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Intra‐uterine insemination for unexplained subfertility

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References

References to studies included in this review

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Agarwal 2004 {published and unpublished data}

Agarwal S, Mittal S. A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene. Indian Journal of Medical Research 2004;120(6):519‐22.

Arcaini 1996 {published data only}

Arcaini L, Bianchi S, Baglioni A, Marchini M, Tozzi L, Fedele L. Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study. Journal of Reproductive Medicine 1996;41(8):614‐8.

Arici 1994 {published and unpublished data}

Arici A, Byrd W, Bradshaw K, Kutteh WH, Marshburn P, Carr BR. Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: A prospective, randomized, crossover study during intrauterine insemination cycles. Fertility and Sterility 1994;61(2):314‐8.

Bhattacharya 2008 {published data only}

Bhattacharya S,  Harrild K,  Mollison J,  Wordsworth S,  Tay C,  Harrold A,  et al. Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. BMJ 2008;7(337):a716.
Wordsworth SA, Buchanan JA, Mollison JA, Harrild KA, Robertson LA, Tay C, et al. Clomifene citrate and intrauterine insemination as first‐line treatments for unexplained infertility: Are they cost‐effective?. Human Reproduction 2011;26(2):369‐75.

Chung 1995 {published data only}

Chung CC, Fleming R, Jamieson ME, Yates RWS, Coutts JRT. Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility. Human Reproduction 1995;10:3139‐41.

Crosignani 1991 {published data only}

Crosignani PG, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: A preliminary report (Centre 13: Willemsen, Nijmegen). Human Reproduction 1991;6(7):953‐8.
Crosignani PG, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: A preliminary report (Centre 16: Pellicer, Valencia). Human Reproduction 1991;6(7):953‐8.
Crosignani PG, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: A preliminary report (Centre 19: Martinez, Amsterdam). Human Reproduction 1991;6(7):953‐8.
Crosignani PG, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: A preliminary report (data from centre 10: Hedon , Montpellier). Human Reproduction 1991;6(7):953‐8.

Deaton 1990 {published data only}

Deaton J, Gibson M, Blackmer K, Nakajima S, Badger G, Brumsted J. A randomized controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility on surgically corrected endometriosis. Fertility and Sterility 1990;54(6):1083‐8.

Goverde 2000 {published data only}

Goverde AJ, McDonnell J, Vermeiden JP, Schats R, Rutten FF, Schoemaker J. Intrauterine insemination or in‐vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost‐effectiveness analysis. Lancet 2000;355(9197):13‐8.

Guzick 1999 {published data only}

Guzick D, Carson S, Coutifaris C, Overstreet J, Factor‐Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. New England Journal of Medicine 1999;340(3):177‐83.

Janko 1998 {published data only}

Janko P, Hruzik P, Pruzinec J, Saliba H, Zidzik J. Induction of ovulation with or without intrauterine insemination in cases of unexplained sterility. Fertility and Sterility 1998;70(3):S442.

Karlstrom 1993 {published data only}

Karlstrom P, Bergh T, Lundkvist O. A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. Fertility and Sterility 1993;59(3):554‐9.

Melis 1995 {published and unpublished data}

Melis GB, Paoletti AM, Ajossa S, Guerriero S, Depau GF, Mais V. Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse. Fertility and Sterility 1995;64(6):1088‐93.

Murdoch 1991 {published and unpublished data}

Murdoch AP, Harris M, Mahroo M, Williams M, Dunlop W. Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility. British Journal of Obstetrics and Gynaecology 1991;98(11):1107‐11.

Steures 2006a {published data only}

Custers IM, Van Rumste MME, Van Der Steeg JW, Van Wely MA, Hompes PGA, Bossuyt P, et al. Long‐term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment. Human Reproduction 2012;27(2):444‐50.
Steures P,  Van der Steeg JW,  Hompes PG,  Habbema JD,  Eijkemans MJ,  Broekmans FJ,  et al. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Lancet 2006;368(9531):216‐2.

References to studies excluded from this review

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Aanesen 2014 {published data only}

Aanesen A, Westerbotn M. Prospective study of a Swedish infertile cohort 2005‐08: Population characteristics, treatments and pregnancy rates. Family Practice. 2014;31(3):290‐297.

Aboulghar 1993 {published data only}

Aboulghar MA, Mansour RT, Serour GI, Amin Y, Abbas AM, Salah IM. Ovarian superstimulation and intrauterine insemination for the treatment of unexplained infertility. Fertility and Sterility 1993;60(2):303‐6.

Barros Delgadillo 2008 {published data only}

Barros Delgadillo JC, Martinez Barrios E, Moreno Aburto C, Godines Enriquez MS, Manzur Navarrete F, Sanchez Solis V, et al. Intrauterine insemination versus programmed intercourse in cycles of controlled ovaric hyperstimulation. Ginecologia y Obstetricia de Mexico 2008;76(1):18‐31.

Barros‐Delgadillo 2010 {published data only}

Barros‐Delgadillo JC, Trejo‐Castaneda H, E‐Ormsby C, Gavino‐Gavino F. Differing response to GnRH antagonists in cycles of ovarian hyperstimulation plus intrauterine insemination. Ginecologia y Obstetricia de Mexico 2010;78(1):15‐28.

Check 2013 {published data only}

Check JH, Liss J, Bollendorf A. Intrauterine insemination (IUI) does not improve pregnancy rates in infertile couples where semen parameters are normal and postcoital tests are adequate. Clinical and Experimental Obstetrics and Gynecology 2013;40(1):33‐34.

Doyle 1991 {published data only}

Doyle M, DeCherney A. The value of empiric intrauterine insemination (IUI) with superovulation: a prospective‐ randomised clinical trial. Fertility and Sterility 1991;56:S34.

Evans 1991 {published data only}

Evans J, Wells C, Gregory L, Walker S. A comparison of intrauterine insemination‐ intraperitoneal insemination and natural intercourse in superovulated women. Fertility and Sterility 1991;56(6):1183‐7.

Gregoriou 1995 {published data only}

Gregoriou O, Vitoratos N, Papadias C, Konidaris S, Gargaropoulos A, Louridas C. Controlled ovarian hyperstimulation with or without intrauterine insemination for the treatment of unexplained infertility. International Journal of Gynaecology and Obstetrics 1995;48:55‐9.

Ho 1998 {published data only}

Ho P, Yeung W, So W, Lau E. A randomised trial comparing the efficacy of ovarian stimulation and intrauterine insemination versus ovarian stimulation alone in the treatment of male infertility and unexplained infertility. British Journal of Obstetrics and Gynaecology 1998;105(suppl 17):43.

Kabouk 2010 {published data only}

Kabouk GB, Donadio NF, Dzik A, Freitas GC, Justen R, Cavagna M. A prospective randomized study comparing clomiphene citrate supplemented with recombinant FSH or low‐dose hCG in ovarian stimulation for intrauterine insemination. Fertility and sterility 2010;94 suppl 1(4):S160 Abstract no. P‐231.

Kirby 1991 {published data only}

Kirby C, Flaherty S, Godfrey B, Warnes G, Matthews C. A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse. Fertility and Sterility 1991;56(1):102‐7.

Leanza 2014a {published data only}

Leanza V, Coco L, Grasso F, Leanza G, Zarbo G, Palumbo M, et al. Ovulation induction with clomiphene citrate for infertile couple. Minerva Ginecologica 2014;66(3):309‐12.

Leanza 2014b {published data only}

Leanza V, Coco L, Grasso F, Leanza G, Zarbo G, Palumbo M, et al. Unexplained infertility and ovulatory induction with menopausal gonadotropins. Minerva Ginecologica 2014;66(3):303‐7.

Martinez 1990 {published data only}

Martinez AR, Bernardus RE, Voorhorst FJ, Vermeiden JP, Schoemaker J. Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study. Fertility and Sterility 1990;53(5):847‐53.

