{"paper_id":"636b84bf-aaa3-4b31-b3a1-ec31698be5d4","body_text":"21\nCopyright © Jeju National University Institute for Medical Science\nJournal of Medicine and Life Science Vol. 21, No. 2, 21-30, May 2024\nhttps://doi.org/10.22730/jmls.2024.21.2.21\nHysteroscopic evaluation of endometrial changes and fallopian \ntubal functions in women using progestin-only contraceptives\nAtef Darwish, Ibrahim Mohammad, Samuel Gendy, Dina Darwish, Mohammad Ramdan\nDepartment of Obstetrics & Gynecology, Woman’s Health University Hospital, Assiut University Faculty of Medicine, Assiut, \nEgypt\nAbstract The purpose of this prospective study was to investigate whether \noffice hysteroscopy (OH) can be used to assess the mechanisms of action of \nprogestogen-only contraceptives (POCs), diagnose possible local causes of \nabnormal uterine bleeding (AUB), and support the treatment plan of symptomatic \npatients using POCs compared with those who do not use hormones. The study \nincluded 140 women who were divided into two groups. Group A consisted of 70 \nwomen who used POCs, whereas group B consisted of 70 women who did not use \nhormones. They were successively examined using transvaginal ultrasonography \n(TVS), OH, and endometrial sampling. The TVS results were consistent with those \nof OH and histopathology. The changes in endometrial thickness and vasculature, \nas well as fallopian tube (FT) functions, were significantly more pronounced in POC \nusers than in non-POC users. There was a significant reduction in the peristalsis of \nthe proximal part of the FT, as well as a reduction in the bubble flow test in group A \ncompared with group B. In addition, the combination of peristalsis and the bubble \nflow test (Darwishscope test) was significantly lower in group A. It was concluded \nthat using OH as a simple diagnostic tool in women with POCs would contribute \nto a better understanding of the mechanisms of endometrial and FT effects and \nexplain some local endometrial causes of AUB. This ensures that the combination \nof TVS and OH would limit routine endometrial sampling in POCs users.\nKey words:  Endometrium, Fallopian tubes, Hysteroscopy, Contraception, \nProgestins, Ultrasonography\nReceived : November 16, 2023\nRevised  : January 16, 2024\nAccepted : February 9, 2024\nCorrespondence to \nAtef Darwish\nDepartment of Obstetrics & Gynecology, \nWoman’s Health University Hospital, \nAssiut University Faculty of Medicine, \nBesery Way, Al Walideyah Al Qebleyah, \nAsyut 2, Assiut 71111, Egypt\nTel: 20-0201001572723\nFax: 20-02-088-2368377\nE-mail: atef_darwish@yahoo.com\nOriginal Article\nINTRODUCTION\nAn increasing number of progestogen-only contraceptives \n(POCs) are being used worldwide because they have no \nestrogen-related side effects or complications, do not inter-  \nfere with breastfeeding, and interest in long-acting reve-  \nrsible contraceptive methods (LARC) is increasing. The \npossible mechanisms of the contraceptive action of POCs \ninclude inhibition of ovulation at varying percentages, \nalteration of the biophysical properties of cervical mucus, \nreduction of fallopian tube (FT) ciliary motility and tubal \ncontractile muscle strength, and/or alteration of endometrial \nreceptivity.\n1\n However, the incidence of unwanted and distres- \nsing forms of abnormal uterine bleeding (AUB) was sign-  \nJournal of Medicine \nand Life Science\neISSN: 2671-4922\n\n\nVol. 21, No. 2, May 2024\n22\nhttps://medsci.jejunu.ac.kr/\nJournal  of  Medicine  and  Life  Science\nificantly higher with POCs than with other methods.\n2-7\n There \nis a need for a better understanding of the mechanisms  \nof AUB in women using POCs,\n8\n and thus for individualized \ntreatment rather than the current empirical lines of therapy.\n9\nOffice hysteroscopy (OH) has long been used to examine \nthe uterine cavity in many gynecological conditions such  \nas AUB,\n10\n unexplained infertility, and recurrent pregnancy \nloss.\n11,12\n In recent years, we have extensively studied the \nproximal part of the FT using a bubble flow test and phys -\niological peristalsis via OH.