnancy rate in infertile women  is reported \nafter hysteroscopy guided polypectomy , particularly after the \nremoval of tubo-cornual polyps11.  \nIVF and ICSI after polypectomy: Removal of remove endometrial \npolyps is generally prescribed b efore commencement of  in-vitro \nfertilization or intra-cytoplasmic sperm injection treatment. Moon et \nal. proposed that ultrasound guided polypectomy using trans -\ncervical sharp curettage  in women undergoing controlled ovarian \nhyperstimulation or even at the time of ovum pick -up is safe and \ndoes not impact the pregnancy outcome32.  \nStrength and limitations: This systemic review provides an in -\ndepth view of gynaecological polyps that a reader might want \nto study, and the  detail that we have compiled is extremely \nvaluable. However, our study had several  limitations as we \nfocused more on comparing different diagnosing modalities rather \nthan focusing on ultrasonography only as it is first -line diagnostic \nmodality for diagnosing fibroids. \nInterpretations: Endometrial polyps are the most commonly \ndiagnosed gynaecological polyp. They are prevalent in 50% cases \nof AUB and 35% patients with infertility. The developments of high-\nresolution 2 -dimensional and 4-dimensional ultrasound, contrast \nenhanced sonography and hysteroscopy he lps the clinicians in \ndetecting polyps efficiently. Hysteroscopy is the gold standard and \nhistopathology is essential investigation for the ultimate diagnosis \nof polyps and exclusion of malignancy. \n \nCONCLUSION \n \nThe review of literature suggest that the polyps are one most \nfrequent cause of AUB  and infertility. They are efficien tly \ndiagnosed on ultrasounography with d oppler imag ing. Other \nimaging techniques provides addition al information about the \nanatomy of the female reproductive tract and the polyp itself. \nHysteroscopy and histopathological evaluation is considered as a \ngold standard for diagnosis of gynaecological polyps. Furthermore, \ngyanecological polyps have strong assoc iation with infertility as  \nthey interfere with implantation of an embryo by irritating  the lining \nof the uterus. \nCompliance with ethical standards : There is no violation of \nhuman or animal rights.  \nConflict of interest: Authors confirm that this manuscript  has no \nconflict of interest. \nCompeting interests: No competing interests \nFunding sources: This research did not receive any funding \nAuthor contribution: SJH reviewed various articles, data \ncollection, compilation, FN data collection, compilation, \nfigures/tables, analysed data , SK detailed review, HT data \ncollection, TS compilation of data, TZ data analysis and GH \ncompilation of data. \n \nREFERENCES \n \n1. Babacan A, Gun I, Kizilaslan C, et al. Comparison of transvaginal \nultrasonography and hysterosocpy in the diagnosis of uterine \npathologies. Int J Clin Exp Med 2014; 7(3): 764–769. \n2. 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Tanos V, Berry KE, Seikkula J, Abi Raad E, Stavroulis A, Sleiman Z, \nCampo R, Gordts S.  The management of polyps in female \nreproductive organs. Int J Surg. 2017 Jul;43:7-16    \n28. Rexhepi M, Trajkovska E, Besimi F, Rufati N. Giant fibroepithelial \npolyp of vulva: a case report and review of literature. prilozi. 2018 Dec \n1;39(2-3):127-30 \n29. Fatemi HM, Kasius JC, Timmermans A, Van Disseldorp J, Fauser BC, \nDevroey P, Broekmans FJ. Prevalence of unsuspected uterine cavity \nabnormalities diagnosed by office hysteroscopy prior to in vitro \nfertilization. Human reproduction. 2010 Aug 1;25(8):1959-65. \n30. Bosteels J, Weyers S, Puttemans P, Panayotidis C, Van Herendael B, \nGomel V, Mol BW, Mathieu C, D'Hooghe T. The effectiveness of \nhysteroscopy in improving pregnancy rates in subfertile women without \nother gynaecological symptoms: a systematic review. Human \nreproduction update. 2010 Jan 1;16(1):1-1. \n31. Published on February 21, 2017 by SCRC Contributor \n32. Moon JW, Kim CH, Park SY, Kim SH, Chae HD, Kang BM. \nComparison of ultrasound-guided endometrial polypectomy carried out \non the oocyte retrieval day and the first day of ovarian stimulation in \nIVF–ICSI cycles. Reproductive biomedicine online. 2016 Sep \n1;33(3):376-80. \n \n \nTable 1. Histopathological diagnosis of endometrial polyps39                   Table 2. Histopathological diagnosis of cervical polyps40  \n                  \n \n \n \n \n \n \n  \n \n \n \n \n \nTable 3. TVS, SIS, and diagnostic hysteroscopy findings of \npremenopausal and postmenopausal women. [37] \n \n \nTable 4. Sensitivity and specificity of TVS versus hysteroscopy \nin evaluation of endometrial pathology in pre - and \npostmenopausal women [37] \n \n \n\n\nS. J. H. Shah, S. K. T. S. Murrium, F. Naveed et al \n \nP J M H S  Vol. 16, No.01, JAN  2022   11 \n \n \n \nFig. 1 Diagrammatic summary of polyp etiologies38 \n \n \n \n \n \n \n \n   \n \n \n \n \n \n \n  \n \n \nFig. 2 A pedunculated polyp in a 40 -year-old woman with \ninfertility.  \n3-D SIS and colour Doppler demonstrates a solitary, smooth,  \nwell-defined, uniformly echogenic endometrial lesion (P) arising \nfrom the anterior wall with a single feeding vessel (arrow)31 \n \nFig. 3 Power Doppler or colour-flow ultrasound image showing the \nfeeding blood vessel characteristic of an endometrial polyp. Adapted \nfrom Lieng et  al.78 with permission from Professor Marit Lieng, \nDepartment of Gynaecology, RESearch Centre for Obstetrics and \nGynaecology (RESCOG), Oslo University Hospital, Norway34 \n \nTable 5. Sensitivity, specificity PPV and NPV of SIS versus \nhysteroscopy. [37] \n \n \nTable 6. Overall sensitivity, specificity, PPV, NPV, and accuracy \nof TVS versus SIS. [37] \n \n \nTable 7. Comparison of the sensitivity and specificity of SIS and \nTVS in detecting individual endometrial pathologies. [37]","source_license":"CC0","license_restricted":false}