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Effect of unilateral tubal abnormalities on the results of intrauterine inseminations

      Abstract

      A total of 101 patients with one normal tube were compared with 117 patients with two normal tubes to assess the effect of unilateral tubal abnormalities on the results of intrauterine inseminations. The clinical pregnancy and live birth rates seemed to reduce by one-half in almost all types of abnormality, suggesting that these patients should be preferentially treated with IVF.

      Keywords

      Introduction

      Intrauterine insemination (IUI) is one of the first lines of infertility treatments and assisted reproductive techniques. According to the French registry, the mean delivery per insemination rate is 10.7%, but with wide variations from one centre to another (4.4% to 19%) (
      • Agence de la Biomédecine
      Evaluation des résultats des laboratoires d'assistance médicale à la procréation pratiquant l'insémination artificielle intra-uterine in vitro en France.
      ). One possible explanation could be the heterogeneity of the treated population, and especially the status of the Fallopian tubes, as the place of IUI when only one Fallopian tube is functioning normally is still under debate.
      The aim of the study was to evaluate the results of IUI carried out in women with a unilateral tubal abnormality through a retrospective study.

      Materials and methods

      Patients

      A total of 818 couples who had at least one IUI (total: 1880 cycles) between January 2007 and December 2012 at the Toulouse University Hospital were included in the study. The indications of IUI were as follows: ovulation disorder (20%), endometriosis (5%), sperm abnormalities (18%), male and female causes (1%), use of donor sperm (10%) and unexplained infertility (46%). Inclusion criterion was all patients having at least one IUI from January 2007 to December 2012 in the Toulouse University Hospital.

      Tubal evaluation-tubal patency

      Before starting IUI treatment, tubal permeability was assessed for all patients using hysterosalpingography. All patients with a tubal abnormality suspected at hysterosalpingography (n = 180) underwent laparoscopy, which seemed to be normal in 79 cases (44%). During this laparoscopy, 16 patients (9%) had one tube removed owing to hydrosalpinx and 11 (6%) had tubal surgery.

      Intrauterine inseminiation procedures

      Ovarian stimulation used a combination of recombinant FSH (Gonal F, Merck, Lyon, France or Puregon, MSD, Paris, France) and gonadotrophin-releasing hormone (GnRH) antagonist (Cetrotide 0.2 5 mg, Merck, Lyon, France or Orgalutran, MSD, Paris, France). Ovulation was triggered with recombinant HCG (Ovitrelle, Merck, Lyon, France) when at least one follicle measured 18 mm or more. The cancellation criteria depended on the woman's age: more than one follicle measuring 15 mm or more in women aged less than 27 years; more than two follicles in women aged between 27 and 37 years; and more than three follicles in women aged over 37 years. Insemination was carried out 36 h after HCG injection. Clinical pregnancy was defined as the presence of a fetal heartbeat 7 weeks after insemination. Live birth was defined as the delivery of at least one live born infant.

      Statistical analysis

      Data were extracted from the clinical database Gynelog used in our department. Statistical analyses were carried out using StatView software (Abacus Concepts Inc., Berkeley, CA). Data are means ± SD or median (range) according to the normality of the data. Percentages were compared using chi-square test. Means were compared using the Student's t-test, and medians were compared using the Mann–Whitney test according to the normality of data distribution. Logistic regression analysis was carried out using SAS 9.3 software (SAS Institute, Cary, NC).
      The study was approved by Toulouse University Hospital's Clinical Research Ethics Committee on 30 November 2016 (reference number 121116). No funding was obtained for this study.