\n12\n In addition, the combination \nof the bubble flow test and peristalsis (Darwishscope test) \nproved to be better than either test alone for assessing the \nfunction of the proximal part of the FT.\n13\n This study aimed \nto assess whether OH can be used to evaluate the mecha -\nnisms of action of POCs, diagnose possible local causes of \nAUB, and support in developing a treatment plan for pa -\ntients experiencing symptoms who use POCs compared to \nthose who do not use hormones.\nMETHODS\nThis prospective cross-sectional study was conducted \nbetween August 2021 and July 2023 at the OH unit of the \nWomen’s Health University Hospital of Assiut University, \nin women of childbearing age who had undergone OH for \nvarious indications. This study was approved by the eth -\nics committee of the Faculty of Medicine (No. 17101330) \nand registered on ClinicalTrials.gov (NCT04368104). The \nsample size was calculated using G*Power 3.1.3 software \n(Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Ger -\nmany) and amounted to 140 cases, which were divided into \ntwo groups according to the use of POCs. Group A included \n70 patients who used any method of POCs and complained \nof AUB with or without abnormal transvaginal ultrasonog -\nraphy (TVS). Group B comprised women with infertility \nwho underwent OH during the same period but did not use \nhormones or contraceptives. After preoperative counseling, \nall patients agreed to provide written consent. A complete \nmedical history was obtained from all patients, including a \nhistory of contraceptive use (method, duration, regularity \nof use, side effects, complications, and any interruptions), \na therapeutic history, and a thorough physical examination. \nClinically, biochemically, or sonographically diagnosed pre- \ngnancies, recent stroke or ischemic heart disease, heavy \nvaginal bleeding, active pelvic inflammatory disease, coag-\nulopathies, and severe comorbidities, such as severe hyper-\ntension and severe cardiac, neurological, or breast disease, \nwere excluded from this study. Women using any form of \ncontraception or hormones were excluded from group B. \nThe vulva, vagina, and thighs were disinfected with a 10% \npovidone-iodine solution. Subsequently, sterile drapes were \napplied. OH was performed with a rigid 2.6 mm 30° scope \nwith a 3.2 mm outer sheath (Karl Storz, Tuttlingen, Germa-\nny). Initially, a vaginoscopic approach was attempted in all \ncases; however, if difficulties were encountered, the anterior \nlip of the cervix was grasped using a multitoothed volsel -\nlum. The uterus was then distended with normal saline at a \npressure of 60-80 mmHg, which was generated by a pneu -\nmatic sphygmomanometer cuff wrapped around a 500 mL \n0.9% saline infusion bottle. The endoscope, connected to a \n250 W Xenon light source, was carefully inserted through \nthe cervical canal and internal os. To perform a perfect \nhysteroscopic assessment of the endometrial cavity, the \nfollowing steps were followed: a clear panoramic view of \nthe uterine cavity was achieved by placing the hysteroscope \ninto the cervical canal and waiting for a while to achieve \nhomogeneous dilation and drainage of blood clots from the \ncervix. The uterine cavity should be examined systematical-\nly, starting with the anterior and posterior fundus and lateral \nwalls. The examination is considered complete when both \ntubal ostia have been reached, and any gross pathology, \nsuch as septum, adhesions, polyp(s), myoma, or any prolif -\neration, has been described. Hysteroscopic assessment of \nthe endometrial thickness began with a revision of the TVS \nreport. During TVS, an endometrium (EM) of 8-11 mm was \nconsidered normal. For OH, the EM was considered normal \nif it appeared to be of normal thickness, with moderately \ndeveloped glandular orifices, and evenly distributed blood \nvessels in a healthy endometrium. For TVS, a thin EM was \nassumed if it was ≤7 mm. In OH, a thin EM was assumed \n\n Office hysteroscopy in progestin-only contraception\n23\nhttps://medsci.jejunu.ac.kr/\nAtef Darwish, Ibrahim Mohammad, Samuel Gendy, Dina Darwish, Mohammad Ramdan \nwhen narrow glandular openings and thin, poorly distrib -\nuted blood vessels were observed in the fragile endometri -\num.