Martinez 1991 {published data only}

Martinez AR, Bernardus RE, Voorhorst FJ, Vermeiden JP, Schoemaker J. Pregnancy rates after timed intercourse or intrauterine insemination after human menopausal gonadotropin stimulation of normal ovulatory cycles: a controlled study. Fertility and Sterility 1991;55(2):258‐65.

Nulsen 1990 {published data only}

Randomized prospective trial of pergonal (HMG) superovulation with intrauterine insemination (IUI) versus IUI alone. Nulsen JC, Dumez S, Metzger DA. Fertility and Sterility 1990;54:S57.

Nulsen 1993 {published data only (unpublished sought but not used)}

Nulsen JC, Walsh S, Dumez S, Metzger DA. A randomized and longitudinal study of human menopausal gonadotropin with intrauterine insemination in the treatment of infertility. Obstetrics and Gynecology 1993;82(5):780‐6.

Peeraer 2013 {published data only}

Peeraer KA, Debrock S, De Loecker P, Laenen A, Welkenhuyzen M, Spiessens C, et al. Effect of controlled ovarian stimulation with low dose human menopausal gonadotrophin or clomiphene on reproductive outcome after intrauterine insemination: a prospective, multicenter randomized trial. Human Reproduction 2013;28 suppl 1:i71‐i73 O‐172.

Prentice 1995 {published data only}

Prentice A, Sacks GP, Morton NC, Deary AJ, Smith SK. Controlled ovarian stimulation (superovulation) and intrauterine insemination for the treatment of unexplained and minor male factor infertility. Human Reproduction 1995;10:112.

Serhal 1988 {published data only (unpublished sought but not used)}

Serhal PF, Katz M, Little V, Woronowski H. Unexplained infertility ‐ the value of Pergonal superovulation combined with intrauterine insemination. Fertility and Sterility 1988;49(4):602‐6.

Tummon 1997 {published data only}

Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertility and Sterility 1997;68(1):8‐12.

Wadhwa 2013 {published data only}

Wadhwa LA, Khanna RA, Gupta TA, Gupta SA, Arora SA, Nandwani S. Evaluation of role of GnRH antagonist in intrauterine insemination (IUI) cycles with mild ovarian hyperstimulation (MOH). Fertility and Sterility 2013;100 Suppl(3):S17‐S18.

Xu 2014 {published data only}

Xu BF, Wang GY, Fan WM, Chen Q, Zhang AJ. Which is the best protocol of ovarian stimulation prior to artificial insemination by donor. Journal of Reproduction and Contraception 2014;25(1):41‐8.

Zikopoulos 1993 {published data only}

Zikopoulos K, West C, Thong P, Kacser E, Morrison J, Wu F. Homologous intra‐uterine insemination has no advantage over timed natural intercourse when used in combination with ovulation induction for the treatment of unexplained infertility. Human Reproduction 1993;8(4):563‐7.

Aboulghar 2003

Aboulghar MA, Mansour RT, Serour GI, Al‐Inany HG. Diagnosis and management of unexplained infertility: an update. Archives of Gynecology and Obstetrics 2003;267(4):177‐88.

Balasch 2004

Balasch J. Gonadotrophin ovarian stimulation and intrauterine insemination for unexplained infertility. Reproductive Biomedicine online 2004;9(6):664‐72.

Bensdorp 2015

Bensdorp AJ, Tjon‐Kon‐Fat RI, Bossuyt PM, Koks CA, Oosterhuis GJ, Hoek A, et al. Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation. BMJ 2015;9(350):g7771.

Besselink 2008

Besselink DE, Farquhar C, Kremer JAM, Marjoribanks J, O'Brien PA. Cervical insemination versus intra‐uterine insemination of donor sperm for subfertility. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD000317.pub3]

Cantineau 2007

Cantineau AE, Cohlen BJ. Ovarian stimulation protocols (anti‐oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD005356.pub2]

Cohlen 1998

Cohlen BJ, te Velde ER, Looman CW, Eijckemans R, Habbema JD. Crossover or parallel design in infertility trials? The discussion continues. Fertility and Sterility 1998;70(1):40‐5.

Cohlen 2005

Cohlen B, Cantineau A, D'Hooghe T, Te Velde E. Multiple pregnancy after assisted reproduction. Lancet 2005;366(9484):452‐3.

Costello 2004

Costello MF. Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. Australian and New Zealand Journal of Obstetrics and Gynaecology 2004;44(2):93‐102.

Daya 1993

Daya S. Is there place for the crossover design in infertility trials?. Fertility and Sterility 1993;59(1):6‐7.

Daya 2003

Daya S. Pitfalls in the design and analysis of efficacy trials in subfertility. Human Reproduction 2003;18(5):1005‐9.

Deeks 2011

Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Dias 2008

Dias S, McNamee R, Vail A. Bias in frequently reported analyses of subfertility trials. Statistics in Medicine 2008;27(27):5605‐19.

Dickey 2005

Dickey RP. Risk factors for high‐order multiple pregnancy and multiple birth after controlled ovarian hyperstimulation: results of 4,062 intrauterine insemination cycles. Fertility and Sterility 2005;83(3):671‐83.

ESHRE 2006

Andersen AN, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE. Human Reproduction 2006;21(7):1680‐97.

Fauser 2005

Fauser BC, Devroey P, Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 2005;365(9473):1807‐16.

Gleicher 2000

Gleicher N, Oleske DM, Tur‐Kaspa I, Vidali A, Karande V. Reducing the risk of high‐order multiple pregnancy after ovarian stimulation with gonadotropins. New England Journal of Medicine 2000;343(1):2‐7.

Goverde 2005

Goverde AJ, Lambalk CB, McDonnell J, Schats R, Homburg R, Vermeiden JP. Further considerations on natural or mild hyperstimulation cycles for intrauterine insemination treatment: effects on pregnancy and multiple pregnancy rates. Human Reproduction 2005;20(11):3141‐6.

GRADEpro GDT 2015 [Computer program]

McMaster University (developed by Evidence Prime, Inc) available from www.gradepro.org. GRADEpro Guideline Development Tool. McMaster University (developed by Evidence Prime, Inc) available from www.gradepro.org, 2015.

Guzick 1998

Guzick DS, Sullivan MW, Adamson GD, Cedars MI, Falk RJ, Peterson EP, et al. Efficacy of treatment for unexplained infertility. Fertility and Sterility 1998;70(2):207‐13.

Healy 2004

Healy D. Damaged babies from assisted reproductive technologies: focus on the BESST (birth emphasizing a successful singleton at term) outcome. Fertility and Sterility 2004;81(3):512‐3.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60.

Higgins 2011

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Hughes 1997

Hughes EG. The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta‐analysis. Human Reproduction 1997;12(9):1865‐72.

Hughes 2003

Hughes EG. Stimulated intra‐uterine insemination is not a natural choice for the treatment of unexplained subfertility.'Effective treatment' or 'not a natural choice'?. Human Reproduction 2003;18(5):912‐14.

Johnson 2003

Johnson NP, Proctor M, Farquhar CM. Gaps in the evidence for fertility treatment ‐ an analysis of the Cochrane Menstrual Disorders and Subfertility Group database. Human Reproduction 2003;18(5):947‐54.

Kerin 1984

Kerin JFP, Peek J, Warnes GM, Kirby C, Jeffrey R, Matthews CD. Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen. Lancet 1984;1(8376):533‐5.

Khan 1996

Khan KS, Daya S, Collins JA, Walter SD. Empirical evidence of bias in infertility research: overestimation of treatment effect in crossover trials using pregnancy as the outcome measure. Fertility and Sterility 1996;65(5):939‐45.

Land 2003

Land JA, Evers JL. Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting. Human Reproduction 2003;18(2):455‐7.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Liberati 2009

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta‐analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine 2009;6:e1000100.

