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Risk of pelvic inflammatory disease after intrauterine insemination: a systematic review

Published:November 24, 2017DOI:https://doi.org/10.1016/j.rbmo.2017.11.002

      Abstract

      The aim of this study was to ascertain the incidence of pelvic inflammatory disease (PID) after intrauterine insemination (IUI). A systematic review was conducted using three different approaches: a search of IUI registries; a search of published meta-analyses; and a search of prospective randomized trials. Search terms were ‘IUI’, ‘complications’, ‘infection’ and ‘PID’. Two IUI registers were identified that met the inclusion criteria, totalling 365,874 cycles, with 57 PID cases being reported. The post-IUI PID rate was 0.16/1000 (95% CI 0.2 to 0.3/1000). The frequency was higher in husband sperm cycles (0.21/1000) (28/135,839) than in donor sperm cycles (0.03/1000) (1/33,712) (P < 0.05; OR 6.95). Nineteen meta-analyses were retrieved, which included 156 trials, totalling 43,048 cycles, with no PID case being reported. Seventeen prospective clinical trials published between 2013 and 2014 were identified, totalling 4968 cycles; no PID case was reported. The reported rate of post-IUI clinical PID is low (0.16/1000), about 40% higher than reported in the general population of women during their reproductive life. No antibiotic prophylaxis should be recommended unless there is an associated risk factor.

      Keywords

      Introduction

      Intrauterine insemination (IUI) is a widely used procedure. According to the European Society of Human Reproduction and Embryology register, more than 200,000 cycles are carried out in Europe every year, and about 175,000 of them correspond to the sperm of the husband or partner (
      • Calhaz-Jorge C.
      • de Geyter C.
      • Kupka M.S.
      • de Mouzon J.
      • Erb K.
      • Mocanu E.
      • Motrenko T.
      • Scaravelli G.
      • Wyns C.
      • Goossens V.
      European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE)
      Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE.
      ). Common complications of IUI include multiple pregnancy and ovarian hyperstimulation syndrome. Pelvic inflammatory disease (PID) has been reported as a rare complication of IUI, but no data about its expected frequency are available.
      Severe complications are associated with PID, and some of them are especially relevant in women with unfulfilled fertility, such as tubal damage, tubo-ovarian abscess and even ovariectomy. About 15% of PID occurs after procedures that break the cervical mucus barrier (
      • Rock J.A.
      • Jones H.W.
      Pelvic inflammatory disease.
      ,
      • Terao M.
      • Koga K.
      • Fujimoto A.
      • Wada-Hiraike O.
      • Osunaga Y.
      • Yano T.
      • Kozuma S.
      Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease.
      ,
      • Weledji E.P.
      • Elong F.
      Small bowel obstruction and perforation attributed to tubo-ovarian abscess following ‘D’ and ‘C’.
      ). On occasions, PID may develop after certain procedures, such as hysterosalpingography, hysteroscopy, endometrial biopsy, oocyte recovery or even embryo transfer (
      • Pereira N.
      • Hutchinson A.P.
      • Lekovich J.P.
      • Hobeika E.
      • Elias R.T.
      Antibiotic prophylaxis for gynecologic procedures prior to and during the utilization of assisted reproductive technologies: a systematic review.
      ). Antibiotic prophylaxis, however, is not recommended in any of these procedures unless there is a concomitant risk factor (
      • Pereira N.
      • Hutchinson A.P.
      • Lekovich J.P.
      • Hobeika E.
      • Elias R.T.
      Antibiotic prophylaxis for gynecologic procedures prior to and during the utilization of assisted reproductive technologies: a systematic review.
      ,
      • Van Eyk N.
      • van Schalkwyk J.
      Infectious diseases committee. antibiotic prophylaxis in gynaecologic procedures.
      ).
      In some cases of IUI, the introduction of the catheter through the cervical canal and the release of washed sperm could prompt the ascension and spread of cervical microorganisms into the uterus and the tubes. It is well known that ascension of microorganisms is the main mechanism of PID genesis (
      • Paavonen J.
      • Westrom L.
      • Eschenbach D.
      Pelvic inflammatory disease.
      ).
      Some case reports on the occurrence of PID after IUI have been published (
      • Kolb B.A.
      • Mercer L.
      • Peters A.J.
      • Kazer R.
      Abscess following therapeutic insemination.
      ,
      • Moradan S.
      A ruptured tubo-ovarian abscess after intrauterine insemination; a case report.
      ,
      • Sable D.B.
      • Yanushpolsky E.H.
      • Fox J.H.
      Ruptured pelvic abscess after intrauterine insemination: a case report.
      ). In a literature review,
      • Sacks P.C.
      • Simon J.A.
      Infectious Complications of Intrauterine Insemination: a case report and literature review.
      concluded that, after IUI, PID frequency was 6.8/1000; however,
      • Speroff L.
      • Glass R.H.
      • Kase N.G.
      Male infertility.
      cite a frequency close to 1/500. The clinical impression, however, is that the frequency is much lower.
      The occurrence of PID after IUI is a rare complication, and no reliable data on its frequency have been published; therefore, it is difficult to give exact information to patients, and to make decisions about prophylactic antibiotic therapy.
      The aim of our study was to determine the frequency of PID after IUI on the basis of a literature search of large case studies, using three complementary analyses: data from IUI registers where PID is considered; meta-analyses of IUI reporting on complications; and all IUI prospective studies published between 2013 and 2014. Finally, we compare them with our centre's IUI complication register.

      Materials and methods

      A literature review was conducted on the reported frequency of PID, in relation to the number of cycles carried out and the use of husband or donor sperm. Three different literature searches were conducted in accordance with PRISMA and MOOSE guidelines (
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      The PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ;
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • Olkin I.
      • Williamson G.D.
      • Rennie D.
      • Moher D.
      • Becker B.J.
      • Sipe T.A.
      • Thacker S.B.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group.
      ).

      Retrospective analysis

      We reviewed national and international registers on IUI, and identified cases in which PID had occurred after IUI. The search strategy was carried out in PubMed with the combination of any of the following MeSH descriptors: ‘ART register,’ ‘IUI register,’ ‘intrauterine insemination plus complications,’ ‘intrauterine insemination plus infection’ and ‘artificial insemination plus infection’. The time period for the search was 1965–2015. Only human reports were considered. The abstracts were reviewed by one investigator (KR), who reviewed full-text articles when needed. From that search, only one register was obtained, from California Cryobank (1986–2004) (
      • Broder S.
      • Sims C.
      • Rothman C.
      Frequency of postinsemination infections as reported by donor semen recipients.
      ). A similar search was conducted in Google, both in English and Spanish, and the register of the Spanish Fertility Society (2002–2013) was obtained (Table 1).
      Table 1Pelvic inflammatory disease after intrauterine insemination rate resulting from the published register analysis.
      Sources: Spanish Fertility Society 2002–2013 and California Cryobank, 1986–2004.
      YearPublication yearCountryPartner