\n14\n In the TVS, a thick EM was assumed when it meas -\nured 12-16 mm (excluding the secretory phase). A thick EM \nwas identified in the OH as diffusely increased thickness \nwith prominent glandular orifices. In TVS, endometrial hy-\nperplasia is assumed when the EM appears as an echogenic \ndiffuse smooth thickening >10 mm. Hysteroscopically, it is \nrecognized as local or diffuse endometrial thickening with \na papillary or polypoid appearance, abnormal vascular pat -\nterns, glandular cysts, and glandular outlets with abnormal \narchitectural features.\n15\nIn addition to the subjective assessment of endometrial \nthickness, a simple hysteroscopic endometrial thickness test \nwas performed. The telescope was advanced until the fun -\ndus was reached and then extracted along the posterior wall \nup to the cervix with gentle pressure. If a significant furrow \n(half the circumference of the hysteroscopic sheath) formed \nalong the pathway, the EM was considered thick. If there \nwas no furrows were observed, the EM was mostly thin. If \na shallow furrow (one-quarter of the circumference of the \nhysteroscopic sheath) is formed, it is mostly a normal EM. \nThe endometrial vasculature appeared normal, congested, \nwith petechiae, ecchymosis, and abnormal or suspicious \nvascular patterns. The endometrial color was pale, pink, \nreddish, or dark red, as previously described.\n10\n All cases re-\nported bleeding upon touching.\nThe next step in all cases was to assess FT function. \nPrerequisites for successful access to the FT via hysteroscopy \ninclude the utilization of a 300 mm telescope and skillful \nuse of its rotation to reach both cornua (tilting it to the \nright to see the left side and vice versa). The fundamental \nanatomic triad (Darwish hysteroscopic triad) was observed \n(Darwish triad, DT).\n16\n This is the conical part of the FT (Fig. \n1A). Its base is a fine cornual circle (ostium) representing \nthe end of the endometrial cavity. The ostium is followed by \na shallow conical groove, which is the converging wall of \nthe first millimeter of the intramural part of the FT. Finally, \nFigure 1. (A) Darwish hysteroscopic triad. (B) Bubble flow test (a bubble is seen at the ostium). (C) Congested thin endometrium with evident \ncapillaries. (D) Congested thin endometrium in the form of dilated, tortuous, and worm-like capillaries.\nB\nD\nA\nC\n\nVol. 21, No. 2, May 2024\n24\nhttps://medsci.jejunu.ac.kr/\nJournal  of  Medicine  and  Life  Science\na distal pinhole dark spot (the narrowest part of the FT) rep-\nresents the summit of the cone. Considering DT is essential \nin evaluating tubal patency and physiology during hys -\nteroscopy. If the DT was clearly accessible, a comment was \nprovided regarding its shape. If there were osteal lesions, \nsuch as tiny polyps or fine adhesions, which may hinder the \nproper evaluation of tubal anatomy and physiology, the hys-\nteroscopist would report them. The passage of air bubbles \nin the irrigating fluid towards the DT has been reported. If \nthere was no air bubbles were observed, the hysteroscopist \ninjected 2 mL of air into the rubber end of the sterile in -\nfusion set. The results of the hysteroscopic bubble suction \ntest were considered positive if air bubbles passed through \nthe DT within 1 minute (Fig. 1B). During this period, nei -\nther air injection nor increased pressure was applied. If no \npassage of gas bubbles occurred, the examiner waited for 1 \nminute to exclude tubal spasms. If there were no passage of \nbubbles through the DT and their accumulation at the cor -\nnual end, the test was considered negative. Simultaneously, \ncareful visualization of any changes in the shape of the os -\ntium and the intramural part of the FT, particularly during \nthe passage of air bubbles, was recorded in all cases. Tubal \nperistalsis is defined as the rhythmic opening and closing \nof the ostium and intramural fallopian tube under constant \nintrauterine pressure, that is, periodic changes in the DT in \nthe form of widening followed by collapse on meticulous \nobservation. If the ostium and intramural part of the tube \nwere opened, followed by the collapse and non-visualiza -\ntion of the dark pinhole spot of the DT for a while, positive \nperistalsis was reported. The same procedure was repeated \non the contralateral side. At the end of OH, Novak’s curette \nbiopsies of the most suspicious areas of EM were obtained \nunder hysteroscopic guidance and sent for histopathological \nexamination.