McDonnell 2004

McDonnell J, Goverde AJ, Vermeiden JP. The place of the crossover design in infertility trials: a maximum likelihood approach. Human Reproduction 2004;19(11):2537‐44.

Min 2004

Min JK, Breheny SA, MacLachlan V, Healy DL. What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction. Human Reproduction 2004;19(1):3‐7.

Nan 1994

Nan PM, Cohlen BJ, Te Velde ER, Van Kooij RJ, Eimers J, Van Zonneveld O, Habbema JDF. Intra‐uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study. Human Reproduction 1994;9(11):2022‐6.

NICE 2013

NICE (National Institute for Health and Care Excellence). Assessment and treatment for people with fertility problems. NICE clinical guidanceFebruary 2013, issue 156:5. [guidance.nice.org.uk/cg156]

Norman 2000

Norman GR, Daya S. The alternating‐sequence design (or multiple‐period crossover) trial for evaluating treatment efficacy in infertility. Fertility and Sterility 2000;74(2):319‐24.

Ombelet 2005

Ombelet W, De Sutter P, Van der Elst J, Martens G. Multiple gestation and infertility treatment: registration, reflection and reaction ‐ the Belgian project. Human Reproduction Update 2005;11(1):3‐14.

Ragni 2006

Ragni G, Caliari I, Nicolosi AE, Arnoldi M, Somigliana E, Crosignani PG. Preventing high‐order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 years' experience using low‐dose recombinant follicle‐stimulating hormone and gonadotropin‐releasing hormone antagonists. Fertility and Sterility 2006;85(3):619‐24.

RCOG 1998

RCOG. The management of infertility in secondary care ‐ evidence based guidelines No. 3. RCOG Press, London. London.

Ripps 1994

Ripps BA, Minhas BS, Carson SA, Buster JE. Intrauterine insemination in fertile women delivers larger numbers of sperm to the peritoneal fluid than intracervical insemination. Fertility and Sterility 1994;61(2):398‐400.

Rumste 2006

Van Rumste MM, Den Hartog JE, Dumoulin JC, Evers JL, Land JA. Is controlled ovarian stimulation in intrauterine insemination an acceptable therapy in couples with unexplained non‐conception in the perspective of multiple pregnancies?. Human reproduction 2006;21(3):701‐4.

Ryan 2004

Ryan GL, Zhang SH, Dokras A, Syrop CH, Van Voorhis BJ. The desire of infertile patients for multiple births. Fertility and Sterility 2004;81(3):500‐4.

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Snick 2008

Snick HK,  Collins JA,  Evers JL. What is the most valid comparison treatment in trials of intrauterine insemination, timed or uninfluenced intercourse? A systematic review and meta‐analysis of indirect evidence. Human Reproduction 2008;23(10):2239‐45.

Sterne 2011

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Steures 2006b

Steures P, Van der Steeg JW, Hompes PG, Van der Veen F, Mol BW. Results of intrauterine insemination in the Netherlands [Resultaten van intra‐uteriene inseminatie in Nederland]. Nederlands Tijdschrift der Geneeskunde 2006;150(20):1127‐33.

Stewart 2003

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Te Velde 1999

Te Velde ER, Cohlen BJ. The management of infertility. New England Journal of Medicine 1999;340(3):224‐6.

Tur 2005

Tur R, Barri PN, Coroleu B, Buxaderas R, Parera N, Balasch J. Use of a prediction model for high‐order multiple implantation after ovarian stimulation with gonadotropins. Fertility and Sterility 2005;83(1):116‐21.

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Vail A, Gardener E. Common statistical errors in the design and analysis of subfertility trials. Human Reproduction 2003;18(5):1000‐4.

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Zeyneloglu HB, Arici A, Olive DL, Duleba AJ. Comparison of intrauterine insemination with timed intercourse in superovulated cycles with gonadotropins: a meta‐analysis. Fertility and Sterility 1998;69(3):486‐91.

References to other published versions of this review

Jump to:

Veltman‐Verhulst 2012

Veltman‐Verhulst SM, Cohlen BJ, Hughes E, Heineman MJ. Intra‐uterine insemination for unexplained subfertility. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD001838.pub4]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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Agarwal 2004

Methods

Trial design: parallel
Single centre
Randomisation: random number table
Allocation concealment: sealed opaque envelopes

Nr of Pt randomised: IUI + OH 70; TI + OH 70
Nr of withdrawals: IUI + OH 26 (37%); TI + OH 1
(total 19%)

Participants

Couples with unexplained subfertility
Age: IUI + OH 29.52 years (± 3.65); TI + OH 28.83 years (± 4.76)
Duration of subfertility: IUI + OH 4.91 years (± 2.72); TI + OH 4.93 years (± 3.27)
Basic fertility work up normal, semen normal according to WHO 1987
Previous treatment: no

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: 50 mg to 150 mg CC/day, day 3 to day 7
Ovulation: 10,000 IU hCG when not more than 4 follicles of > 16 mm were present
Timing of IUI and TI: 36 hr to 40 hr after HCG
Duration of treatment: 6 cycles max

Outcomes

Live birth and PR per couple and per cycle
Miscarriage rate
Ectopic PR
Multiple pregnancies

Pregnancy confirmed by USS showing gestational sac

Notes

ITT analysis: possible
Author provided additional information
Unbalanced groups: dropouts 37% in IUI group, 1% in TI group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table

Allocation concealment (selection bias)

Low risk

Adequate; sealed opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

High risk

There was an unequal dropout in the treatment group due to financial reasons.

Selective reporting (reporting bias)

Unclear risk

Reported on live birth, however authors provided additional information on ongoing pregnancies and twin pregnancies resulting in different data used for meta‐analysis

Other bias

Low risk

Baseline demographic characteristics similar between the two groups
Arcaini 1996

Methods

Trial design: parallel
Single centre
Randomisation: method unclear
Allocation concealment: unclear

Nr of Pt randomised: IUI + OH 36; TI + OH 32
Nr of withdrawals: 14 (20.6%)

Participants

Couples with unexplained subfertility
Age: IUI + OH 34.6 years (± 4.9); TI + OH 33.4 years (± 4.7)
Duration of subfertility: IUI + OH 4.2 years (± 1.6); TI + OH 3.9 years (± 2.3)
Basic fertility work up normal, semen normal, not further specified
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: 100 mg CC/day, day 3 to day 7 and 1 to 3 ampoule hMG/day
Ovulation: 10,000 IU hCG when 2 to 6 follicles of > 17 mm were present
Timing IUI or TI: 24 hr and 48 hr after hCG
Duration of treatment: 5 cycles max

Outcomes

PR per couple
Miscarriage rate
Ectopic PR
Multiple pregnancies
OHSS

Pregnancy confirmed by USS

Notes

ITT analysis: yes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated

Allocation concealment (selection bias)

Unclear risk

Unclear

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

A total of 16 cancelled treatment cycles is described and analysed according to intention to treat. People who dropped out are clearly stated in a table

Selective reporting (reporting bias)

Unclear risk

Did not report on live birth, however, did not intend to report on live birth

Other bias

Low risk

Nothing detected
Arici 1994

Methods

Trial design: crossover (after 1 cycle)
Single centre
Randomisation: computer‐generated random number table
Allocation concealment: computer system utilising locked files

Nr of Pt randomised: 26
Nr of withdrawals: not clear

Participants

Couples with unexplained subfertility and couples with male factor subfertility
Age: mean 33 yrs (range 24 yrs to 41 yrs)
Duration of subfertility: mean 3.5 yrs (range 1 yr to 15 yrs)
Unexplained subfertility: basic fertility work up normal, semen normal according to WHO 1987 criteria
Previous treatment: no

Interventions

Comparison: IUI + NC versus IUI + OH
Stimulation method: 50 mg CC/day, day 5 to day 9