      ‰ (PID/cycles)
      Donor

      ‰ (PID/cycles)
      Partner + donor

      ‰ (PID/cycles)
      20022005Spain0.38 (5/13,306)0 (0/3571)
      20032006Spain0.20 (3/15,319)0 (0/3978)
      20042007Spain0.36 (7/19,467)0 (0/4862)
      20052008Spain0.23 (5/22,078)0.2 (1/5075)
      20062009Spain0.17 (4/23,976)0 (0/5790)
      20072009Spain0.09 (2/22,917)0 (0/5917)
      20082010Spain0.11 (2/18,776)0 (0/4519)
      20092011Spain0.1 (3/31,173)
      20102012Spain0.07 (2/28,204)
      20112013Spain0.13 (4/30,800)
      20122014Spain0.10 (3/28,596)
      20132015Spain0.27 (8/29,550)
      1986–20042007USA (California)0.17 (8/48,000)
      Total0.21 (28/135,839)0.11 (9/81,712)0.13 (20/148,323)
      Overall total0.16 (57/365,874)
      PID, pelvic inflammatory disease.
      The California Cryobank is a privately owned sperm bank established in 1977 that provides frozen donor semen worldwide. Physicians and recipients were asked to report any adverse outcomes resulting from insemination as well as pregnancy outcome. Most of the infection reports were made verbally by either the recipient or the insemination centre. Most reports were available days to weeks after the insemination (
      • Broder S.
      • Sims C.
      • Rothman C.
      Frequency of postinsemination infections as reported by donor semen recipients.
      ). In most cases, the diagnosis of PID was made by assessing clinical symptoms (
      • Broder S.
      • Sims C.
      • Rothman C.
      Frequency of postinsemination infections as reported by donor semen recipients.
      ).
      The Spanish Fertility Society Register is curated by the
      • Spanish Fertility Society
      Sociedad Española de Fertilidad. Informes Registro Nacional de Actividad-Registro SEF.
      , and each year includes IVF and IUI results of Spanish fertility centres. At that time, data could not be linked to the corresponding centres. The definition of PID was based on symptoms that required hospitalization. No reference was made to antibiotic prophylaxis in any of the registers.

      Review of meta-analyses

      A PubMed search was conducted using the key words ‘IUI meta-analysis’ from the period 2004–2014 (Table 2 and Supplementary Table S1). From the 50 meta-analyses retrieved, those not addressing IUI, or focusing on HIV, endometriosis or tubal patency, were excluded. Finally, 20 meta-analyses remained, which included 191 individual papers. One of the 20 reports on meta-analysis retrieved (
      • Van den Boogaard N.M.
      • Hompes P.G.
      • Barnhart K.
      • Bhattacharya S.
      • Custers I.M.
      • Coutifaris C.
      • Goverde A.J.
      • Guzick D.S.
      • Litvak P.F.
      • Steures P.N.
      • van der Veen F.
      • Bossuyt P.
      • Mol B.W.
      The prognostic profile of subfertile couples and treatment outcome after expectant management, intrauterine insemination and in vitro fertilisation: a study protocol for the meta-analysis of individual patient data.
      ) was excluded, as it corresponded to the design of a meta-analysis and not to one that had already been conducted (Figure 1). From the 191 remaining articles, 35 of these were excluded because their population was at least partially considered in more than one meta-analysis. Such cases were included only once; if a discrepancy was identified between the reported numbers of cycles, the publication that reported a higher number of cycles was included. No reference was made to antibiotic prophylaxis in any of the meta-analyses.
      Table 2Pelvic inflammatory disease after intrauterine insemination resulting from the review of meta-analysis.
      Meta-analysisCyclesPartner/donorComplicationsInfectionsPID rate (%)
      • Cantineau A.E.
      • Janssen M.J.
      • Cohlen B.J.
      • Allersma T.
      Synchronised approach for intrauterine insemination in subfertile couples.
      3662BothMiscarriages; OHSS; ectopic pregnancy; emltiple pregnancyNR0
      • Luo S.
      • Li S.
      • Jin S.
      • Li Y.
      • Zhang Y.
      Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.
      2577NRMiscarriages; OHSS; ectopic pregnancy; multiple pregnancyNR0
      • Luo S.
      • Li S.
      • Li X.
      • Bai Y.
      • Jin S.
      Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination cycles in women with polycystic ovary syndrome: a meta-analysis.
      333NRMiscarriagesNR0
      • Miralpeix E.
      • González-Comadran M.
      • Solà I.
      • Manau D.
      • Carreras R.
      • Checa M.A.
      Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.
      1886BothMiscarriages; multiple pregnancyNR0
      • Cantineau A.E.
      • Cohlen B.J.
      • Heineman M.J.
      • Marjoribanks J.
      • Farquhar C.
      Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility.
      2557BothMiscarriages; multiple pregnancy; OHSS; ectopic pregnancyNR0
      • Hill M.J.
      • Whitcomb B.W.
      • Lewis T.D.
      • Wu M.
      • Terry N.
      • DeCherney A.H.
      • Levens E.D.
      • Propst A.M.
      Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis.
      1954NRMiscarriagesNR0
      • Zavos A.
      • Daponte A.
      • Garas A.
      • Verykouki C.
      • Papanikolaou E.
      • Anifandis G.
      • Polyzos N.P.
      Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis.
      1125PartnerNRNR0
      • Veltman-Verhulst S.M.
      • Cohlen B.J.
      • Hughes E.
      • Heineman M.J.
      Intra-uterine insemination for unexplained subfertility.
      1026PartnerMiscarriages; multiple pregnancy; OHSS; ectopic pregnancyNR0
      • Van den Boogaard N.M.
      • Hompes P.G.
      • Barnhart K.
      • Bhattacharya S.
      • Custers I.M.
      • Coutifaris C.
      • Goverde A.J.
      • Guzick D.S.
      • Litvak P.F.
      • Steures P.N.
      • van der Veen F.
      • Bossuyt P.
      • Mol B.W.
      The prognostic profile of subfertile couples and treatment outcome after expectant management, intrauterine insemination and in vitro fertilisation: a study protocol for the meta-analysis of individual patient data.
      NR (Study project)
      • Matorras R.
      • Osuna C.
      • Exposito A.
      • Crisol L.
      • Pijoan J.I.
      Recombinant FSH versus highly purified FSH in intrauterine insemination: systematic review and metaanalysis.
      1581PartnerMultiple pregnancy; OHSSNR0
      • Van der Poel N.
      • Farquhar C.
      • Abou-Setta A.M.
      • Benschop L.
      • Heineman M.J.
      Soft versus firm catheters for intrauterine insemination.
      1,350PartnerMiscarriages; multiple pregnancy; endometrial or cervical traumaNR0
      • Polyzos N.P.
      • Tzioras S.
      • Mauri D.
      • Tatsioni A.
      Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials.
      1,018PartnerMiscarriagesNR0
      • Van Rumste M.M.
      • Custers I.M.
      • van der Veen F.
      • van Wely M.
      • Evers J.L.
      • Mol B.W.
      The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis.
      11,599BothMultiple pregnancyNR0
      • Kosmas I.P.
      • Tatsioni A.
      • Kolibianakis E.M.
      • Verpoest W.
      • Tournaye H.
      • Van der Elst J.
      • Devroey P.
      Effects and clinical significance of GnRH antagonist administration for IUI timing in FSH superovulated cycles: a meta-analysis.
      1,069PartnerMultiple pregnancyNR0
      • Cantineau A.E.
      • Cohlen B.J.
      • Heineman M.J.
      Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility.
      6,350BothMultiple pregnancy; OHSS; multiple pregnancy; miscarriagesNR0
      • Kosmas I.P.
      • Tatsioni A.
      • Fatemi H.M.
      • Kolibianakis E.M.
      • Tournaye H.
      • Devroey P.
      Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis.
      2,623BothNRNR0
      • Helmerhorst F.M.
      • van Vliet H.A.
      • Gornas T.
      • Finken M.J.
      • Grimes D.A.
      Intrauterine insemination versus timed intercourse for cervical hostility in subfertile couples.
      4,506PartnerMultiple pregnancy; OHSS; miscarriages; multiple pregnancyNR0
      • Abou-Setta A.M.
      • Mansour R.T.
      • Al-Inany H.G.
      • Aboulghar M.A.
      • Kamal A.
      • Aboulghar M.A.
      • Serour G.I.
      Intrauterine insemination catheters for assisted reproduction: a systematic review and meta-analysis.
      1,677NRMultiple pregnancyNR0
      • Osuna C.
      • Matorras R.
      • Pijoan J.I.
      • Rodríguez-Escudero F.J.
      One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature.
      1,156PartnerNRNR0
      • Costello M.F.
      Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination.
      911PartnerNRNR0
      Total43,960
      Final analysis included 43,048 cycles after exclusion of 5912 cycles which had been included in more than one meta-analysis.
      00
      OHSS, ovarian hyperstimulation syndrome.
      a Final analysis included 43,048 cycles after exclusion of 5912 cycles which had been included in more than one meta-analysis.
      Figure 1
      Figure 1Search of published meta-analyses. HIV, human immunodeficiency virus; IUI, intrauterine insemination.