\nThe SPSS version 24 (IBM, Armonk, NY, USA) was used \nto analyze the data. Quantitative data were expressed as \nmean±standard deviation. Qualitative data were expressed \nas frequencies and percentages. The independent-sample \nTable 1. Sociodemographic data of studied patients\nCharacteristic Study group (n=70) Control group (n=70) Test P-value\nAge (years) 29.81±4.96 31.29±5.53 1.67\n†\n0.10\nParity 3 (1-5) 2 (0-3) 845\n‡\n0.001*\nResidence \nRural 39 (55.7) 42 (60.0)\nUrban 31 (44.3) 28 (40.0) 0.264\n§\n0.608\nEducation \nIlliterate 39 (55.7) 35 (50.0)\nPrimary school 18 (25.7) 20 (28.6)\nSecondary school 10 (14.3) 13 (18.6)\nHigh level 3 (4.3) 2 (2.9) 0.913\n§\n0.822\nOccupation \nHousewife 62 (88.6) 65 (92.9) 0.763\n§\n0.382\nEmployee 8 (11.4) 5 (7.1)\nInfertility\nYes 0 (0.0) 62 (88.0) 107.72\n§\n<0.001*\nNo 70 (100.0) 8 (12.0)\nValues are presented as frequency (%), mean±standard mediation, or median (range). \n*P-value was significant if <0.05.\n†\nIndependent t-test.\n‡\nMann Whitney U test.\n§\nChi square test. \n\n Office hysteroscopy in progestin-only contraception\n25\nhttps://medsci.jejunu.ac.kr/\nAtef Darwish, Ibrahim Mohammad, Samuel Gendy, Dina Darwish, Mohammad Ramdan \nt-test and Mann-Whitney U test were used to compare the \nmeans of normally and abnormally distributed data, respec-\ntively. The chi-squared test was used to compare nonpar -\nametric data. Probability ( P-value) <0.05 was considered \nsignificant, <0.001 was considered highly significant, and \n>0.05 was considered non-significant. \nRESULTS\nThis prospective study included 140 patients who under -\nwent OH and were divided into two groups. Group A used \nPOCs, whereas group B included infertile women who did \nnot use any hormones. There were no statistically signif -\nicant differences between the groups regarding sociode -\nmographics, apart from parity and infertility, as shown in \nTable 1. Group A was using POCs in the form of traditional \nprogesterone-only pills (POP) containing levonorgestrel \n(LNG) 0.03 mg (Microlut; Bayer, Leverkusen, Germany) \nin 21 cases, desogestrel-containing POP 75 g (Cerazette; \nMSD, Rahway, NJ, USA) in 11 cases, etonogestrel implants \n68 mg (Implanon; MSD) in 16 cases, medroxyprogesterone \nacetate (MPA) 150 mg (Depo-Provera; Pfizer, New York, \nNY, USA) in 20 cases, and LNG intrauterine system (IUS) \n52 mg (Mirena; Schering AG, Berlin, Germany) in two cas-\nes. The mean duration of exposure to POCs was 6.56±3.05 \nmonths, with a range of 3 to 18 months. Table 2 shows the \nTable 2. Indications of office hysteroscopy among studied patients\nIndication of office hysteroscopy Study group (POCs) (n=70) Control group (infertility) (n=70) Chi-square test P-value*\nBreakthrough bleeding 34 (48.6) 0 (0.0) 118 <0.001\nMenorrhagia 18 (25.7) 8 (11.4)\nMetrorrhagia 11 (15.7) 0 (0.0)\nSuspected IU lesion by TVS 7 (10.0) 0 (0.0)\nUnexplained infertility 0 (0.0) 31 (44.3)\nPre-ICSI 0 (0.0) 31 (44.3)\nValues are presented as frequency (%).\nPOC: progestogen-only contraceptive, IU: intrauterine, TVS: transvaginal ultrasonography, ICSI: intracytoplasmic sperm injection.\n*\nP-value was significant if <0.05.\nTable 3. Indications of office hysteroscopy among studied patients\nCharacteristic\nStudy group A\nControl group \nB (n=75) Chi-square P-value*Total  \n(n=70)\nMPA  \n(n=20)\nMicrolut  \n(n=21)\nImplanon \n(n=16)\nCerazette \n(n=11)\nMirena \n (n=2)\nEndometrial thickness\nNormal 36 (51.4) 5 (25.0) 14 (66.7) 6 (37.5) 9 (81.8) 2 (100.0) 60 (85.7) 19 <0.001\nThin 27 (38.3) 12 (60.0) 7 (33.3) 7 (33.3) 1 (9.1) 0 (0.0) 1 (1.4) 30 <0.001\nPolyp 3 (4.3) 2 (10.0) 0 (0.0) 0 (0.0) 1 (9.1) 0 (0.0) 7 (10.0) 1.72 NS\nSubseptate uterus 3 (4.3) 0 (0.0) 0 (0.0) 3 (18.7) 0 (0.0) 0 (0.0) 1 (1.4) 1.03 NS\nEndometrial hyperplasia 1 (1.4) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.4) - NS\nEndometrial vasculature\nNormal 45 (64.3) 4 (20.0) 17 (81.0) 12 (75.0) 10 (90.9) 2 (100.0) 61 (87.1) 9.95 0.002\nPale 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (7.1) 22.62 <0.001\nCongested 25 (34.7) 16 (80.0) 4 (19.0) 4 (25.0) 1 (9.1) 0 (0.0) 4 (5.7) 19 <0.001\nValues are presented as frequency (%).