Timing:
Natural cycle: urinary LH test, IUI on day of LH peak and the next day
Stimulated cycle: 10,000 IU hCG when at least 1 follicle of 18 mm was present; IUI 32 hr after hCG
No cancellation criteria were given
Duration of treatment: 4 cycles max

Outcomes

Live birth and PR per couple
PR per 1st cycle
PR per cycle
Miscarriage rate
Ectopic PR
Multiple pregnancies

Pregnancy confirmed by USS showing gestational sac

Notes

ITT analysis: yes
Author provided additional information
5 Pt with treated minimal endometriosis were included as unexplained subfertility

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Adequate; computer system utilising locked files

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Author gave additional information on dropout rates of the couples with unexplained subfertility. Of the 26 women with unexplained subfertility, dropout occurred after one treatment cycle. Post‐crossover data are not included in the meta‐analysis

Selective reporting (reporting bias)

Low risk

Live birth data were obtained from the author

Other bias

Unclear risk

No sufficient information reported on baseline demographic characteristics
Bhattacharya 2008

Methods

Trial design: parallel
Multi centre (four teaching hospitals, one general hospital, Scotland)
Randomisation: computer‐generated randomisation schedule
Allocation concealment: central telephone system

Nr of Pt randomised: 509 with unexplained subfertility only (total 580)
Nr of withdrawals: 4

Participants

Couples with unexplained subfertility, (mild male factor infertility and minimal endometriosis)
Age: TI + NC 32 years (± 3.4); TI + OH 32 years (± 3.5); IUI + NC 32 (± 3.7)
Duration of subfertility: minimum 2 years, median 30 months all groups
Basic fertility work up normal, semen normal according to WHO (sperm motility < 20% included)
Previous treatment: not stated

Interventions

Comparison: TI (expectant management) + NC versus TI + OH versus IUI + NC
Stimulation method: 50 mg CC/day (starting dose), day 2 to day 6
Ovulation: confirmed by progesterone measure in TI + OH group, and urinary LH surge in IUI + NC group
Timing of IUI and TI: IUI 20 hr to 30 hr after LH surge, timing intercourse advised on cycle day 12 to 18
Duration of treatment: 6 cycles max

Outcomes

Live birth and PR per couple
Miscarriage rate
Ectopic PR
Multiple pregnancies

Pregnancy confirmed by USS showing gestational sac and foetal heart beat

Notes

The author provided additional data on the couples with unexplained subfertility only

The baseline characteristics of the participants reported are from the group total. ITT analysis was therefore possible and performed

Author provided additional information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Sequence generated by independent statistician

Allocation concealment (selection bias)

Low risk

Adequate; central telephone randomisation system

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up and participants who received alternative treatment are presented in a flow‐chart.

Selective reporting (reporting bias)

Low risk

Live birth data and adverse events are published

Other bias

Low risk

Nothing detected
Chung 1995

Methods

Trial design: parallel
Single centre
Randomisation: blocked randomisation scheme
Allocation concealment: numbered sealed envelopes

Nr of Pt randomised: 100
Total dropouts: 12 (12%)

Participants

Couples with unexplained subfertility
Age: IUI + OH 31.8 years (± 3.1); TI + OH 32.1 years (± 4.0)
Duration of subfertility: IUI + OH 4.7 years (± 2.0); TI + OH 5.3 years (± 2.6)
Basic fertility work up normal and semen 15 million motile per ejaculate
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: FSH 150 IU/day and GnRH nasal spray from day 21 on
Ovulation: 5000 IU hCG when < 4 follicles > 16mm
hCG post‐ovulatory for luteal support
Timing TI: 24 hr + 48 hr after hCG
Timing IUI: 36 hr to 48 hr after hCG
Duration of treatment: 3 cycles max

Outcomes

PR per couple and per cycle
Total delivered
Multiple pregnancies
Ectopic
Miscarriage rate

Notes

ITT analysis: possible
IUI was not possible on Sundays

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Blocked randomisation scheme

Allocation concealment (selection bias)

Low risk

Adequate; numbered sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

8/50 withdrawn and 6 treatment cycles cancelled in TI group, 4/50 withdrawn and 11 treatment cycles cancelled in IUI group. Reason for cycle cancellation was excessive response. Reason for withdrawal was not stated

Selective reporting (reporting bias)

Low risk

Live birth data and complication numbers were reported.

Other bias

Low risk

Nothing detected
Crosignani 1991

Methods

Data from centre 10: Hedon, Montpellier, France

Trial design: crossover (after 1 cycle)
Multi centre (19 European fertility centres, 4 centres comparing IUI versus TI)
Randomisation: not clear
Allocation concealment: unclear

Nr of Pt randomised: unclear
Nr of Pt analysed: total 90 (centre 10; 18 participants)
Nr of withdrawals: unclear

Participants

Couples with unexplained subfertility
Age: < 38yrs
Duration of subfertility: > 3yrs
Basic fertility work up normal, semen normal according to WHO 1987
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: not stated
Ovulation: not described
Timing: not described
No cancellation criteria were given
Duration of treatment: 2 cycles max

Outcomes

PR per 1st cycle
PR per cycle

Notes

ITT analysis: not possible
Author replied; could not provide additional information
Multicentre ESHRE trial.
Only 4 infertility centres compared IUI with superovulation alone. These centres were included in the analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Each centre used own randomisation method. The per‐centre method could not be obtained

Allocation concealment (selection bias)

Unclear risk

Unclear; each centre used own treatment allocation method. The per‐centre method could not be obtained

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

High risk

Details on participant withdrawal or loss to follow‐up were not stated

Selective reporting (reporting bias)

Unclear risk

Live birth data were not reported

Other bias

Unclear risk

Insufficient information available to evaluate this risk domain
Deaton 1990

Methods

Trial design: crossover (after 4 cycles)
Single centre
Randomisation: unclear
Allocation concealment: unclear

Nr of Pt randomised: 67
Nr of Pt analysed: 51 total, unexplained: 24
Nr of withdrawals: 4 pre‐crossover (6%)

Participants

Couples with unexplained subfertility and couples with surgically treated endometriosis
Age: 33 years (± 4.0)
Duration of subfertility: 3.5 years (±1.7)
Basic fertility work up normal, semen normal according to WHO criteria 1987
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI + NC
Stimulation method: 50 mg CC/day, day 5 to day 9

Timing:
Natural cycle: urinary LH and BBT timed intercourse
Stimulated cycle: 10,000 IU hCG when lead follicle was estimated to be at least 18 mm. IUI 36 hr after hCG injection
No cancellation criteria were given
Duration of treatment: 8 cycles max

Outcomes

Ongoing pregnancy rate
Multiple pregnancies
Ectopic pregnancies
Miscarriage rate
OHSS

Pregnancy: not further defined

Notes

ITT analysis: not possible
Participants with unexplained subfertility and endometriosis were included in this study; three participants with moderate and no participants with severe endometriosis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Sequence generation not stated

Allocation concealment (selection bias)

Unclear risk

Unclear

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

16/67 participants excluded from analysis due to anovulation, poor semen quality or inability to follow the treatment protocol. Of the remaining 51 participants, 6 couples did not complete treatment because of illness or relocation. 4/51 dropped out before cross‐over

Selective reporting (reporting bias)

Unclear risk

Live birth rate was not reported

Other bias

Unclear risk

Insufficient information available to evaluate this risk domain
Goverde 2000

Methods

Trial design: parallel
Single centre
Randomisation: computer‐generated randomisation schedule
Allocation concealment: numbered, masked and sealed envelopes
A power calculation was performed

Nr of participants randomised: 120 (unexplained IUI + NC and IUI + TI), 258 total
Nr of withdrawals: unclear

