{"paper_id":"7a43f447-0e30-40c4-a01e-607d16dbd242","body_text":"Intrauterine insemination (IUI) is an effective and widely\nused treatment that is mainly recommended for male\nfactor, minimal and mild endometriosis, cervical factor\nor unexplained infertility cases. The term unexplained infertility\nincludes infertile pairs whom ovulatory function,\ntubal passage and semen analysis are normal. The procedure\ninvolves the direct delivery of washed spermatozoa\nin order to bypass the cervix and increase the sperm volume\nat the site of fertilisation ( 1 - 4 ).\nIn the literature, the pregnancy rate reported in IUI cycles\nvaries widely from 4-40% ( 5 ,  6 ). This great variation\nmight be related to female age, type and duration of\ninfertility, sperm parameters and technical aspects ( 7 ,  8 ).\nUnder the heading of technical aspects, in particular, the\ncatheter type can possibly influence pregnancy outcomes\nfor IUI ( 9 ). In many recent in vitro fertilisation (IVF)\nstudies, the consistency of the embryo transfer (ET) catheter\nhas been determined to be a considerable factor in the\nsuccess of ET, whereas the influence of catheter type in\nIUI is still controversial( 10 ).\nIn a meta-analysis of 1871 IUI cycles, it was reported\nthat endometrial scratch injury was associated with higher\nclinical pregnancy and ongoing pregnancy rates ( 11 ).\nThe authors suggested that the local endometrial trauma\nand subsequent acute inflammatory process might have\nprompted decidualization and improved the implantation\nrate. On the other hand, Balci et al. reported that the immediate\nuterine contractions induced by tenaculum application\nto the cervix during IUI might enhance sperm\ntransport to the ampulla and result in a higher pregnancy\nrate ( 12 ). In this study, we aimed to investigate whether\nfirm catheter introduction or tenaculum use for IUI might\naffect pregnancy related outcomes through local endometrial\ninjury, induced myometrial contractions, or in via\nother means as suggested above.\n\nThis retrospective study was conducted on a total of 338\nIUI cycles carried out at the Department of Obstetrics and\nGynaecology, Zekai Tahir Burak Women’s Health Education\nand Research Hospital, Ankara, Turkey between 2015\nand 2017. Written informed consent was obtained from the\nparticipants for future use. The patients were assigned to\nthree groups - IUI performed with a soft catheter (group1,\nn=175); firm catheter (group 2, n=100); or with the assistance\nof a tenaculum to ease the introduction (group 3,\nn=63). The Ethics Committee of Zekai Tahir Burak Women’s\nHealth Education and Research Hospital, Ankara,\nTurkey approved this study (reference number: 2017/20),\nwhich was conducted in accordance with the Declaration\nof Helsinki 2013 Brazil version (20796219-724.087).\nInclusion criteria for IUI consisted of unexplained infertility\nwith a minimum duration of one year, age under 35\nyears, normal uterine cavity, at least one patent tube, basal\nfollicle stimulating hormone (FSH) <10 mIU/mL, no history\nof gynaecologic surgery and at least 5 million motile\nspermatozoa for the male partner. The first and subsequent\ncycles were admitted to the study. Exclusion criteria were\ndiminished ovarian reserve and male infertility.\nOvarian stimulation was achieved by recombinant FSH (recFSH; follitropin alfa, Gonal-F,\nSerono, Turkey, Istanbul; follitropin beta Puregon, Organon, Turkey) and human menopausal\ngonadotropin (hMG; Ferring, Turkey) based on the patient’s historical and clinical factors.\nrecFSH andhMG were administered in a low-dose step up stimulation protocol that began on the\nsecond day of the menstrual cycle. Ovarian response was recorded through ultrasound\nexamination of antral follicles and by determination of serum oestradiol (E2) levels.\nOvulation was triggered by human chorionic gonadotropin (hCG) (u-hCG, Pregnyl,\nOrganon,Turkey; rec-hCG, Ovitrelle, Serono, Turkey) when one or two follicles reached a\ndiameter of ≥18 mm.Finally, IUI was carried out after 36 hours of hCG administration.