      Review of prospective studies 2013–2014

      A PubMed search was carried out using the key words ‘IUI’ or ‘intrauterine insemination’. The search period was restricted to 2013–2014 (Table 3). Only randomized studies conducted on humans were considered. Studies not focusing on clinical outcomes were excluded. Eighteen studies were obtained. One of them (
      • Chaudhury K.
      • Chaudhury S.
      • Khastgir G.
      • Purakaystha S.
      An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial.
      ) was not included, as the original work could not be accessed, and the first author could not be contacted (Figure 2). No mention was found of antibiotic prophylaxis.
      Table 3Pelvic inflammatory disease rate analysis in the intrauterine insemination prospective randomized trials in the period 2013–2014.
      ArticleNumber of cyclesPartner/donorSpecific reference to complicationsNumber of infectionsPID rate (%)
      • Kaser D.J.
      • Goldman M.B.
      • Fung J.L.
      • Alper M.M.
      • Reindollar R.H.
      When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials.
      701PartnerMultiple pregnancyNR0
      • Karamahmutoglu H.
      • Erdem A.
      • Erdem M.
      • Mutlu M.F.
      • Bozkurt N.
      • Oktem M.
      • Ercan D.D.
      • Gumuslu S.
      The gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study.
      338PartnerNoNR
      • Goldman M.B.
      • Thornton K.L.
      • Ryley D.
      • Alper M.M.
      • Fung J.L.
      • Hornstein M.D.
      • Reindollar R.H.
      A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).
      178PartnerMultiple pregnancyNR0
      • Blockeel C.
      • Knez J.
      • Polyzos N.P.
      • De Vos M.
      • Camus M.
      • Tournaye H.
      Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.
      435DonorNoNR
      • Scholten I.
      • Moolenaar L.M.
      • Gianotten J.
      • van der Veen F.
      • Hompes P.G.
      • Mol B.W.
      • Steures P.
      Long term outcome in subfertile couples with isolated cervical factor.
      375PartnerEctopic pregnancy; multiple pregnancy; miscarriagesNR0
      • Farquhar C.M.
      • Brown J.
      • Arroll N.
      • Gupta D.
      • Boothroyd C.V.
      • Al Bassam M.
      • Moir J.
      • Johnson N.P.
      A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility.
      210BothEctopic pregnancy; multiple pregnancy; miscarriages; infections; OHSS00
      • Weiss A.
      • Beck-Fruchter R.
      • Lavee M.
      • Geslevich Y.
      • Golan J.
      • Ermoshkin A.
      • Shalev E.
      A randomized trial comparing time intervals from HCG trigger to intrauterine insemination for cycles utilizing GnRH antagonists.
      107BothOHSS; miscarriages; multiple pregnancyNR0
      • Chaudhury K.
      • Chaudhury S.
      • Khastgir G.
      • Purakaystha S.
      An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial.
      118
      A total of 4968 cycles were included in the analysis after exclusion of 118 cycles reported in Chaudhury et al. (2013), as the study could not be accessed.
      NA
      • Seckin B.
      • Turkcapar F.
      • Yildiz Y.
      • Senturk B.
      • Yilmaz N.
      • Gulerman C.
      Effect of luteal phase support with vaginal progesterone in intrauterine insemination cycles with regard to follicular response: a prospective randomized study.
      166NRMiscarriages; multiple pregnancy; multiple pregnancy; OHSSNR
      • Van Rumste M.M.
      • Custers I.M.
      • van Wely M.
      • Koks C.A.
      • van Weering H.G.
      • Beckers N.G.
      • Scheffer G.J.
      • Broekmans F.J.
      • Hompes P.G.
      • Mochtar M.H.
      • van der Veen F.
      • Mol B.W.
      IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.
      143PartnerOHSS; multiple pregnancyNR0
      • Romero Nieto M.I.
      • Lorente González J.
      • Arjona-Berral J.E.
      • Del Muñoz-Villanueva M.
      • Castelo-Branco C.
      Luteal phase support with progesterone in intrauterine insemination: a prospective randomized study.
      893BothMiscarriages; ectopic pregnancyNR0
      • Riad O.N.
      • Hak A.A.
      Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination.
      .
      90PartnerNoNR
      • Asadi M.
      • Matin N.
      • Frootan M.
      • Mohamadpour J.
      • Qorbani M.
      • Tanha F.D.
      Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.
      110NRNoNR
      • Aydin Y.
      • Hassa H.
      • Oge T.
      • Tokgoz V.Y.
      A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles.
      220PartnerNoNR
      • Oruç A.S.
      • Yılmaz N.
      • Görkem U.
      • Inal H.A.
      • Seçkin B.
      • Gülerman C.
      Influence of ultrasound-guided artificial insemination on pregnancy rates: a randomized study.
      387PartnerNoNR
      • Rashidi M.
      • Aaleyasin A.
      • Aghahosseini M.
      • Loloi S.
      • Kokab A.
      • Najmi Z.
      Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility.
      259PartnerMiscarriages; multiple pregnancy; OHSSNR0
      • Kamath M.S.
      • R R.
      • Bhave P.
      • K M.
      • T K A.
      • George K.
      Effectiveness of GnRH antagonist in intrauterine insemination cycles.
      236PartnerNoNR
      • Pourmatroud E.
      • Zargar M.
      • Nikbakht R.
      • Moramazi F.
      A new look at tamoxifen: co-administration with letrozole in intrauterine insemination cycles.
      120PartnerOHSS; miscarriages; ectopic pregnancyNR0
      Total5086
      A total of 4968 cycles were included in the analysis after exclusion of 118 cycles reported in Chaudhury et al. (2013), as the study could not be accessed.
      0
      OHSS, ovarian hyperstimulation syndrome; PID, pelvic inflammatory disease.
      a A total of 4968 cycles were included in the analysis after exclusion of 118 cycles reported in
      • Chaudhury K.
      • Chaudhury S.
      • Khastgir G.
      • Purakaystha S.
      An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial.
      , as the study could not be accessed.
      Figure 2
      Figure 2Search of published prospective randomized trials.