Participants

Couples with unexplained subfertility and couples with male factor subfertility
Age: IUI + NC 31.6 years (± 3.7); IUI + OH 31.7 years (± 3.9)
Duration of subfertility: IUI + NC 3.9 years (± 1.7); IUI + OH 4.2 years (± 1.9)
Basic fertility work up normal, semen normal when > 20 million progressive motile in ejaculate
Previous treatment: not stated

Interventions

Comparison: IUI + NC versus IUI + OH (versus IVF)
Stimulation method: 75 IU FSH (starting dose) until 1 to 3 follicles of 18 mm were seen on USS
hCG was withheld if > 3 follicles of 18 mm or > 6 of 14 mm were present
Timing:
Stimulated cycle: 10,000 IU hCG, IUI 40 hr to 42 hr after hCG;
Natural cycle: IUI 20 hr to 30 hr after detection of urinary LH‐surge
Cycles were cancelled when > 3 follicles of 18 mm or > 6 follicles of 14 mm were present
Duration of treatment: 6 cycles max

Outcomes

Live birth per couple
OHSS

Notes

ITT analysis: yes

Some dropouts because of spontaneous pregnancy

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation schedule

Allocation concealment (selection bias)

Low risk

Adequate; numbered, masked and sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

7/120 withdrew before 1st treatment cycle. Details on dropout not separately available for unexplained subfertility. Some participants dropped out because of spontaneous pregnancy. It is not known whether these participants are included in the IUI unexplained subfertility group

Selective reporting (reporting bias)

Low risk

Live birth and complication data were reported

Other bias

Low risk

Nothing detected; baseline demographic characteristics similar between the two groups
Guzick 1999

Methods

Trial design: Parallel
Multi centre (10 clinical sites)
Randomisation: computer‐generated permuted block
Allocation concealment: locked computer files

Nr of Pt randomised: 932 (465 treated with IUI)
Nr of Pt with unexplained subfertility: 211
Nr of withdrawals: 72 total (15%)

Participants

Couples with unexplained subfertility and couples with stage I or II treated endometriosis or male factor subfertility
Age: IUI + NC 32 years (± 4) IUI + OH 32 years (± 4)
Duration of subfertility: IUI + NC 3.8 years (± 2.6); IUI + OH 3.5 years (± 2.2)
Basic fertility work up normal, semen normal (according to WHO 1992)
Previous treatment: no previous treatment. (Pt excluded if previous ART)

Interventions

Comparison: IUI + NC versus IUI + OH
Stimulation method: 150 IU FSH/day, day 3 to day 7
Ovulation: IUI + OH: 10,000 IU hCG when 2 follicles of > 18 mm were present
IUI + NC: urine LH testing
Timing: IUI + OH: 36 hr to 40 hr after hCG
IUI + NC: IUI the day after urinary LH surge

Cycles were cancelled if serum E2 concentration > 3000 pg/ml

Duration of treatment: 4 cycles max

Outcomes

Live birth per couple
PR per couple
Ectopic PR

Pregnancy defined by two positive HCG tests. This is biochemical pregnancy, therefore not included in analysis

Notes

ITT analysis: not possible
Author replied; provided additional information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Author could not guarantee whether or not participants were truly randomised

Allocation concealment (selection bias)

Unclear risk

Author could not guarantee whether or not participants were truly randomised

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawal rates of the total group were presented: 4/465 treatment‐related withdrawal, 27/465 not treatment‐related. Numbers for unexplained subfertility group are not known.

Selective reporting (reporting bias)

Low risk

Live birth and complication data were reported

Other bias

Low risk

Nothing detected
Janko 1998

Methods

Trial design: parallel
Single centre
Randomisation: not clear
Allocation concealment: unclear

Nr of Pt randomised: 72
Nr of withdrawals: not stated

Participants

Couples with unexplained subfertility
Age: not stated
Duration of subfertility: > 3 yrs
Basic fertility work up normal, semen normal not further specified
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: hMG (10 amp per cycle)
Ovulation: 10,000 IU hCG
Timing: not specified
No cancellation criteria were given.
Duration of treatment: 3 cycles max

Outcomes

PR per cycle

Pregnancy not further defined

Notes

ITT analysis: possible
Abstract only.
Data calculated.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated

Allocation concealment (selection bias)

Unclear risk

Unclear; not stated

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

High risk

Not available

Selective reporting (reporting bias)

High risk

In this abstract the reported outcome data are minimal

Other bias

Unclear risk

Insufficient information available to evaluate this risk domain
Karlstrom 1993

Methods

Trial design: parallel
Single centre
Randomisation: not clear
Allocation concealment: unclear

Nr of Pt randomised: not clear
Nr of Pt analysed: 79
Nr of withdrawals: not clear

Participants

Couples with unexplained subfertility and minimal or mild endometriosis
Age: 32 years (range 21 years to 38 years)
Duration of subfertility: 5 years (range 2 years to 14 years)
Basic fertility work up normal, semen normal according to WHO 1987
Previous treatment: no

Interventions

Comparison: IUI + OH versus TI + OH (vs DIPI + OH vs IUI and DIPI + OH)
Stimulation method 1: 150 IU hMG starting dose, till one follicle of at least 17 mm was present or the detection of a LH surge in serum or urine
Monitoring: USS and serum E2
Ovulation: 10,000 IU hCG
Timing: IUI 36 hr to 41 hr after hCG or 24 hr after detection of LH surge. TI the two following nights after hCG injection.

Stimulation method 2: 100 mg CC/day for 5 days

Monitoring + Ovulation: urinary LH timed
Timing: IUI 20 hr to 28 hr after LH surge, TI day of LH surge and day after

Cycles were cancelled according to serum E2 rise

Duration of treatment: 1 cycle max

Outcomes

PR per cycle
Ectopic PR
Pregnancy not further defined

Notes

ITT analysis: not possible
When ovulation occurred during the weekend, participants were transferred to TI group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated

Allocation concealment (selection bias)

Unclear risk

Not stated

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Four withdrawals in clomiphene group due to absent LH surge, 5 withdrawals in hMG group due to absent LH surge, fast oestrogen rise or personal reasons.

Selective reporting (reporting bias)

Unclear risk

Live birth data were not reported

Other bias

Unclear risk

Insufficient information was reported on demographic characteristics to make a conclusive judgement

Melis 1995

Methods

Trial design: parallel
Randomisation: computer‐generated random number list
Allocation concealment: numbered opaque sealed envelopes

Nr of Pt randomised: 108
Nr of Pt analysed: 103
Nr of withdrawals: 5 (4.6%)

Participants

Couples with unexplained subfertility and couples with mild male factor subfertility
Age: 33.1 years (± 5.2)
Duration of subfertility: 4.3 years (± 1.4)
Basic fertility work up normal, semen normal according to WHO 1987 criteria
Previous treatment: yes, all couples

Interventions

Comparison: IUI + OH versus TI + OH
Stimulation method: 3 amp FSH/day
Monitoring: USS and plasma E2
Ovulation: 10,000 IU hCG when at least 2 follicles of 16 mm were present
Timing: TI 12 hr after HCG, IUI 30 hr to 36 hr after HCG
Cycles cancelled when plasma E2 level > 1500 pg/ml

Duration of treatment: 3 cycles max

Outcomes

Live birth per couple
PR/couple
Miscarriage
Multiple pregnancies
OHSS

Pregnancy confirmed by USS showing foetal heart activity

Notes

ITT analysis: possible
Author provided additional information
All participants had had previous fertility treatment
Pt with minor abnormalities were excluded from the study

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number list

Allocation concealment (selection bias)

Low risk

Adequate; numbered opaque sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Exclusion numbers were published for the overall group.The author provided additional information: 1/52 (IUI + OH group) withdrew, 4/56 (TI + OH group) withdrew. Reasons for dropout were family problems, poor response or exaggerated response

Selective reporting (reporting bias)

