{"paper_id":"451127c0-0b94-4d71-a0e9-9c7af5f1334f","body_text":"Presence of intrauterine\nfluid in women with a large\nniche is not associated with\nad i f f e r e n c ei n\nendometrial thickness\nOBJECTIVE\nA long-term complication of a Cesarean section (CS) is a Ce-\nsarean scar defect, or uterine niche. Over 60% of women\ndevelop a niche, and 24% of these women have a large niche\n(1). A niche can cause gynecological symptoms such as\ndysmenorrhea and spotting ( 2).\nFurthermore, a niche may have a negative impact on\nfertility. Poor outcomes in fertility treatments after CS is a\nconcern. Women with a previous CS have a lower ‘live birth\nrate’ in in vitro fertilization or intracytoplasmic sperm injec-\ntion cycles than the women who deliver vaginally (3). In addi-\ntion, women with a niche have a signi ficantly lower\npregnancy rate than the women without a niche; 37.5% vs.\n47.6% (4). The low pregnancy rate despite equal embryo qual-\nity suggests that embryo implantation may be compromised.\nSuccessful implantation of the embryo requires a recep-\ntive endometrium and an attachment of the embryo. Previ-\nous studies show that intrauterine fluid (IUF) because of a\nhydrosalpinx reduces reproductive outcomes signi ficantly\nby affecting the thickness and composition of the endome-\ntrium (5). A thinner endometrium is associated with reduced\nreproductive outcomes after in vitro fertilization or intracy-\ntoplasmic sperm injection ( 6). As 46% of niches are associ-\nated with IUF ( 2), we hypothesized that niche-related –IUF\ncompromises the endometrial thickness and could be an in-\ntermediate factor for the negative impact of a niche on\nfertility.\nSTUDY DESIGN\nA prospective cohort study was performed in the Amsterdam\nUniversity Medical Center (medical ethics committee\nnumbers: 2011.297, 2018.009). All women with a large niche,\ndefined as a residual myometrial thickness (RMT) of <3m m\nor an RMT <50% of the adjacent myometrial thickness, reg-\nular menstrual cycle, and unexplained infertility (as de fined\nby the World Health Organization), who visited our\nout-patient clinic between 2011 and 2021 were included.\nExclusion criteria were as follows: use of medication likely\nto influence endometrial thickness; hydrosalpinx; or intraca-\nvitary irregularities.\nDuring the first consultation, baseline characteristics were\nrecorded and participants were examined by transvaginal ul-\ntrasound performed by experienced gynecologists. Before\nanalysis, all measurements were veri fied by reviewing the\nrecorded sonographic evaluations by 2 researchers (S.K.M.\nand B.P.). If required, a third person (J.H.) was consulted and\ndisagreements were discussed until consensus was reached.\nThe niche was measured according to the niche measurements\nguideline (1). Double endometrial thickness was measured in\nthe midsagittal plane, as the maximum distance between the\n2 interfaces of endometrial–myometrial junction. The presence\nof adenomyosis was scored based on the Morphological Uterus\nSonographic Assessment (MUSA) criteria by van den Bosch (7).\nWhen IUF was present, thickness of anterior and posterior wall\nendometrium was measured thereby excluding the IUF.\nWomen with a niche and infertility were divided into 2\ngroups based on the presence of IUF, de fined as fluid in the\nuterine cavity independent of the presence of fluid located\nin the niche ( Fig. 1 A and B). The outcome of this study was\nendometrial development as measured by endometrial\nthickness.\nFor statistical analysis, IBM SPSS Statistics v.26 (2019)\nwas used. Tests were performed 2-sided and were considered\nstatistically significant with P< .05. A linear regression anal-\nysis, with adjustment for the day of the menstrual cycle, dura-\ntion of infertility, and RMT was performed.