      Review of our centre's records

      We reviewed our centre's IUI complication register during 1993–2016, finding 12,720 IUI cycles (8398 with husband sperm and 4322 with donor sperm). Most cycles were stimulated with gonadotrophin, and only one insemination was carried out per cycle. All patients had tubal patency assessed by hysterosalpingography. Antibiotic prophylaxis was never administered. Women received six inseminations, unless pregnancy was achieved before. The definition of PID was presence of clinical symptoms requiring hospitalization and antibiotic therapy. Data corresponding to 2002–2013 were already included in the Spanish Fertility Society register.

      Results

      Analysis of retrospective registers

      The first register corresponded to 48,000 cycles from California Cryobank, resulting in a post-IUI PID rate of 0.17/1000 (8/48,000) (Table 1). Donor sperm were used in all these IUI.
      The Spanish Fertility Society register included 317,874 IUI cycles: 135,839 corresponded to husband sperm and 33,712 to donor sperm, and for the remaining cycles, in the latest years, no differentiation was made between donor and husband sperm.
      The combined analysis of the two registers resulted in a PID rate of 0.16/1000 cycles (57/365,874) (95% CI 0.2 to 0.3/1000). The frequency was 0.21/1000 (28/135,839) in cycles with the husband's sperm compared with 0.11/1000 in donor sperm cycles (9/81,712) (Yates chi squared = 2.23, non-significant). The relative risk was 1.87 (95% CI 0.88 to 3.97).
      Given that the technique has changed significantly over time, and that there was a remarkable heterogeneity in the period covered by the two registers (1986–2004 for the California and 2002–2013 for the Spanish one), a second analysis was conducted, which was restricted to the Spanish register for the period 2002–2008 (as data were not subsequently subdivided into donor and husband sperm cycles).
      The PID rate for husband sperm cycles was 0.21/1000 (28/135,839), which is significantly higher than the value of 0.03/1000 (1/33,712) in donor sperm cycles (Yates chi-squared = 3.94; P = 0.047). The relative risk was 6.95 (95% CI 0.95 to 51.06).

      Meta-analysis review

      Our search retrieved 19 meta-analyses (
      • Abou-Setta A.M.
      • Mansour R.T.
      • Al-Inany H.G.
      • Aboulghar M.A.
      • Kamal A.
      • Aboulghar M.A.
      • Serour G.I.
      Intrauterine insemination catheters for assisted reproduction: a systematic review and meta-analysis.
      ,
      • Cantineau A.E.
      • Cohlen B.J.
      • Heineman M.J.
      Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility.
      ,
      • Cantineau A.E.
      • Cohlen B.J.
      • Heineman M.J.
      • Marjoribanks J.
      • Farquhar C.
      Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility.
      ,
      • Cantineau A.E.
      • Janssen M.J.
      • Cohlen B.J.
      • Allersma T.
      Synchronised approach for intrauterine insemination in subfertile couples.
      ,
      • Costello M.F.
      Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination.
      ,
      • Helmerhorst F.M.
      • van Vliet H.A.
      • Gornas T.
      • Finken M.J.
      • Grimes D.A.
      Intrauterine insemination versus timed intercourse for cervical hostility in subfertile couples.
      ,
      • Hill M.J.
      • Whitcomb B.W.
      • Lewis T.D.
      • Wu M.
      • Terry N.
      • DeCherney A.H.
      • Levens E.D.
      • Propst A.M.
      Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis.
      ,
      • Kosmas I.P.
      • Tatsioni A.
      • Fatemi H.M.
      • Kolibianakis E.M.
      • Tournaye H.
      • Devroey P.
      Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis.
      ,
      • Kosmas I.P.
      • Tatsioni A.
      • Kolibianakis E.M.
      • Verpoest W.
      • Tournaye H.
      • Van der Elst J.
      • Devroey P.
      Effects and clinical significance of GnRH antagonist administration for IUI timing in FSH superovulated cycles: a meta-analysis.
      ,
      • Luo S.
      • Li S.
      • Jin S.
      • Li Y.
      • Zhang Y.
      Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.
      ,
      • Matorras R.
      • Osuna C.
      • Exposito A.
      • Crisol L.
      • Pijoan J.I.
      Recombinant FSH versus highly purified FSH in intrauterine insemination: systematic review and metaanalysis.
      ,
      • Miralpeix E.
      • González-Comadran M.
      • Solà I.
      • Manau D.
      • Carreras R.
      • Checa M.A.
      Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.
      ,
      • Osuna C.
      • Matorras R.
      • Pijoan J.I.
      • Rodríguez-Escudero F.J.
      One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature.
      ,
      • Polyzos N.P.
      • Tzioras S.
      • Mauri D.
      • Tatsioni A.
      Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials.
      ,
      • Van der Poel N.
      • Farquhar C.
      • Abou-Setta A.M.
      • Benschop L.
      • Heineman M.J.
      Soft versus firm catheters for intrauterine insemination.
      ,
      • Van Rumste M.M.
      • Custers I.M.
      • van der Veen F.
      • van Wely M.
      • Evers J.L.
      • Mol B.W.
      The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis.
      ,
      • Veltman-Verhulst S.M.
      • Cohlen B.J.
      • Hughes E.
      • Heineman M.J.
      Intra-uterine insemination for unexplained subfertility.
      ,
      • Zavos A.
      • Daponte A.
      • Garas A.
      • Verykouki C.
      • Papanikolaou E.
      • Anifandis G.
      • Polyzos N.P.
      Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis.
      ) (Table 2 and Supplementary Table S1), resulting initially in 48,960 IUI cycles. A total of 5912 cycles, however, had been included in more than one meta-analysis, so the final analysis was restricted to 43,048 cycles. None of them reported on PID. In four cycles, no reference was made to any kind of complication (
      • Costello M.F.
      Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination.
      ,
      • Kosmas I.P.
      • Tatsioni A.
      • Kolibianakis E.M.
      • Verpoest W.
      • Tournaye H.
      • Van der Elst J.
      • Devroey P.
      Effects and clinical significance of GnRH antagonist administration for IUI timing in FSH superovulated cycles: a meta-analysis.
      ,
      • Osuna C.
      • Matorras R.
      • Pijoan J.I.
      • Rodríguez-Escudero F.J.
      One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature.
      ,
      • Zavos A.
      • Daponte A.
      • Garas A.
      • Verykouki C.
      • Papanikolaou E.
      • Anifandis G.
      • Polyzos N.P.
      Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis.
      ). In the remaining 15, the complications described were multiple pregnancy, ectopic pregnancies, miscarriages and hyperstimulation syndrome. Therefore, the reported PID rate was 0/1000 (0/43,048) (95% CI 0 to 0.1/1000).