Low risk

Live birth data and complication numbers were available for analysis

Other bias

Unclear risk

Insufficient information was reported to make a conclusive judgement on participant demographic characteristics

Murdoch 1991

Methods

Trial design: parallel
Randomisation: random number sequence
Allocation concealment: via sequentially numbered opaque sealed envelopes

Nr of Pt randomised: 39
IUI + NC 19; IUI + OH 20
Nr of withdrawals: 5 (13%)

Participants

Couples with unexplained subfertility
Age: IUI + NC 30.5 years (± 3.1); IUI + OH 30.1 years (± 2.9)
Duration of subfertility: IUI + NC 5.7 years (± 2.4); IUI + OH 5.1 years (± 1.9)
Basic fertility work up done, semen normal (according to WHO 1987)
Previous treatment: no

Interventions

Comparison: IUI + NC versus IUI + OH (vs GIFT)
Stimulation method: 75 IU hMG/day and 200 micro gram buserelin 4 times daily intranasal
Ovulation: 5000 IU hCG, when < 4 follicles of > 16mm were seen.
Timing: 30 hr to 36 hr after hCG
Natural cycle: IUI on alternate days until ovulation confirmed on USS
Cycles were cancelled if > 4 dominant follicles were present

Duration of treatment: 3 cycles max

Outcomes

PR per couple and per cycle
Live birth
Multiple pregnancies

Clinical pregnancy defined by USS showing foetal heart activity

Notes

ITT analysis: yes
Author provided additional information

One pregnancy between treatment cycles
Ten cycles were abandoned because no treatment available at the weekend

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number sequence

Allocation concealment (selection bias)

Low risk

Adequate; numbered opaque sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Drop‐out rate 3/19 (IUI + NC), and 2/20 (IUI + OH)

Selective reporting (reporting bias)

Low risk

Live birth data were provided

Other bias

Low risk

Nothing detected
Steures 2006a

Methods

Trial design: parallel
Multi centre: 26 fertility centres in the Netherlands
Randomisation: computer‐generated sequence in balanced blocks
Allocation concealment: via opaque sealed envelopes

Nr of Pt randomised: 253
IUI + OH 127; TI (expectant management) + NC 126
Nr of withdrawals: 3 (IUI + OH) and 2 (TI + NC), 2 still pregnant (TI + NC)

Participants

Couples with unexplained subfertility and an intermediate prognosis of conceiving within the next 12 months (Hunault 30% to 40%)

Age: IUI + OH 33 years (± 3.4); TI + NC 33 years (± 3.19)
Duration of subfertility: IUI + OH 2.0 years (± 0.5);TI + NC 1.91 years (± 0.5)
Basic fertility work up done, semen analysis according to WHO 1987, normal postcoital test
Previous treatment: not stated

Interventions

Comparison: IUI + OH versus TI (expectant management) + NC
Stimulation method: FSH 37 to 150 IU/day or 50 mg to 150 mg CC/day
Monitoring: USS
Ovulation: 5000 or 10,000 IU hCG
Timing: IUI 36 hr to 40 hr after hCG

Cycles were cancelled when > 3 follicles of 16 mm or > 5 follicles of 12 mm were present

Duration of treatment: 6 months

Outcomes

Live birth/couple
PR/couple
Miscarriage rate
Multiple pregnancies

Notes

ITT analysis: yes
Author provided additional information

Only couples with an intermediate prognosis of conceiving were included, this influences the possible treatment effect

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated sequence in balanced blocks

Allocation concealment (selection bias)

Low risk

Adequate; via opaque sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Blinding was not possible because of the nature of the interventions and non‐blinding was not likely to affect the outcomes of interest

Incomplete outcome data (attrition bias)
All outcomes

Low risk

IUI + OH group, 3 participants lost to follow up, TI + NC group, 2 lost to follow up, 2 still pregnant

Selective reporting (reporting bias)

Low risk

Live birth and complications reported

Other bias

Low risk

Nothing detected

CC: clomiphene citrate
DIPI: direct intraperitoneal insemination
FSH: follicle stimulating hormone
hCG: human chorionic gonadotropin
hMG: human menopausal gonadotropin
IUI: intra‐uterine insemination
OH: ovarian hyperstimulation
USS: ultrasound scan

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Aanesen 2014

Cohort study

Aboulghar 1993

The trial was not randomised

Barros Delgadillo 2008

Not RCT

Barros‐Delgadillo 2010

Did not include comparison of interest to this review

Check 2013

Not RCT

Doyle 1991

No pre‐crossover data available

Evans 1991

No pre‐crossover data available

Gregoriou 1995

No pre‐crossover data available

Ho 1998

Abstract, full article not available. No separate data for couples with unexplained subfertility

Kabouk 2010

Did not include comparison of interest to this review

Kirby 1991

No pre‐crossover data available

Leanza 2014a

Did not include comparison of interest to this review

Leanza 2014b

Did not include comparison of interest to this review

Martinez 1990

No per‐woman data. Biochemical pregnancies only reported

Martinez 1991

No pre‐crossover data available

Nulsen 1990

The trial (published as full paper in 1993) was not randomised

Nulsen 1993

The trial (also published as an abstract in 1990) was not randomised

Peeraer 2013

Did not include comparison of interest to this review

Prentice 1995

This trial was quasi randomised, on the basis of hospital case record number

Serhal 1988

The trial was not randomised

Tummon 1997

The participants in this trial were all diagnosed with endometriosis

Wadhwa 2013

Did not include comparison of interest to this review

Xu 2014

Study involved donor semen

Zikopoulos 1993

No pre‐crossover data available

Data and analyses

Open in table viewer
Comparison 1. IUI versus TI or expectant management both in natural cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [0.92, 2.78]
Analysis 1.1
Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

2 Multiple pregnancy rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.04, 5.53]
Analysis 1.2
Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

3 Pregnancy rate per couple (all cycles) Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

1.53 [0.88, 2.64]
Analysis 1.3
Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

4 Miscarriage rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

0.77 [0.28, 2.11]
Analysis 1.4
Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 4 Miscarriage rate per couple.

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 4 Miscarriage rate per couple.

5 Ectopic pregnancy rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

5.06 [0.24, 106.21]
Analysis 1.5
Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 5 Ectopic pregnancy rate per couple.

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 5 Ectopic pregnancy rate per couple.

Open in table viewer
Comparison 2. IUI versus TI or expectant management both in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.59 [0.88, 2.88]
Analysis 2.1
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

1.1 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.59 [0.88, 2.88]

2 Multiple pregnancy rate per couple Show forest plot

4

316

Odds Ratio (M‐H, Fixed, 95% CI)

1.46 [0.55, 3.87]
Analysis 2.2
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

2.1 Clomiphene Citrate

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.43 [0.02, 11.18]

2.2 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.61 [0.44, 5.89]

2.3 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

1.88 [0.32, 11.00]

3 Pregnancy rate per couple (all cycles) Show forest plot

6

517

Odds Ratio (M‐H, Fixed, 95% CI)

1.69 [1.14, 2.53]
Analysis 2.3
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

3.1 Clomiphene Citrate

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.30 [0.03, 2.93]

3.2 Gonadotropins

4

319

Odds Ratio (M‐H, Fixed, 95% CI)

1.68 [1.03, 2.75]

3.3 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

2.62 [0.98, 6.98]

3.4 Clomiphene citrate OR Gonadotropins

1

90

Odds Ratio (M‐H, Fixed, 95% CI)

1.72 [0.50, 5.89]

4 Moderate or severe ovarian hyperstimulation syndrome rate per woman Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.4
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome rate per woman.

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome rate per woman.

4.1 Gonadotropins

1

108

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

2.75 [0.11, 69.83]

5 Miscarriage rate per couple Show forest plot

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.66 [0.56, 4.88]
Analysis 2.5
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 5 Miscarriage rate per couple.

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 5 Miscarriage rate per couple.