\nMPA: medroxyprogesterone acetate, NS: no significance.\n*\nP-value was significant if <0.05.\n\nVol. 21, No. 2, May 2024\n26\nhttps://medsci.jejunu.ac.kr/\nJournal  of  Medicine  and  Life  Science\nindications for OH in both groups. The only significant \ndifference between the two groups was the documentation \nof viscid cervical mucus in 26 cases (37.1%) in group A out \nof 32 cases using POP compared to zero cases in group B \n(\nP<0.001). Regarding the endometrial cavity, most cases in \nboth groups showed normal appearance, thickness, color, \nand vasculature. However, in group A, thin EM and ab -\nnormal vasculature were significantly higher than those in \ngroup B (27 [38.3%] vs. 1 [1.4%] and 25 [34.7%] vs. 4 [5.7%], \nrespectively), as shown in Table 3. Preoperative TVS was \nconsistent with OH comments on endometrial thickness \nin most cases in both groups. Fig. 1C shows a congested \nEM with obvious capillaries, while Fig. 1D shows dilated, \ntortuous, and worm-like capillaries prone to easy bleeding \nupon touch in the cases of AUB in group A. Access to DT \nto assess FT was successful in most cases in both groups. \nHowever, due to excessive bleeding, it was unsuccessful in \na few patients (Table 4). FT function assessment revealed \na significant reduction in peristalsis in the proximal part of \nthe FT, in addition to a decreased bubble flow test in group \nA than in group B. Moreover, the combination of peristalsis \nand bubble flow tests (Darwishscope test) was significantly \nlower in the POCs group, especially for the right FT. Only \n21 (30%) and 20 patients (29%) in both groups were satisfied \nwith OH, respectively, but the rest were dissatisfied because \nof painful endometrial sampling using a Likert scale. The \nhistopathological diagnosis was consistent with the hystero-\nscopic diagnosis in both groups. \nDISCUSSION\nHormonal contraceptive use, including POCs, has incre-  \nased worldwide, accounting for almost 50% of contraceptive \nmethods.\n17\n It is well-documented that POCs may induce \na progressive reduction of endometrial thickness over \nthe course of treatment,\n18,19\n as supported by the findings \nof this study of OH subjective assessment. A simple and \neasy practical technique was used to assess endometrial \nTable 4. Hysteroscopic evaluation of the Fallopian tubes in both groups\nCharacteristic Study group (n=70) Control group (n=70) Chi-square P-value*\nDarwish hysteroscopic triad (FT) access \nRight tube 65 (92.8) 64 (91.4) 1.14 NS\nLeft tube 65 (92.8) 66 (94.2) 1.90 NS\nPositive bubble flow test within 1 minute\nRight tube 28 (40.0) 45 (64.3) 8.27 0.004\nLeft tube 30 (42.9) 47 (67.1) 8.34 0.004\nPositive bubble flow test within 2 minutes\nRight tube 29 (41.4) 48 (68.6) 10.40 0.001\nLeft tube 31 (44.3) 49 (70.0) 9.45 0.002\nTotal positive test \nRight tube 29 (41.4) 48 (68.6) 10.40 0.001\nLeft tube 31 (44.3) 49 (70.0) 9.45 0.002\nPositive tubal peristalsis \nRight tube 16 (22.8) 35 (50.0) 11.10 <0.001\nLeft tube 21 (30.0) 33 (47.1) 3.65 0.056\nDarwishscope test (combined bubble and peristalsis)\nRight tube 15 (21.4) 33 (47.1) 10.30 0.001\nLeft tube 17 (21.2) 29 (41.4) 3.92 0.048\nValues are presented as frequency (%).\nFT: fallopian tube, NS: no significance.\n*\nP-value was significant if <0.05.