\nRESULTS\nA total of 141 women met the inclusion criteria. Table 1 pre-\nsents the baseline characteristics of 103 (73%) women without\nand 38 (27%) women with IUF. Baseline characteristics of\nboth groups were comparable except for RMT and duration\nof infertility. The duration of infertility in the group with\nIUF was significantly longer; 27 months (interquartile ranges\n[IQRs], 19 –42) vs. 24 months (IQR, 16 –36), P¼ .02. The vol-\numes of the niches were comparable in both groups.\nNo statistically signi ficant difference in thickness of the\nendometrium was found between the 2 groups. The median\nendometrial thickness of women without IUF was 6.6 mm\n(IQRs, 4.5 –9.0) compared with 6.0 mm (IQRs, 4.5 –8.1) in the\ngroup with IUF, P¼ .25 (Fig. 1C). Additional linear regression\nanalysis with adjustment, found no signi ficant relation be-\ntween IUF and endometrial thickness neither ( b 0.96, P¼ .53).\nA sub analysis of women in the luteal phase (n ¼ 62)\nshowed a similar trend, the median endometrial thickness of\nwomen without IUF was 7.8 mm (IQR, 5.7 –10.2) compared\nwith 7.1 mm (IQR, 4.8 –9.5), P¼ .46 (Fig. 1D).\nOverall, the presences of adenomyosis was not signi fi-\ncantly different between the groups, except for fan-shaped\nshadowing, which was more pronounced in the group without\nIUF ( Table 1 ). Possibly the presence of more pronounced\nfibrosis or IUF masks the typical shadowing, as there was\nno difference in translesional vascularity and other adeno-\nmyosis features.\nCONCLUSION\nThe presence of IUF in women with a niche was not associated\nwith a signi ficant difference in endometrial thickness. How-\never, we noted a longer duration of infertility at baseline in\nwomen with a niche when IUF was present. Prospective\nstudies of endometrial cellular composition, secretome and\nfunction as well as differences in uterine microbiome and\nS.J.M.K.M. has nothing to disclose. B.P. has nothing to disclose. J.V. has nothing to disclose. R.A.d.L. has nothing to disclose. E.D.P.U. has nothin g to disclose.\nJ.A.F.H. has nothing to disclose.\n322 VOL. 119 NO. 2 / FEBRUARY 2023\nRESEARCH LETTER\n\nadenomyosis features in women with a large niche in relation\nto reproductive outcome are underway, to shed more light on\nniche related infertility, especially when IUF is present.\nSaskia J.M. Klein Meuleman, M.D.\na,b\nBritt Post, M.D. a\nJolijn Vissers, M.D. a,b\nRobert A. de Leeuw, M.D., Ph.D. a,b\nEmiel D. Post Uiterweer, M.D., Ph.D. a,c\nJudith A.F. Huirne, M.D., Ph.D. a,b,*\na Department of Obstetrics and Gynaecology, Amsterdam\nUniversity Medical Center, Vrije Universiteit Amsterdam,\nAmsterdam, the Netherlands; b Amsterdam Reproduction and\nDevelopment, Amsterdam, the Netherlands; and c Department\nof Obstetrics and Gynaecology, University Medical Center\nUtrecht, Utrecht, the Netherlands\n*Correspondence to: Judith A.F. Huirne, M.D., Ph.D.,\nDepartment of Obstetrics and Gynaecology, Amsterdam\nUniversity Medical Center, Meibergdreef 9, 1105 AZ\nAmsterdam, the Netherlands.\nE-mail address: j.huirne@amsterdamumc.nl\nhttps://doi.org/10.1016/j.fertnstert.2022.11.004\nREFERENCES\n1. Jordans IPM, de Leeuw RA, Stegwee SI, Amso NN, Barri-Soldevila PN, van den\nBosch T, et al. Sonographic examination of uterine niche in non-pregnant\nwomen: a modi fied Delphi procedure. Ultrasound Obstet Gynecol 2019;53:\n107–15.\n2. Vervoort A, Vissers J, Hehenkamp W, Br€olmann H, Huirne J. The effect of lapa-\nroscopic resection of large niches in the uterine caesarean scar on symptoms,\nultrasound findings and quality of life: a prospective cohort study. BJOG\n2018;125:317–25.