5.1 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.66 [0.56, 4.88]

6 Ectopic pregnancy rate per couple Show forest plot

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

3.06 [0.12, 76.95]
Analysis 2.6
Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

6.1 Gonadotropins

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

3.06 [0.12, 76.95]
Open in table viewer
Comparison 3. IUI in natural cycle versus IUI in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

4

396

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.29, 0.82]
Analysis 3.1
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

1.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.27 [0.02, 3.41]

1.2 Gonadotropins

3

370

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.85]

2 Multiple pregnancy rate per couple Show forest plot

2

65

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.70]
Analysis 3.2
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

2.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Gonadotropins

1

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.70]

3 Pregnancy rate per couple (all cycles) Show forest plot

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.77]
Analysis 3.3
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

3.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.77]

4 Moderate or severe ovarian hyperstimulation syndrome per woman Show forest plot

3

185

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Analysis 3.4
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

4.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Gonadotropins

2

159

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Miscarriage rate per couple Show forest plot

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.19 [0.01, 5.20]
Analysis 3.5
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 5 Miscarriage rate per couple.

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 5 Miscarriage rate per couple.

5.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.19 [0.01, 5.20]

5.2 Gonadotropins

0

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Ectopic pregnancy rate per couple Show forest plot

2

250

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 3.02]
Analysis 3.6
Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

6.1 Gonadotropins

2

250

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 3.02]
Open in table viewer
Comparison 4. IUI in stimulated cycle versus TI or expectant management in natural cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

0.82 [0.45, 1.49]
Analysis 4.1
Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

2 Multiple pregnancy rate per couple Show forest plot

2

304

Odds Ratio (M‐H, Fixed, 95% CI)

2.0 [0.18, 22.34]
Analysis 4.2
Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

2.1 Clomiphene Citrate

1

51

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Clomiphene Citrate or Gonadotropins

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

2.0 [0.18, 22.34]

3 Pregnancy rate per couple (all cycles) Show forest plot

2

304

Odds Ratio (M‐H, Fixed, 95% CI)

1.00 [0.59, 1.67]
Analysis 4.3
Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

3.1 Clomiphene Citrate

1

51

Odds Ratio (M‐H, Fixed, 95% CI)

3.2 [0.82, 12.50]

3.2 Clomiphene Citrate or Gonadotropins

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

0.80 [0.45, 1.42]

4 Moderate or severe ovarian hyperstimulation syndrome per woman Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 4.4
Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

4.1 Clomiphene Citrate

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Clomiphene Citrate or Gonadotropins

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Miscarriage rate per couple Show forest plot

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

2.28 [0.84, 6.20]
Analysis 4.5
Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 5 Miscarriage rate per couple.

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 5 Miscarriage rate per couple.

Open in table viewer
Comparison 5. IUI in natural cycle versus TI or expectant management in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.95 [1.10, 3.44]
Analysis 5.1
Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

2 Multiple pregnancy rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.07, 16.90]
Analysis 5.2
Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

3 Pregnancy rate per couple (all cycles) Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.77 [1.01, 3.08]
Analysis 5.3
Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

4 Miscarriage rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.32, 2.58]
Analysis 5.4
Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 4 Miscarriage rate per couple.

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 4 Miscarriage rate per couple.

5 Ectopic pregnancy rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Random, 95% CI)

5.30 [0.25, 111.26]
Analysis 5.5
Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 5 Ectopic pregnancy rate per couple.

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 5 Ectopic pregnancy rate per couple.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figures and Tables -
Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figures and Tables -
Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Study flow diagram.
Figures and Tables -
Figure 3

Study flow diagram.

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Funnel plot of comparison: 2 IUI versus TI both in stimulated cycle, outcome: 2.3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Figure 4

Funnel plot of comparison: 2 IUI versus TI both in stimulated cycle, outcome: 2.3 Pregnancy rate per couple (all cycles).

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Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 1 Live birth rate per couple (all cycles).
Figures and Tables -
Analysis 1.1

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

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Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 2 Multiple pregnancy rate per couple.
Figures and Tables -
Analysis 1.2

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

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Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Analysis 1.3

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

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Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 4 Miscarriage rate per couple.
Figures and Tables -
Analysis 1.4

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 4 Miscarriage rate per couple.

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Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 5 Ectopic pregnancy rate per couple.
Figures and Tables -
Analysis 1.5

Comparison 1 IUI versus TI or expectant management both in natural cycle, Outcome 5 Ectopic pregnancy rate per couple.

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).
Figures and Tables -
Analysis 2.1

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.
Figures and Tables -
Analysis 2.2

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Analysis 2.3

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome rate per woman.
Figures and Tables -
Analysis 2.4

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome rate per woman.

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 5 Miscarriage rate per couple.
Figures and Tables -
Analysis 2.5

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 5 Miscarriage rate per couple.

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Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.
Figures and Tables -
Analysis 2.6

Comparison 2 IUI versus TI or expectant management both in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).
Figures and Tables -
Analysis 3.1

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.
Figures and Tables -
Analysis 3.2

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Analysis 3.3

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.
Figures and Tables -
Analysis 3.4

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 5 Miscarriage rate per couple.
Figures and Tables -
Analysis 3.5

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 5 Miscarriage rate per couple.

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Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.
Figures and Tables -
Analysis 3.6

Comparison 3 IUI in natural cycle versus IUI in stimulated cycle, Outcome 6 Ectopic pregnancy rate per couple.

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Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 1 Live birth rate per couple (all cycles).
Figures and Tables -
Analysis 4.1

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 1 Live birth rate per couple (all cycles).

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Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 2 Multiple pregnancy rate per couple.
Figures and Tables -
Analysis 4.2

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 2 Multiple pregnancy rate per couple.

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Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Analysis 4.3

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 3 Pregnancy rate per couple (all cycles).

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Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.
Figures and Tables -
Analysis 4.4

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 4 Moderate or severe ovarian hyperstimulation syndrome per woman.

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Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 5 Miscarriage rate per couple.
Figures and Tables -
Analysis 4.5

Comparison 4 IUI in stimulated cycle versus TI or expectant management in natural cycle, Outcome 5 Miscarriage rate per couple.

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Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).
Figures and Tables -
Analysis 5.1

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 1 Live birth rate per couple (all cycles).

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Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.
Figures and Tables -
Analysis 5.2

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 2 Multiple pregnancy rate per couple.

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Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).
Figures and Tables -
Analysis 5.3

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 3 Pregnancy rate per couple (all cycles).

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Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 4 Miscarriage rate per couple.
Figures and Tables -
Analysis 5.4

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 4 Miscarriage rate per couple.

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Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 5 Ectopic pregnancy rate per couple.
Figures and Tables -
Analysis 5.5

Comparison 5 IUI in natural cycle versus TI or expectant management in stimulated cycle, Outcome 5 Ectopic pregnancy rate per couple.