      Review of prospective studies published between 2013 and 2014

      For the period 2013–2014 (Table 3), we reviewed 17 reports (
      • Asadi M.
      • Matin N.
      • Frootan M.
      • Mohamadpour J.
      • Qorbani M.
      • Tanha F.D.
      Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.
      ,
      • Aydin Y.
      • Hassa H.
      • Oge T.
      • Tokgoz V.Y.
      A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles.
      ,
      • Blockeel C.
      • Knez J.
      • Polyzos N.P.
      • De Vos M.
      • Camus M.
      • Tournaye H.
      Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.
      ,
      • Farquhar C.M.
      • Brown J.
      • Arroll N.
      • Gupta D.
      • Boothroyd C.V.
      • Al Bassam M.
      • Moir J.
      • Johnson N.P.
      A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility.
      ,
      • Goldman M.B.
      • Thornton K.L.
      • Ryley D.
      • Alper M.M.
      • Fung J.L.
      • Hornstein M.D.
      • Reindollar R.H.
      A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).
      ,
      • Kamath M.S.
      • R R.
      • Bhave P.
      • K M.
      • T K A.
      • George K.
      Effectiveness of GnRH antagonist in intrauterine insemination cycles.
      ,
      • Karamahmutoglu H.
      • Erdem A.
      • Erdem M.
      • Mutlu M.F.
      • Bozkurt N.
      • Oktem M.
      • Ercan D.D.
      • Gumuslu S.
      The gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study.
      ,
      • Kaser D.J.
      • Goldman M.B.
      • Fung J.L.
      • Alper M.M.
      • Reindollar R.H.
      When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials.
      ,
      • Oruç A.S.
      • Yılmaz N.
      • Görkem U.
      • Inal H.A.
      • Seçkin B.
      • Gülerman C.
      Influence of ultrasound-guided artificial insemination on pregnancy rates: a randomized study.
      ,
      • Pourmatroud E.
      • Zargar M.
      • Nikbakht R.
      • Moramazi F.
      A new look at tamoxifen: co-administration with letrozole in intrauterine insemination cycles.
      ,
      • Rashidi M.
      • Aaleyasin A.
      • Aghahosseini M.
      • Loloi S.
      • Kokab A.
      • Najmi Z.
      Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility.
      ,
      • Riad O.N.
      • Hak A.A.
      Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination.
      ;
      • Romero Nieto M.I.
      • Lorente González J.
      • Arjona-Berral J.E.
      • Del Muñoz-Villanueva M.
      • Castelo-Branco C.
      Luteal phase support with progesterone in intrauterine insemination: a prospective randomized study.
      ,
      • Scholten I.
      • Moolenaar L.M.
      • Gianotten J.
      • van der Veen F.
      • Hompes P.G.
      • Mol B.W.
      • Steures P.
      Long term outcome in subfertile couples with isolated cervical factor.
      ,
      • Seckin B.
      • Turkcapar F.
      • Yildiz Y.
      • Senturk B.
      • Yilmaz N.
      • Gulerman C.
      Effect of luteal phase support with vaginal progesterone in intrauterine insemination cycles with regard to follicular response: a prospective randomized study.
      ,
      • Van Rumste M.M.
      • Custers I.M.
      • van Wely M.
      • Koks C.A.
      • van Weering H.G.
      • Beckers N.G.
      • Scheffer G.J.
      • Broekmans F.J.
      • Hompes P.G.
      • Mochtar M.H.
      • van der Veen F.
      • Mol B.W.
      IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.
      ;
      • Weiss A.
      • Beck-Fruchter R.
      • Lavee M.
      • Geslevich Y.
      • Golan J.
      • Ermoshkin A.
      • Shalev E.
      A randomized trial comparing time intervals from HCG trigger to intrauterine insemination for cycles utilizing GnRH antagonists.
      ) totalling 4968 cycles. In seven reports, no mention was made of complications (
      • Asadi M.
      • Matin N.
      • Frootan M.
      • Mohamadpour J.
      • Qorbani M.
      • Tanha F.D.
      Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.
      ,
      • Aydin Y.
      • Hassa H.
      • Oge T.
      • Tokgoz V.Y.
      A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles.
      ,
      • Blockeel C.
      • Knez J.
      • Polyzos N.P.
      • De Vos M.
      • Camus M.
      • Tournaye H.
      Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.
      ,
      • Kamath M.S.
      • R R.
      • Bhave P.
      • K M.
      • T K A.
      • George K.
      Effectiveness of GnRH antagonist in intrauterine insemination cycles.
      ,
      • Karamahmutoglu H.
      • Erdem A.
      • Erdem M.
      • Mutlu M.F.
      • Bozkurt N.
      • Oktem M.
      • Ercan D.D.
      • Gumuslu S.
      The gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study.
      ,
      • Oruç A.S.
      • Yılmaz N.
      • Görkem U.
      • Inal H.A.
      • Seçkin B.
      • Gülerman C.
      Influence of ultrasound-guided artificial insemination on pregnancy rates: a randomized study.
      ,
      • Riad O.N.
      • Hak A.A.
      Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination.
      ). Only in one (
      • Farquhar C.M.
      • Brown J.
      • Arroll N.
      • Gupta D.
      • Boothroyd C.V.
      • Al Bassam M.
      • Moir J.
      • Johnson N.P.
      A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility.
      ), was the infection rate specifically mentioned (‘There were no cases of post-procedural infection’). In the remaining reports, a number of complications were addressed (multiple pregnancy, miscarriages, ectopic pregnancy, hyperstimulation syndrome), but no mention was made of PID. Therefore, the reported PID rate was 0/1000 (0/4968) (95% CI 0 to 0.7/1000).