      Results

      As shown in Table 1, the demographic parameters (age, body mass index, number of inseminated motile spermatozoa, number of IUI cycles, percentage of cigarette smokers) were not different between the group with two normal tubes and the groups with unilateral abnormalities. In the studied population, unilateral tubal abnormalities represented 12.3% of patients. Overall, 287 clinical pregnancies were achieved out of 276 deliveries (85% singletons, 15% twins and 0.3% triplets). In addition, two ectopic pregnancies occurred in the group of women who had previous ectopic pregnancies. The presence of unilateral tubal abnormality was associated with a reduction by about one-half of clinical pregnancy and live birth rates. The cumulative clinical pregnancy rates were significantly decreased for all types of unilateral tubal abnormalities: P < 0.001 for one absent tube; P < 0.05 for one patent tube (the other not occluded but altered or for one occluded), except in women who had previous tubal surgery and previous ectopic pregnancies (there were few cases of these latter abnormalities). The cumulative live birth rate, however, was significantly decreased only in the group that had one tube removed (P < 0.001). Compared with patients with two normal tubes, the raw odds ratio for cumulative live birth for those with one abnormal tube was 0.38 with 95%. When adjusted for age, BMI, infertility duration and number of inseminated spermatozoa, the odds ratios for cumulative live birth were 0.22 to 0.64, and 0.377 [0.21 to 0.64]. No difference was found in live birth rate when comparing distal and proximal abnormalities (19% [6/32] and 22% [5/23], respectively; non-significant data were not available for three patients).
      Table 1Results of intrauterine insemination according to tubal status.
      Data are means ± SD or median [range] according the normality of the distribution.
      Two normal tubesOne abnormal tube
      TotalOnly one tube; the other removedOne patent tube the other not occluded but alteredOne occludedPrevious tubal surgeryPrevious ectopic pregnancyStatistical comparison versus two normal tubes
      Number of patients7171011635231116
      Age (years)34.3 ± 4.334.6 ± 3.933.9 ± 4.833.6 ± 3.636.2 ± 3.834.8 ± 4.035.8 ± 2.7NS
      Infertility duration (months)52 [15–204]56 [13–145]50 [23–112]50 [16–99]59 [22–115]14 [24–117]66 [13–145]NS
      BMI (kg/m2)21.9 ± 3.021.7 ± 3.023.3 ± 3.320.9 ± 3.322.2 ± 3.120.6 ± 2.720.6 ± 2.7NS
      Smoking status, n (%)
       Never smoker416 (58)61 (60)12 (75)19 (54)13 (57)6 (55)12 (75)NS
       Past smoker144 (20)23 (23)2 (13)11 (31)5 (22)3 (27)0
       Current smoker157 (22)17 (17)2 (13)5 (14)5 (22)2 (18)4 (25)
      Number of IUIs2.3 ± 1.42.3 ± 1.22.2 ± 1.22.4 ± 1.22.3 ± 1.31.7 ± 1.32.4 ± 1.3NS
      Number of inseminated motile spermatozoa (x106)10.1 (0.2–295)12.1 (1.0–161.5)9.0 (2.9–29.7)15.0 (1.2–116.0)7.1 (1.0–91.2)27.2 (3.1–161.5)14.9 (1.1–48.5)NS
      Clinical pregnancy rate per cycle, % (n)16 (269/1651)8 (18/229)
      Data with the same superscript are statistically diffferent.
      0 (0/35)
      Data with the same superscript are statistically diffferent.
      9 (7/82)8 (4/52)14 (3/21)10 (4/39)
      Data with the same superscript are statistically diffferent.
      P < 0.001

      Data with the same superscript are statistically diffferent.
      P < 0.01
      Live birth rate per cycle, % (n)16 (258/1651)8 (18/229)
      Data with the same superscript are statistically diffferent.
      0 (0/35)
      Data with the same superscript are statistically diffferent.
      9 (7/82)8 (4/52)14 (3/21)10 (4/39)
      Data with the same superscript are statistically diffferent.
      P < 0.01