\n3. Vissers J, Sluckin TC, van Driel-Delprat CCR, Schats R, Groot CJM,\nLambalk CB, et al. Reduced pregnancy and live birth rates after in vitro fertil-\nization in women with previous Caesarean section: a retrospective cohort\nstudy. Hum Reprod 2020;35:595 –604.\n4. Wang L, Wang J, Lu N, Liu J, Diao F. Pregnancy and perinatal outcomes of pa-\ntients with prior Cesarean section after a single embryo transfer in IVF/ICSI: a\nretrospective cohort study. Front Endocrinol (Lausanne) 2022;13:851213 .\n5. Sapmaz T, G €undo/C21gdu LS, Cetin MT, Urunsak IF, Polat S. The ultrastruc-\ntural effects of surgical treatment of hydrosalpinx on the human endome-\ntrium: a light and electron microscopic study. Ultrastruct Pathol 2019;43:\n99–109.\n6. Gao G, Cui X, Li S, Ding P, Zhang S, Zhang Y. Endometrial thickness and IVF\ncycle outcomes: a meta-analysis. Reprod Biomed Online 2020;40:124 –33.\n7. Van den Bosch T, de Bruijn AM, de Leeuw RA, Dueholm M, Exacoustos C,\nValentin L, et al. Sonographic classi fication and reporting system for diag-\nnosing adenomyosis. Ultrasound Obstet Gynecol 2019;53:576 –82.\nVOL. 119 NO. 2 / FEBRUARY 2023 323\nFertility and Sterility®\n\nFIGURE 1\n(A) Image of a uterus with a niche and intrauterine fluid in midsagittal plane using transvaginal ultrasound. (B) Schematic image of the uterus with a\nniche and intrauterine fluid in (a), with n ¼ uterine niche (C) Distribution of endometrial thickness in women without intrauterine fluid ( blue\ntriangles) and women with intrauterine fluid ( green dots ). ( D) Median endometrial thickness in women without intrauterine fluid ( blue) and\nwomen with intrauterine fluid (green) during the luteal phase.\nKlein Meuleman. Niche related intrauterine fluid. Fertil Steril 2022.\n324 VOL. 119 NO. 2 / FEBRUARY 2023\nRESEARCH LETTER\n\nTABLE 1\nBaseline characteristics\nWithout intrauterine fluid\n(n [ 103) With intrauterine fluid (n [ 38) P value\nMean age (y) 34.15 (32.64 –37.11) 34.57 (32.44 –37.01) 0.71\nBMI (kg/m2) 24.39 (21.78 –27.46) 25.18 (22.16 –29.39) 0.30\nSmoking (n (%)) (n ¼ 101)5 (4.95) (n ¼ 36)4 (11.11) 0.24\nNumber of CS 1.17 /C6 0.45 1.16 /C6 0.44 0.74\nNumber of miscarriages 0.50 /C6 1.06 0.79 /C6 1.32 0.16\nDuration of infertility (m) 24.00 (16 –36) 27.00 (19 –42) 0.02\nCycle day 14.00 (8.0 –18.00) 11.00 (7.0 –20.0) 0.43\nPosition of uterus (%) 0.08\nAvF 43 (41.7) 22 (57.9)\nRvF 34 (33.0) 7 (18.4)\nStretched 11 (10.7) 7 (18.4)\nExtreme RvF 15 (14.6) 2 (5.3)\nNiche volume (mm\n3)( n ¼ 97) (n ¼ 38) 0.95\n353.40 (192.65–861.99) 268.46 (165.40 –556.19)\nRMT (mm) 1.0 (0.1 –1.5) 1.50 (0.88 –2.13) 0.01\nAny MUSA criterion for\nadenomyosis present\n(n ¼ 75) 40 (53.3) (n ¼ 26) 17 (65.4) 0.29\nInterrupted junctional zone present,\nn( % )\n(n ¼ 75) 8 (10.7) (n ¼ 26) 2 (7.7) 0.50\nIrregular junctional zone present,\nn( % )\n(n ¼ 75) 15 (20.0) (n ¼ 26) 3 (11.5) 0.26\nSub endometrial lines and buds\npresent, n (%)\n(n ¼ 75) 18 (24.0) (n ¼ 26) 3 (11.5) 0.14\nTranslesional vascularity present,\nn( % )\n(n ¼ 75) 21 (28.0) (n ¼ 26) 6 (23.1) 0.63\nFan-shaped shadowing present,\nn( % )\n(n ¼ 75) 15 (20.0) (n ¼ 26) 1 (3.8) 0.04\nHyperechoic islands present, n (%) (n ¼ 75) 25 (33.3) (n ¼ 26) 6 (23.1) 0.33\nCysts in myometrium present, n (%) (n ¼ 75) 10 (13.3) (n ¼ 26) 5 (19.2) 0.33\nAsymmetrical thickening of\nmyometrium present, n (%)\n(n ¼ 75) 15 (20.0) (n ¼ 26) 7 (26.9) 0.46\nNote: Data are presented as mean (/C6 SD) or median (interquartile range) or counts (%). BMI ¼ body mass index, AvF ¼ anteverted flexed, MUSA ¼ Morphological Uterus Sonographic Assessment,\nRvF¼ retroverted flexed, RMT ¼ residual myometrial thickness\nKlein Meuleman. Niche related intrauterine fluid. Fertil Steril 2022.\nVOL. 119 NO. 2 / FEBRUARY 2023 325\nFertility and Sterility®","source_license":"CC0","license_restricted":false}