      Review of our center's records

      Two cases of PID after IUI were reported, representing 1.6/1000 (2/12,720) (95% CI 0 to 0.6/1000). Both these cases occurred in husband sperm cycles (2/8398 = 0.24/1000) (95% CI 0 to 0.9/1000) with no case with donor sperm (0/4322) (95% CI 0 to 0.9/1000).

      Discussion

      The most relevant pathogenic mechanism in PID is the ascending spread of microorganisms from the vagina and cervix into the upper genital tract. Hypothetically, IUI could promote PID as it sweeps along the microorganisms from the cervix. The introduction of the catheter could act as a foreign body in the uterine cavity, and the deposit of processed sperm in the uterine cavity could also cause PID. A similar mechanism has been proposed for PID cases after hysterosalpingography, endometrial biopsy, curettage or IUD insertion.
      In their textbook,
      • Speroff L.
      • Glass R.H.
      • Kase N.G.
      Male infertility.
      quote a frequency of 1/500 PID after IUI; however, other reported frequencies range from as high as 1/100 (
      • Sable D.B.
      • Yanushpolsky E.H.
      • Fox J.H.
      Ruptured pelvic abscess after intrauterine insemination: a case report.
      ) to 6.8/1000 (
      • Sacks P.C.
      • Simon J.A.
      Infectious Complications of Intrauterine Insemination: a case report and literature review.
      ). These reports, however, are based on relatively small populations and lack statistical power. Indeed, one cannot discount publication bias, as a study on complication rates, in which a relatively high complication rate is found, has more chances of being published than those not reporting any complications at all.
      Hence, it is important that reviews analyse a large number of cases. Moreover, we estimated frequency using three different methods: analysis of two state/national retrospective registers; analysis of 19 prospective meta-analyses; and analysis of 17 individual prospective reports. Finally, we compared the obtained frequency with our centre's data.
      From our ‘state register’ analysis, with more than 350,000 IUI cycles, the PID rate was 1.6/10,000, much lower than that usually reported. In this analysis, one cannot rule out an underreporting rate, as in all retrospective studies.
      In the present meta-analysis, the PID rate was expected to be reported, as all important harms or unintended effects in each group should be reported (
      • Schulz K.F.
      • Altman D.G.
      • Moher D.
      CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials.
      ); however, no case of PID was reported in over 40,000 cycles. We cannot, however, rule out that PID occurred after IUI in some studies but was not reported as it did not pertain to the aim of the study. The resulting reported PID rate was 0/10,000, slightly lower than that obtained in our state register analysis. When we conducted a similar study on all the prospective single reports on IUI during a 2-year period, again, no case was reported. Therefore, we cannot rule out underreporting for these reasons. In any case, the upper limit of the confidence interval in both analyses was not too far from the confidence intervals from our register study.
      Finally, from our own centre's IUI register, we obtained a PID rate of 1.6/10,000, exactly the same rate that we reported in the ‘retrospective register’ analysis. We also observed a non-significant trend to higher PID rates in husband sperm cycles.
      In a recent US nationally representative population of sexually experienced women of reproductive age, the reported prevalence of women with a history of PID increased from 2.9% among women aged 18–24 years to 6.7% among women aged 40–44 years (
      • Kreisel K.
      • Torrone E.
      • Bernstein K.
      • Hong J.
      • Gorwitz R.
      Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age – United States, 2013–2014.
      ). Therefore, in the general population, the expected per month rate should be that difference (3.8%) divided by 338 (13 cycles per year multiplied by 26 years, the difference between the maximum and the minimum age). The resulting per month PID rate would be 1.12/10,000, which does not differ significantly from the value of 1.6/10,000 from our register population (44/395,798 (
      • Kreisel K.
      • Torrone E.
      • Bernstein K.
      • Hong J.
      • Gorwitz R.
      Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age – United States, 2013–2014.
      ) versus 57/365,874; relative risk 1,40; 95% C 0.95 to 2.07). The general population studied by
      • Kreisel K.
      • Torrone E.
      • Bernstein K.
      • Hong J.
      • Gorwitz R.
      Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age – United States, 2013–2014.
      and the population of infertile women in the present study differ remarkably. Infertile women probably have more undiagnosed tubal conditions, less current use of barrier contraceptive methods and a lower number of current partners. In comparing both figures, it could be stated that PID after IUI is roughly 40% higher than in a normal cycle in the unselected population. Our report does not address subclinical PID, of which the repercussions are difficult to quantify. Subclinical PID was not addressed in the WWM report (
      • Kreisel K.
      • Torrone E.
      • Bernstein K.
      • Hong J.
      • Gorwitz R.
      Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age – United States, 2013–2014.
      ).
      In the register analysis, when the sperm source was considered, a non-significant trend to higher PID rates was observed in husband sperm insemination (2/10,000) than in donor insemination (1.1/10,000). Between 1986 and 2001, all the cases corresponded to donor cycles, demonstrating remarkable chronologic heterogeneity. Therefore, when the analysis was restricted to the period 2002–2008 (the only time period were the exact number of donor and husband sperm cycles could be ascertained), the PID rate in husband sperm cycles (2/10,000) was significantly higher than in donor sperm cycles (0.3/10,000), with a relative risk of 6.95 (95% CI 0.95 to 51.06). It was not, however, possible to ascertain from our analysis whether this was caused by a reduced risk linked with donor sperm (microbiological screening of donors or perhaps due to the freezing procedure) or with a different profile among women undergoing husband or donor sperm insemination. We could speculate that women undergoing husband sperm insemination could have a higher proportion of mild tubal factor, that could facilitate PID. Indeed, a number of women receiving donor sperm are either single or lesbians and perhaps have a different cervicovaginal microbiological status. In this context, it has been reported that sexually transmitted diseases are transmitted more efficiently during heterosexual intercourse, than during lesbian intercourse (
      • Marrazzo J.M.
      • Coffey P.
      • Bingham A.
      Sexual practices, risk perception and knowledge of sexually transmitted disease risk among lesbian and bisexual women.
      ). This could also be attributed to a reporting bias by a commercial cryobank.
      In conclusion, on the basis of our analysis, the reported PID rate after IUI is low, close to 1.6/10,000 cycles, roughly 40% higher than in one ovarian cycle in the unselected population. Prophylactic antibiotic therapy is not recommended, unless there is a pre-existing risk factor.