\n\n Office hysteroscopy in progestin-only contraception\n27\nhttps://medsci.jejunu.ac.kr/\nAtef Darwish, Ibrahim Mohammad, Samuel Gendy, Dina Darwish, Mohammad Ramdan \nthickness by applying gentle pressure along the entire \nposterior wall. These findings were consistent with the \npreoperative TVS and histopathological results in all cases. \nAdditional advantages of OH over TVS include being the \ngold standard diagnostic tool for observing tiny lesions \nor abnormal vasculature and assessing FT function. OH \nprovides a visual assessment of the EM vasculature. It \nwas able to diagnose a normal endometrial vasculature \npattern in 45 patients (64.3%) and a congested pattern in \n25 POCs users (34.7%). Endometrial findings have been  \npreviously reported in greater detail, particularly in users  \nof norplant implants,\n20\n but were solely based on endometrial \nsampling. A hysteroscopic diagnosis of a free endometrial \ncavity or any intrauterine lesion (supported by normal TVS) \nminimizes the burden on the pathologist by eliminating \nunnecessary samplings.\n21\n Moreover, it also alleviated \ninvasive endometrial sampling pain, which was experienced \nby 49 (70%) and 50 patients (71%) in groups A and B, \nrespectively. Furthermore, this also alleviated the anxiety \nand stress of waiting several days for biopsy results. In \naddition to the fact that these women are usually young \nand receiving progestins, OH plus TVS would eliminate \nunnecessary routine endometrial sampling. The collective \nadvantages of OH include \nin vivo observation of the entire \nendometrial cavity, vessel morphology and distribution, and \naccurate information about non-vascular structures that may \nnot be accessible by blind biopsies.\n22\nPractical methods to examine the different mechanisms \nof action of POCs include simple speculum examination \nto detect viscid cervical mucus, TVS, hormonal assays to \ndiagnose inhibited ovulation and endometrial thickness, and \ninvasive endometrial tissue sampling for histopathological \nexamination. In modern practice, women require a simpler  \nand less invasive method than painful endometrial curettage.  \nIn this study, the hysteroscopic assessment of endometrial \nthickness was consistent with preoperative TVS and histop- \nathology in all cases. Since both TVS and OH findings were \nconsistent, we believe that they would be complementary in \nthe quick assessment of endometrial abnormalities. Specific \nclinical characteristics of the patients should be considered, \nas previously recommended.\n21\n However, the advantages of \nOH over TVS include being the gold standard diagnostic \ntool for observing tiny lesions or abnormal vasculature and \nassessing FT function.\nNormal and thin EM were diagnosed in 36 (51.4%) and \n27 cases (38.3%) using POCs, respectively. Moreover, en -\ndometrial polyps were easily diagnosed and treated in three \ncases (4.3%). In this study, a simple and practical method \nwas used to assess endometrial thickness by applying gentle \npressure along the entire posterior wall with the tip of the \ntelescope to check for endometrial furrow formation. Simi -\nlarly, OH offers a visual assessment of the EM vasculature. \nIt was able to diagnose a normal endometrial vasculature \npattern in 45 patients (64.3%) and a congested pattern in \n25 POCs users (34.7%). A hysteroscopic diagnosis of a free \nendometrial cavity or any intrauterine lesion (supported by \nnormal TVS) minimizes the burden on the pathologist by \neliminating unnecessary samplings.\n22\n Moreover, it also alle-\nviated invasive endometrial sampling pain, which was expe-\nrienced by 49 (70%) and 50 patients (71%) in groups A and \nB, respectively. Furthermore, it alleviated the anxiety and \nstress of waiting several days for biopsy results. In addition \nto the fact that these women are usually young and receiv -\ning progestins, OH plus TVS would eliminate unnecessary \nroutine endometrial sampling. The collective advantages of \nOH include \nin vivo  observation of the entire endometrial \ncavity, vessel morphology and distribution, and accurate \ninformation about nonvascular structures that may not be \naccessible by blind biopsies.\n23\nRegarding the effect of POCs on the FT, it is postulated \nthat they may lead to a 40-50% reduction in the epithelial \nciliary beat frequency and decreased contractions of the \nlongitudinal muscular layer of the human FT compared \nwith the baseline value. The former has been proven in an \nanimal study\n24\n while the latter has been proven in an in vi-\ntro study.