\nSemen was collected by masturbation after 3-5 days of\nsexual abstinence and a few hours prior to the scheduled insemination\ntime. The spermatozoa were washed free from\nthe seminal liquid and prepared for insemination by the\nswim-up technique. The difficulty of the insemination was\ndetermined with respect to the comments of two physicians\nwith the same techniques. For the initial attempt to cannulate\nthe cervix, a soft catheter (Allwin Medical Devices,\nCA, USA) was preferred; thereafter, due to the difficulty\ndegree of introduction, a firm catheter (Technocath Medical\nScientifics, Ankara, Turkey) or tenaculum were used for\nthe insemination. Finally, the sperm sample (0.5-1 mL) was\nslowly injected through the catheter into the uterine cavity.\nApproximately two weeks after insemination, all participants\nunderwent pregnancy tests. The endpoints of the\nstudy were the clinical pregnancy rate (CPR), which was\ndefined as evidence of a gestational sac after more than\nsix weeks gestation confirmed by ultrasound and the live\nbirth rate (LBR), which was defined as the delivery of a live foetus after 20 weeks of gestational age.\nStatistical analysis was performed using SPSS 15.0 for\nWindows (SPSS, Chicago, IL, USA). The Kolmogorov-\nSmirnov test was used to examine continuous variables\nwith normal and abnormal distributions. One-way analysis\nof variance was used for normally distributed continuous\nvariables and the Kruskal-Wallis test for abnormally\ndistributed continuous variables. Nominal variables were\nanalysed by Pearson's chi-square or Fisher's exact test,\nwhen applicable. Continuous variables are presented as\nmean-standard deviation (SD) or median (min–max), and\ncategorical variables are presented as the number of cases\nand percentage. A P value of <0.05 was considered to\nbe significant. Power analysis and sample size calculations\nwere carried out using the G*Power 3.0.10 program\n(Franz Faul, Universität Kiel, Kiel, Germany).\n\nFrom the 361 initial participants, 22 (6.09%) dropped\nout of the study. Therefore, 338 participants were included\nin the study: 175 in group 1 that used a soft catheter,\n100 in group 2 that used a firm catheter and 63 in group\n3 that used a tenaculum to ease the introduction ( Fig . 1 ).\nEnrollement and follow-up of the study subjects.\nTable 1 lists the participants’ demographic characteristics\nand laboratory parameters. There were no significant\ndifferences between groups regarding age, body mass\nindex (BMI), baseline hormone profiles, type and duration\nof infertility. Dose and type of gonadotropin (recFSH\nversus hMG), u-hCG versus rec-hCG utilization for trigger,\nluteal phase support, antral follicle count, number of\nfollicles >17 mm and endometrial thickness on hCG day\nwere comparable in all groups. Total progressive motile\nsperm count (TPMSC) and sperm morphology were also\nsimilar between the groups (P>0.05).\nDemographic characteristics and laboratory parameters of the patients\nData are presented as mean ± SD or n(%). SD; Standard deviation,  a ; One-way\nANOVA test,  b ; Kruskal Wallis test, BMI; Body mass index, FSH; Follicle\nstimulan hormone, LH; Luteinizan hormone, E2: Estradiol, hMG; Human menopausal\ngonadotropine, hCG; Human corionic gonadotropine, and TPMSC; Total progressive\nmotile sperm count. P<0.05 is statistical significant.\nTable 2 summarizes the pregnancy related outcomes. There were 48 clinical pregnancies with a CPR of 14.2% (48/338) and the LBR per cycle was 11.53% (39/338), which was comparable to recent data ( 12 ). The CPR was significantly higher in the firm catheter (19%, 19/100) and tenaculum groups (31.7%, 20/63) compared to the group that used the soft catheter (5.1%,9/175) (P<0.001). Both the live birth/clinical pregnancy [84.2% (16/19), 80.0% (16/20), 77.8% (7/9); P=0.736] and miscarriage/clinical pregnancy [15.8% (3/19), 20.0% (4/20), 22.2% (2/9); P=0.736] were comparable in all groups ( Fig . 2 ).\nPerinatal outcomes of the groups. Group 1; Soft, Group 2; Firm, and Group 3;\nTenaculum.\nPregnancy related outcomes of soft, firm catheter and tenaculum applied patients undergoing IUI treatment\nData are presented as n (%).  * ; Statistically significant, IUI; Intrauterine\ninsemination,  a ; Group 1 versus Group 2, and  b ; Group 1 versus\n3.\n\nIUI is a commonly used cost-effective line of treatment for infertility ( 1 ,  13 ). In the literature, the pregnancy rate of IUI widely varies (e.g.,  4 -40%) ( 5 ,  6 ). This variation in pregnancy rates might be related to many factors, including the type of catheter used. The consistency of the ET catheter has been considered a determining factor in the success of ET procedures, whereas the impact of catheter type on IUI has been not been thoroughly investigated and limited data are available ( 10 ,  14 ).