      Appendix. Supplementary material

      The following is the supplementary data to this article:

      References

        • Abou-Setta A.M.
        • Mansour R.T.
        • Al-Inany H.G.
        • Aboulghar M.A.
        • Kamal A.
        • Aboulghar M.A.
        • Serour G.I.
        Intrauterine insemination catheters for assisted reproduction: a systematic review and meta-analysis.
        Hum. Reprod. 2006; 21: 1961-1967
        • Asadi M.
        • Matin N.
        • Frootan M.
        • Mohamadpour J.
        • Qorbani M.
        • Tanha F.D.
        Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.
        Arch. Gynecol. Obstet. 2014; 289: 865-870
        • Aydin Y.
        • Hassa H.
        • Oge T.
        • Tokgoz V.Y.
        A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 170: 444-448
        • Blockeel C.
        • Knez J.
        • Polyzos N.P.
        • De Vos M.
        • Camus M.
        • Tournaye H.
        Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.
        Hum. Reprod. 2014; 29: 697-703
        • Broder S.
        • Sims C.
        • Rothman C.
        Frequency of postinsemination infections as reported by donor semen recipients.
        Fertil. Steril. 2007; 88: 711-713
        • Cantineau A.E.
        • Cohlen B.J.
        • Heineman M.J.
        Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility.
        Cochrane Database Syst. Rev. 2007; (CD005356)
        • Cantineau A.E.
        • Cohlen B.J.
        • Heineman M.J.
        • Marjoribanks J.
        • Farquhar C.
        Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility.
        Cochrane Database Syst. Rev. 2013; (CD001502)
        • Cantineau A.E.
        • Janssen M.J.
        • Cohlen B.J.
        • Allersma T.
        Synchronised approach for intrauterine insemination in subfertile couples.
        Cochrane Database Syst. Rev. 2014; (CD006942)
        • Chaudhury K.
        • Chaudhury S.
        • Khastgir G.
        • Purakaystha S.
        An effective alternative to only gonadotrophin for controlled ovarian stimulation in unexplained infertility patients undergoing intra-uterine insemination: a clinical trial.
        J. Indian Med. Assoc. 2013; 111: 589-594
        • Costello M.F.
        Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination.
        Aust. N. Z. J. Obstet. Gynaecol. 2004; 44: 93-102
        • Calhaz-Jorge C.
        • de Geyter C.
        • Kupka M.S.
        • de Mouzon J.
        • Erb K.
        • Mocanu E.
        • Motrenko T.
        • Scaravelli G.
        • Wyns C.
        • Goossens V.
        • European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE)
        Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE.
        Hum. Reprod. 2016; 31: 1638-1652
        • Farquhar C.M.
        • Brown J.
        • Arroll N.
        • Gupta D.
        • Boothroyd C.V.
        • Al Bassam M.
        • Moir J.
        • Johnson N.P.
        A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility.
        Hum. Reprod. 2013; 28: 2134-2139
        • Goldman M.B.
        • Thornton K.L.
        • Ryley D.
        • Alper M.M.
        • Fung J.L.
        • Hornstein M.D.
        • Reindollar R.H.
        A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).
        Fertil. Steril. 2014; 101: 1574-1581
        • Helmerhorst F.M.
        • van Vliet H.A.
        • Gornas T.
        • Finken M.J.
        • Grimes D.A.
        Intrauterine insemination versus timed intercourse for cervical hostility in subfertile couples.
        Obstet. Gynecol. Surv. 2006; 61: 402-414
        • Hill M.J.
        • Whitcomb B.W.
        • Lewis T.D.
        • Wu M.
        • Terry N.
        • DeCherney A.H.
        • Levens E.D.
        • Propst A.M.
        Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis.
        Fertil. Steril. 2013; 100: 1373-1380
        • Kamath M.S.
        • R R.
        • Bhave P.
        • K M.
        • T K A.
        • George K.
        Effectiveness of GnRH antagonist in intrauterine insemination cycles.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 166: 168-172
        • Karamahmutoglu H.
        • Erdem A.
        • Erdem M.
        • Mutlu M.F.
        • Bozkurt N.
        • Oktem M.
        • Ercan D.D.
        • Gumuslu S.
        The gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study.
        J. Assist. Reprod. Genet. 2014; 31: 1139-1145
        • Kaser D.J.
        • Goldman M.B.
        • Fung J.L.
        • Alper M.M.
        • Reindollar R.H.
        When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials.
        Fertil. Steril. 2014; 102: 1331-1337
        • Kolb B.A.
        • Mercer L.
        • Peters A.J.
        • Kazer R.
        Abscess following therapeutic insemination.
        Infect. Dis. Obstet. Gynecol. 1994; 1: 249-251
        • Kosmas I.P.
        • Tatsioni A.
        • Fatemi H.M.
        • Kolibianakis E.M.
        • Tournaye H.
        • Devroey P.
        Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis.
        Fertil. Steril. 2007; 87: 607-612
        • Kosmas I.P.
        • Tatsioni A.
        • Kolibianakis E.M.
        • Verpoest W.
        • Tournaye H.
        • Van der Elst J.
        • Devroey P.
        Effects and clinical significance of GnRH antagonist administration for IUI timing in FSH superovulated cycles: a meta-analysis.
        Fertil. Steril. 2008; 90: 367-372
        • Kreisel K.
        • Torrone E.
        • Bernstein K.
        • Hong J.
        • Gorwitz R.
        Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age – United States, 2013–2014.
        MMWR Morb. Mortal. Wkly Rep. 2017; 66: 80-83
        • Luo S.
        • Li S.
        • Jin S.
        • Li Y.
        • Zhang Y.
        Effectiveness of GnRH antagonist in the management of subfertile couples undergoing controlled ovarian stimulation and intrauterine insemination: a meta-analysis.
        PLoS ONE. 2014; 9: e109133
        • Luo S.
        • Li S.
        • Li X.
        • Bai Y.
        • Jin S.
        Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination cycles in women with polycystic ovary syndrome: a meta-analysis.
        Gynecol. Endocrinol. 2014; 30: 255-259
        • Marrazzo J.M.
        • Coffey P.
        • Bingham A.
        Sexual practices, risk perception and knowledge of sexually transmitted disease risk among lesbian and bisexual women.
        Perspect. Sex. Reprod. Health. 2005; 37: 6-12
        • Matorras R.
        • Osuna C.
        • Exposito A.
        • Crisol L.
        • Pijoan J.I.
        Recombinant FSH versus highly purified FSH in intrauterine insemination: systematic review and metaanalysis.
        Fertil. Steril. 2011; 95: 1937-1942
        • Miralpeix E.
        • González-Comadran M.
        • Solà I.
        • Manau D.
        • Carreras R.
        • Checa M.A.
        Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.
        J. Assist. Reprod. Genet. 2014; 31: 89-100
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • The PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        Ann. Intern. Med. 2009; 151: 264-269
        • Moradan S.
        A ruptured tubo-ovarian abscess after intrauterine insemination; a case report.
        Iran. J. Reprod. Med. 2009; 7: 41-43
        • Oruç A.S.
        • Yılmaz N.
        • Görkem U.
        • Inal H.A.
        • Seçkin B.
        • Gülerman C.