\n25\n In a pilot study, repeated hysterosalpingography \n(HSG) was used to confirm functional proximal FT occlu -\nsion in women using depot MPA.\n26\n Repeated HSG pain, \nirradiation, and invasiveness, in addition to ethical contro -\nversies, are the significant disadvantages of this study. For \n\nVol. 21, No. 2, May 2024\n28\nhttps://medsci.jejunu.ac.kr/\nJournal  of  Medicine  and  Life  Science\nthe past decade, our institution has been interested in study \nof the FT function utilizing hysteroscopy.\n11-13,16\n The unique \nadvantage of using OH to assess FT in POCs users was ad -\ndressed in this study. This confirmed the postulated effect \nof POCs on the FT by statistically significant negative peri-\nstalsis and negative bubble flow tests in the proximal part \nof the FT, which are mostly attributed to the direct effect of \nprogestins on the FT. In this study, negative bubble flow test \nresults in POCs users indicated that the passage of bubbles \nto the FT is not a passive phenomenon but is controlled by \nthe peristalsis of the proximal part of the FT. This observa -\ntion is supported by using the lowest intrauterine pressure \nsufficient for proper visualization and observing bubbles \nwaiting for some time at the ostia, which contributed to \nreporting at 1 and 2 minutes (Table 4). Lastly, OH was diag-\nnosed as viscid cervical mucus in 26 of the 32 cases using \nPOP. To the best of our knowledge, this is the first study to \ndocument the mechanisms of action of POCs utilizing OH, \nincluding the \nin vivo  observation of the entire endometri -\nal cavity, endometrial thickness, vessel morphology and \ndistribution, accurate assessment of FT function, and easy \ndetection of viscid cervical mucus. An important issue was \nselecting a control group without hormonal treatment to \navoid bias in interpreting the endometrial and FT changes \nwith the use of POCs.\nDifferent forms of AUB with POCs contribute to the high \nincidence of discontinuation and subsequent undesired preg-\nnancy. In addition to systemic hormonal imbalances, local \nendometrial causes have been suggested. Despite well-doc-\numented endometrial thinning in most cases at the EM \nlevel, there is a paradoxical increase in vascular defects that \ncommonly cause occasional spotting. Bleeding with POCs \nmay be attributed to fragile vessels due to a lack of stromal \nsupport, secondary to progestogen-induced endometrial \ndysfunction, which inhibits uterine vascular smooth muscle \ncell survival.\n27\n A human and animal study confirmed that \nendometrial thin-walled, hyperdilated, fragile microvessels \nwere due to reduced proliferation of human and guinea pig \nendometrial vascular smooth muscle cells (VSMCs) in cases \nusing long-acting POCs, as confirmed by altered transcrip -\nFigure 2. Management plan of abnormal uterine bleeding in POC regular users. AUB: abnormal uterine bleeding, POC: progestogen-only contra-\nceptive, LNG: levonorgestrel, IUS: intrauterine system, COC: combined oral contraceptive, NSAID: nonsteroidal anti-inflammatory drug.\nFree endometrial cavity\nFree adnexae\nSuspected  \nendometrial polyp\n2D-TVS 3D-TVS\nNo polypEndometrial polyp\nOffice hysteroscopy\nNormal endometrial\nvasculature\nCOCs\nExtraction\nWell-placed\nDisplaced or  \nMal-rotated\nYesNO\nHysteroscopic \npolypectomy\nAbnormal endometrial\nvasculature\nSonohysterography \nManagement plan of AUB in POC regular users\nTrans-vaginal ultrasonography (TVS)\nTranexamic acid, diosmin, NSAID\nSystemic hormones:\nestrogen, COCs, norethindrone acetate\n2\nLNG-IUSOvarian cyst\n\n Office hysteroscopy in progestin-only contraception\n29\nhttps://medsci.jejunu.ac.kr/\nAtef Darwish, Ibrahim Mohammad, Samuel Gendy, Dina Darwish, Mohammad Ramdan \ntion of some genes in the cultured endometrium.\n28\n Others \nhave suggested using transvaginal color and pulsed Doppler \nultrasonography as tools to detect increased blood perfusion \nin the uterine and spiral arteries, a significant decrease in \nRI and PI, and increased blood flow in the subendometri -\nal vessels.