      Data with the same superscript are statistically diffferent.
      P < 0.05
      Cumulative clinical pregnancies, n (%)269 (38)18 (18)
      Data with the same superscript are statistically diffferent.
      0
      Data with the same superscript are statistically diffferent.
      7 (20)
      Data with the same superscript are statistically diffferent.
      4 (17)
      Data with the same superscript are statistically diffferent.
      3 (27)4 (25)
      Data with the same superscript are statistically diffferent.
      P < 0.001

      Data with the same superscript are statistically diffferent.
      P < 0.01

      Data with the same superscript are statistically diffferent.
      P < 0.05
      Cumulative live births, n (%)258 (36)18 (18)
      Data with the same superscript are statistically diffferent.
      0
      Data with the same superscript are statistically diffferent.
      7 (20)4 (17)3 (27)4 (25)
      Data with the same superscript are statistically diffferent.
      P < 0.001

      Data with the same superscript are statistically diffferent.
      P < 0.01
      BMI, body mass index; IUI, intrauterine insemination.
      a Data are means ± SD or median [range] according the normality of the distribution.
      b,c,d Data with the same superscript are statistically diffferent.

      Discussion

      The present study is the largest conducted on this subject as it compared 101 tubal abnormalities with 717 controls. Unilateral tubal abnormalities seemed to be associated with a dramatic decrease in live birth rate, suggesting that IVF should be the preferential treatment in these cases. Similar results have been reported by
      • Berker B.
      • Sukur Y.E.
      • Kahraman K.
      • Atabekoglu C.S.
      • Sonmezer M.
      • Ozmen B.
      • Ates C.
      Impact of unilateral tubal blockage diagnosed by hysterosalpingography on the success rate of treatment with controlled ovarian stimulation and intrauterine insemination.
      , with a drop in the pregnancy rate from 44.7% in control to 26.3% in the case of unilateral tubal blockage. Unlike our findings, the decrease occurred only in distal blockage.
      • Farhi J.
      • Ben-Haroush A.
      • Lande Y.
      • Fisch B.
      Role of treatment with ovarian stimulation and intrauterine insemination in women with unilateral tubal occlusion diagnosed by hysterosalpingography.
      also found no effect of proximal blockage, the effect mainly occurring in distal cases. In contrast,
      • Yi G.
      • Jee B.C.
      • Suh C.S.
      • Kim S.H.
      Stimulated intrauterine insemination in women with unilateral tubal occlusion.
      and
      • Lin M.H.
      • Hwu Y.M.
      • Lin S.Y.
      • Lee R.K.
      Treatment of infertile women with unilateral tubal occlusion by intrauterine insemination and ovarian stimulation.
      found no difference in pregnancy rate whatever the tubal status. These discrepancies could be explained by different definitions of tubal abnormalities, as unilateral blockages represent 12.3% of the whole population in our study, whereas, in other studies, it is 24%, 35%, 25% and 19%, respectively.
      The pregnancy rate in women with one patent tube was about one-half that in women with two patent tubes, which could suggest that the pregnancies were achieved when ovulation occurred on the healthy side. As we did not record the side of the patent tube and the leading follicle, this hypothesis cannot be confirmed; however if it is correct, it would indicate that IUI should be cancelled in one-half of cases.
      No pregnancies occurred in women with only one tube. One explanation could be that most of them (10/16) had a salpingectomy for hydrosalpinx, probably reflecting a severe tubal inflammatory process and, therefore, the contralateral tube can be functionally affected.
      These data suggest that, in cases of unilateral tubal abnormalities, the practice of IUI must be questioned, mainly when time is counted owing to female age or low ovarian reserve.

      Acknowledgement

      We would like to thank Dr Walschaerts for her assistance with the statistical analysis.

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        Evaluation des résultats des laboratoires d'assistance médicale à la procréation pratiquant l'insémination artificielle intra-uterine in vitro en France.
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      Biography

      Dr Cochet received her medical degree in 2012 from the Toulouse Medical University, France, where she completed her residency training in gynaecology and reproductive medicine. She is currently working at the Muret clinic as a specialist in Reproductive Medicine.