        Influence of ultrasound-guided artificial insemination on pregnancy rates: a randomized study.
        Arch. Gynecol. Obstet. 2014; 289: 207-212
        • Osuna C.
        • Matorras R.
        • Pijoan J.I.
        • Rodríguez-Escudero F.J.
        One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature.
        Fertil. Steril. 2004; 82: 17-24
        • Paavonen J.
        • Westrom L.
        • Eschenbach D.
        Pelvic inflammatory disease.
        in: Holmes K. Sparling P. Stamm W. Sexually Transmitted Diseases. fourth ed. McGraw-Hill, New York, NY2008: 783-809
        • Pereira N.
        • Hutchinson A.P.
        • Lekovich J.P.
        • Hobeika E.
        • Elias R.T.
        Antibiotic prophylaxis for gynecologic procedures prior to and during the utilization of assisted reproductive technologies: a systematic review.
        J. Pathog. 2016; 2016: 4698314https://doi.org/10.1155/2016/4698314
        • Polyzos N.P.
        • Tzioras S.
        • Mauri D.
        • Tatsioni A.
        Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials.
        Fertil. Steril. 2010; 94: 1261-1266
        • Pourmatroud E.
        • Zargar M.
        • Nikbakht R.
        • Moramazi F.
        A new look at tamoxifen: co-administration with letrozole in intrauterine insemination cycles.
        Arch. Gynecol. Obstet. 2013; 287: 383-387
        • Rashidi M.
        • Aaleyasin A.
        • Aghahosseini M.
        • Loloi S.
        • Kokab A.
        • Najmi Z.
        Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 169: 244-247
        • Riad O.N.
        • Hak A.A.
        Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination.
        Gynecol. Endocrinol. 2014; 30: 70-73
        • Rock J.A.
        • Jones H.W.
        Pelvic inflammatory disease.
        in: Te Linde's Operative Gynecology. ninth ed. Lippincot Williams and Wilkins, 2003: 675-689
        • Romero Nieto M.I.
        • Lorente González J.
        • Arjona-Berral J.E.
        • Del Muñoz-Villanueva M.
        • Castelo-Branco C.
        Luteal phase support with progesterone in intrauterine insemination: a prospective randomized study.
        Gynecol. Endocrinol. 2014; 30: 197-201
        • Sable D.B.
        • Yanushpolsky E.H.
        • Fox J.H.
        Ruptured pelvic abscess after intrauterine insemination: a case report.
        Fertil. Steril. 1993; 59: 679-680
        • Sacks P.C.
        • Simon J.A.
        Infectious Complications of Intrauterine Insemination: a case report and literature review.
        Int. J. Fertil. 1991; 36: 331-339
        • Scholten I.
        • Moolenaar L.M.
        • Gianotten J.
        • van der Veen F.
        • Hompes P.G.
        • Mol B.W.
        • Steures P.
        Long term outcome in subfertile couples with isolated cervical factor.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 170: 429-433
        • Schulz K.F.
        • Altman D.G.
        • Moher D.
        CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials.
        Ann. Intern. Med. 2010; 152 (for the; CONSORT Group): 726-732
        • Seckin B.
        • Turkcapar F.
        • Yildiz Y.
        • Senturk B.
        • Yilmaz N.
        • Gulerman C.
        Effect of luteal phase support with vaginal progesterone in intrauterine insemination cycles with regard to follicular response: a prospective randomized study.
        J. Reprod. Med. 2014; 59: 260-266
        • Spanish Fertility Society
        Sociedad Española de Fertilidad. Informes Registro Nacional de Actividad-Registro SEF.
        • Speroff L.
        • Glass R.H.
        • Kase N.G.
        Male infertility.
        in: Clinical Gynecologic Endocrinology and Infertility. sixth ed. Lippincott Williams and Wilkins, 1999: 1090
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • Olkin I.
        • Williamson G.D.
        • Rennie D.
        • Moher D.
        • Becker B.J.
        • Sipe T.A.
        • Thacker S.B.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
        • Terao M.
        • Koga K.
        • Fujimoto A.
        • Wada-Hiraike O.
        • Osunaga Y.
        • Yano T.
        • Kozuma S.
        Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease.
        J. Obstet. Gynaecol. Res. 2014; 40: 495-500
        • Van den Boogaard N.M.
        • Hompes P.G.
        • Barnhart K.
        • Bhattacharya S.
        • Custers I.M.
        • Coutifaris C.
        • Goverde A.J.
        • Guzick D.S.
        • Litvak P.F.
        • Steures P.N.
        • van der Veen F.
        • Bossuyt P.
        • Mol B.W.
        The prognostic profile of subfertile couples and treatment outcome after expectant management, intrauterine insemination and in vitro fertilisation: a study protocol for the meta-analysis of individual patient data.
        Br. J. Obstet. Gynaecol. 2012; 119: 953-957
        • Van der Poel N.
        • Farquhar C.
        • Abou-Setta A.M.
        • Benschop L.
        • Heineman M.J.
        Soft versus firm catheters for intrauterine insemination.
        Cochrane Database Syst. Rev. 2010; (CD006225)
        • Van Eyk N.
        • van Schalkwyk J.
        Infectious diseases committee. antibiotic prophylaxis in gynaecologic procedures.
        J. Obstet. Gynaecol. Can. 2012; 275: 382-391
        • Van Rumste M.M.
        • Custers I.M.
        • van der Veen F.
        • van Wely M.
        • Evers J.L.
        • Mol B.W.
        The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis.
        Hum. Reprod. Update. 2008; 14: 563-570
        • Van Rumste M.M.
        • Custers I.M.
        • van Wely M.
        • Koks C.A.
        • van Weering H.G.
        • Beckers N.G.
        • Scheffer G.J.
        • Broekmans F.J.
        • Hompes P.G.
        • Mochtar M.H.
        • van der Veen F.
        • Mol B.W.
        IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.
        Reprod. Biomed. Online. 2014; 28: 336-342
        • Veltman-Verhulst S.M.
        • Cohlen B.J.
        • Hughes E.
        • Heineman M.J.
        Intra-uterine insemination for unexplained subfertility.
        Cochrane Database Syst. Rev. 2012; (CD001838)
        • Weiss A.
        • Beck-Fruchter R.
        • Lavee M.
        • Geslevich Y.
        • Golan J.
        • Ermoshkin A.
        • Shalev E.
        A randomized trial comparing time intervals from HCG trigger to intrauterine insemination for cycles utilizing GnRH antagonists.
        Syst. Biol. Reprod. Med. 2015; 61: 44-49
        • Weledji E.P.
        • Elong F.
        Small bowel obstruction and perforation attributed to tubo-ovarian abscess following ‘D’ and ‘C’.
        World J. Emerg. Surg. 2013; 8: 41
        • Zavos A.
        • Daponte A.
        • Garas A.
        • Verykouki C.
        • Papanikolaou E.
        • Anifandis G.
        • Polyzos N.P.
        Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis.
        Asian J. Androl. 2013; 15: 533-538

      Biography

      Roberto Matorras, M.D. is Professor and Head of Human Reproduction Unit at the Department of Obstetrics and Gynecology of Cruces Hospital, Vizcaya, Spain. He is involved with several societies, has arranged national and international conferences and has authored numerous books and publications.
      Key message
      The frequency of pelvic inflammatory disease after intrauterine insemination is low. Prophylactic antibiotic therapy is not recommended, unless the patient has a pre-existing risk factor.