\n29\n Despite interesting Doppler studies, clinical \ndecision-making cannot be based on these findings. More \nresearch is needed to gain a deeper understanding of the \nmechanisms and establish long-term interventions to man -\nage bleeding irregularities in POCs.\n18\n The use of OH in this \nstudy shortens this narrative. It properly assesses the endo -\nmetrial thickness and vasculature and excludes any intra -\nuterine organic causes within a few minutes. Interestingly, it \ncan diagnose a congested endometrium with easy bleeding, \nconfirming a local vascular cause that may respond to vas -\ncular supportive therapy. In this study, normal endometrial \nthickness and vasculature diagnosed by OH were valuable \nnegative findings, as they directed the gynecologist towards \nsystemic causes such as improper or irregular use. In this \nstudy, hysteroscopic access to the cornual parts of the en -\ndometrial cavity was successful in more than 90% of the \ncases, despite AUB in many of them. This can be attributed \nto the use of a simple pump to wash blood clots from the en-\ndometrial cavity, as described in a previous study.\n10\nDespite the findings of this study being descriptive and  \nbased on OH, incorporating TVS and endometrial sampl-  \ning would provide additional insights into the mechanism. \nHowever, the heterogeneity of types, doses, duration, \nand routes of administration of POCs, the small sample \nsize, including only symptomatic POCs users, the infreq-  \nuent patient attendance for follow-up, and the lack of \nlaparoscopic control of the impact of POCs on FT function \ndue to ethical considerations were the main limitations. \nMoreover, this study lacks an assessment of the potential \nconfounders of AUB. More studies on the endometrial \npattern of individual types of POP are required, particularly \nafter the introduction of the new generation of high-dose 4 \nmg drospirenone-only pills (DOP), which are administered \nfor 24 days with 4 days off.\n30\n Additionally, hysteroscopic \nassessment of the endometrium is subjective, with possible \nintra-observer variations. Finally, the heterogeneity of group  \nB is an additional limitation. This study calls for a univer-  \nsally agreed-upon classification of normal and abnormal \nendometrial vasculature in POCs users and non-users to \nfacilitate appropriate interventions. We invited interested \nhysteroscopists to share their research on normal and \nabnormal endometrial vasculature in different types of \nPOCs, as observed by OH, such as dilated, tortuous, and \nworm-like capillaries (endometrial vascular dystrophy), \nbelieved to be caused by thrombosed capillaries.\n31\n The \nwidespread use of OH in clinics, attending concise training \ncourses, and increasing the orientation of gynecologists \non technical skills would enhance their use in the field of \ncontraception for the proper study of endometrial changes  \nand help explain some related side effects. In conclusion, \nusing OH as a simple diagnostic tool in cases of POCs \nwould contribute to a better understanding of the mechani- \nsms of endometrial and FT effects and help explain some \nlocal endometrial causes of AUB. Furthermore, this assures \nthat the combined TVS and OH restrict the need for routine \ninvasive endometrial sampling for POCs users. In the era \nof precision medicine, the incorporation of OH into the \ndiagnostic work-up algorithm for the management of AUB \nin regular POC users would help construct an individualized \nmanagement plan, as shown in Fig. 2. \nORCID\nAtef Darwish, https://orcid.org/0000-0003-0167-9337\nREFERENCES\n  1. Monterrosa-Castro A, Redondo-Mendoza V , Monterrosa-Blanco \nA. Current knowledge of progestin-only pills. Electron J Gen Med \n2021;18:em320.\n  2. Ayalon NV , Segev L, Samson AO, Yagel S, Cohen SM, Green T, \net al. Norethisterone reduces vaginal bleeding caused by progester-\none-only birth control pills. J Clin Med 2022;11:3389.\n  3. Dilbaz B, Bülbül M, Dilbaz S, Yılmaz N, Sanisoğlu S. The efficacy, \nacceptability and continuation of postpartum, post-abortive pro-\ngestin-only pill: a pioneering prospective multicentric study from \nTurkey. 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