\nIn a study conducted by Smith et al., the pregnancy rates\nwere not statistically different between the soft and firm\ncatheter groups when a gentle technique was used and\nthe technician did not touch the top of the fundus with\nthe catether. ( 15 ). Lavie et al. observed by sonography\nthat the firm catheters disrupted the three layer pattern of\nthe endometrium in some patients who underwent IUI;\nhowever, they reported the same overall pregnancy rate\nwith soft catheters ( 16 ). Similar outcomes were obtained\nin other related IUI studies ( 13 ,  17 ,  18 ). The results of\na Cochrane data analysis indicated that there was no\nevidence of any significant difference between soft and\nfirm catheters for IUI in terms of pregnancy related\noutcomes or adverse events ( 19 ).\nPark et al. reported no significant differences in the\nCPR between non-using and using a tenaculum during\nintrauterine insemination ( 20 ). In contrast, Balci et\nal. suggested that uterine manipulation by applying a\ntenaculum to the cervix increased immediate uterine\ncontractility and resulted in a higher pregnancy rate when\nthey used ultrasound guidance to record the frequency of\nuterine contractions after insemination ( 12 ). Similarly,\nin our study, there was significantly greater CPR in the\nfirm catheter and tenaculum groups compared to the soft\ncatheter group. This difference in the success of the IUI and\nIVF treatments depended on the catheter type, and might\nbe due to the difference between the location and timing\nof events during both procedures. In IUI, fertilisation\ntakes place at the ampulla, away from the endometrium\nthat is presumed to be damaged by a firm catheter. If any\nnegative effect occurs in the uterine cavity during IUI,\nit may be achieved both by the volume of inseminated\nsperm and by the period of time until implantation, which\nis enough for natural recovery. Furthermore, in the course\nof artificial insemination, the uterine contractions induced\nby tenaculum application or by introduction of firm\ncatheter might cause an immediate increase in passage\nof the sperm to the fallopian tubes, shorten the arrival\ntime to the ampulla, and might disappear just before the\nfertilisation ( 14 ,  19 ).\nOn the other hand, endometrial scratch injury is a\ntechnique suggested by several studies to improve\nimplantation rates in women who undergo in vitro\nfertilisation and have histories of recurrent implantation\nfailure (RIF). Its application in IUI is less common. This\nprocedure consists of applying a local endometrial travma\nto induce an acute inflammatory process and release of\ngrowth factors or proinflammatory cytokines, which\narepresumed to improve decidualization and a subsequent\nsuccessful implantation ( 21 ,  22 ). In a meta-analysis of\n1871 IUI cycles, it was reported that endometrial scratch\ninjury was associated with a higher CPR (OR 2.27) and\nongoing pregnancy rate (OR 2.04) in comparison with\nthe controls ( 11 ). Therefore, we suggest that inserting a\nfirm catheter into the uterine cavity might have induced a\nlocal endometrial trauma and a subsequent inflammatory\ncascade, which resulted in a higher pregnancy rate\ncompared to the gentle touch with the use of a soft catheter.\nThe limitations of this study are its retrospective\ndesign and small sample size. The primary aim of this\nstudy was to determine the difference in CPR between\ngroups. According to the post hoc power calculation,\nourgroup sample sizes of 175, 100 and 63 achievedan\n80% power to detect a difference of 0.039 between the\nnull hypothesis, which both group proportions were 0.124\nand the alternative hypothesis that the proportion in the\nother group was 0.254 with a significance level of 0.05.\n\nThis study showed that the application of a tenaculum\nor insertion of a firm catheter during the IUI might result\nin a higher CPR but does not alter LBR results. Further\nrandomized prospective studies would be necessary to\nassess the long-term effects of catheter type and tenaculum\nuse on IUI outcome.","source_license":"CC-BY-4.0","license_restricted":false}