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Summary of findings for the main comparison. IUI compared to TI or expectant management both in natural cycle for unexplained subfertility

IUI compared to TI or expectant management both in natural cycle for unexplained subfertility

Patient or population: people with unexplained subfertility
Settings:
Intervention: IUI
Comparison: TI or expectant management both in natural cycle

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

TI or expectant management both in natural cycle

IUI

Live birth rate per couple (all cycles)

156 per 1000

228 per 1000
(145 to 339)

OR 1.60
(0.92 to 2.78)

334
(1 study)

⊕⊕⊕⊝
moderate1,2

Multiple pregnancy rate per couple

12 per 1000

6 per 1000
(0 to 63)

OR 0.50
(0.04 to 5.53)

334
(1 study)

⊕⊕⊕⊝
moderate1,2

Pregnancy rate per couple (all cycles)

162 per 1000

228 per 1000
(145 to 338)

OR 1.53
(0.88 to 2.64)

334
(1 study)

⊕⊕⊕⊝
moderate1,2

Ovarian Hyperstimulation Syndrome rate per woman ‐ not reported

Not estimable

‐

Miscarriage rate per couple

54 per 1000

42 per 1000
(16 to 107)

OR 0.77
(0.28 to 2.11)

334
(1 study)

⊕⊕⊕⊝
moderate1,2

Ectopic pregnancy rate per couple

Not estimable

OR 5.06
(0.24 to 106.2)

334
(1 study)

⊕⊕⊕⊝
moderate1,2

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Small sample size
2 Effect estimate with wide confidence interval

Figures and Tables -
Summary of findings for the main comparison. IUI compared to TI or expectant management both in natural cycle for unexplained subfertility
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Summary of findings 2. IUI compared to TI or expectant management both in stimulated cycle for unexplained subfertility

IUI compared to TI or expectant management both in stimulated cycle for unexplained subfertility

Patient or population: people with unexplained subfertility
Settings:
Intervention: IUI
Comparison: TI both in stimulated cycle

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

TI both in stimulated cycle

IUI

Live birth rate per couple (all cycles)

255 per 1000

352 per 1000
(231 to 496)

OR 1.59
(0.88 to 2.88)

208
(2 studies)

⊕⊕⊕⊝
moderate1,2

Multiple pregnancy rate per couple

43 per 1000

62 per 1000
(24 to 148)

OR 1.46
(0.55 to 3.87)

316
(4 studies)

⊕⊕⊝⊝
low2,3

Pregnancy rate per couple (all cycles)

234 per 1000

339 per 1000
(257 to 433)

OR 1.69
(1.14 to 2.53)

517
(7 studies)

⊕⊕⊝⊝
low1,2,3

Ovarian Hyperstimulation Syndrome rate per woman

not estimable

OR 2.75
(0.11 to 69.83)

68
(1 study)

⊕⊕⊝⊝
low2,3,4

Miscarriage rate per couple

57 per 1000

91 per 1000
(33 to 228)

OR 1.66
(0.56 to 4.88)

208
(2 studies)

⊕⊕⊕⊝
moderate1,2

Ectopic pregnancy rate per couple

not estimable

OR 3.06
(0.12 to 76.95)

100
(1 study)

⊕⊕⊕⊝
moderate1,2

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Small sample size
2 Effect estimate with wide confidence interval
3 Most domains of risk of bias were assessed as either 'unclear' or 'high risk'
4 Only one event in one study was reported

Figures and Tables -
Summary of findings 2. IUI compared to TI or expectant management both in stimulated cycle for unexplained subfertility
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Summary of findings 3. IUI in natural cycle compared to IUI in stimulated cycle for unexplained subfertility

IUI in natural cycle compared to IUI in stimulated cycle for unexplained subfertility

Patient or population: people with unexplained subfertility
Settings:
Intervention: IUI in natural cycle
Comparison: IUI in stimulated cycle

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

IUI in stimulated cycle

IUI in natural cycle

Live birth rate per couple (all cycles)

248 per 1000

137 per 1000
(87 to 213)

OR 0.48
(0.29 to 0.82)

396
(4 studies)

⊕⊕⊕⊝
moderate1,2

Multiple pregnancy rate per couple

33 per 1000

11 per 1000
(0 to 229)

OR 0.33
(0.01 to 8.7)

65
(2 studies)

⊕⊕⊝⊝
low1,2

Pregnancy rate per couple (all cycles)

300 per 1000

64 per 1000
(4 to 431)

OR 0.16
(0.01 to 1.77)

26
(1 study)

⊕⊕⊕⊝
moderate1,2

Ovarian Hyperstimulation Syndrome rate per woman5 ‐ not measured

Not estimable3

‐

Miscarriage rate per couple

100 per 1000

21 per 1000
(1 to 366)

OR 0.19
(0.01 to 5.2)

26
(1 study)

⊕⊕⊝⊝
low1,2

Ectopic pregnancy rate per couple

23 per 1000

4 per 1000
(0 to 66)

OR 0.15
(0.01 to 3.02)

250
(2 studies)

⊕⊕⊕⊝
moderate1,2

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Small sample size
2 Effect estimate with wide confidence interval
3 No usable data were reported

Figures and Tables -
Summary of findings 3. IUI in natural cycle compared to IUI in stimulated cycle for unexplained subfertility
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Summary of findings 4. IUI in stimulated cycle compared to TI or expectant management in natural cycle for unexplained subfertility

IUI in stimulated cycle compared to TI or expectant management in natural cycle for unexplained subfertility

Patient or population: people with unexplained subfertility
Settings:
Intervention: IUI in stimulated cycle
Comparison: TI or expectant management in natural cycle

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

TI or expectant management in natural cycle

IUI in stimulated cycle

Live birth rate per couple (all cycles)

238 per 1000

204 per 1000
(123 to 318)

OR 0.82
(0.45 to 1.49)

253
(1 study)

⊕⊕⊕⊝
moderate1,2

Multiple pregnancy rate per couple

6 per 1000

13 per 1000
(1 to 128)

OR 2.00
(0.18 to 22.34)

304
(2 studies)

⊕⊕⊕⊝
moderate1,2

Pregnancy rate per couple (all cycles)

247 per 1000

247 per 1000
(162 to 354)

OR 1.00
(0.59 to 1.67)

304
(2 studies)

⊕⊕⊕⊝
moderate1,2

Ovarian Hyperstimulation rate per woman ‐ not measured

Not estimable

‐

Miscarriage rate per couple

48 per 1000

103 per 1000
(41 to 238)

OR 2.28
(0.84 to 6.2)

253
(1 study)

⊕⊕⊕⊝
moderate1,2

Ectopic pregnancy rate per couple ‐ not reported

See comment

See comment

Not estimable

‐

See comment

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Small sample size
2 Effect estimate with wide confidence interval

Figures and Tables -
Summary of findings 4. IUI in stimulated cycle compared to TI or expectant management in natural cycle for unexplained subfertility
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Summary of findings 5. IUI in natural cycle compared to TI or expectant management in stimulated cycle for unexplained subfertility

IUI in natural cycle compared to TI or expectant management in stimulated cycle for unexplained subfertility

Patient or population: people with unexplained subfertility
Settings:
Intervention: IUI in natural cycle
Comparison: TI in stimulated cycle

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

TI in stimulated cycle

IUI in natural cycle

Live birth rate per couple (all cycles)

131 per 1000

227 per 1000
(142 to 341)

OR 1.95
(1.1 to 3.44)

342
(1 study)

⊕⊕⊕⊝
moderate1

Multiple pregnancy rate per couple

6 per 1000

6 per 1000
(0 to 88)

OR 1.05
(0.07 to 16.9)

342
(1 study)

⊕⊕⊕⊝
moderate1,2

Pregnancy rate per couple (all cycles)

143 per 1000

228 per 1000
(144 to 339)

OR 1.77
(1.01 to 3.08)

342
(1 study)

⊕⊕⊕⊝
moderate1

Ovarian Hyperstimulation Syndrome rate per woman ‐ not reported

Not estimable

‐

Miscarriage rate per couple

46 per 1000

42 per 1000
(15 to 111)

OR 0.91
(0.32 to 2.58)

342
(1 study)

⊕⊕⊕⊝
moderate1,2

Ectopic pregnancy rate per couple

Not estimable

OR 5.30
(0.25 to 111.3)

342
(1 study)

⊕⊕⊕⊝
moderate1,2

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Small sample size
2 Effect estimate with wide confidence interval

Figures and Tables -
Summary of findings 5. IUI in natural cycle compared to TI or expectant management in stimulated cycle for unexplained subfertility
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Comparison 1. IUI versus TI or expectant management both in natural cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [0.92, 2.78]

2 Multiple pregnancy rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.04, 5.53]

3 Pregnancy rate per couple (all cycles) Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

1.53 [0.88, 2.64]

4 Miscarriage rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

0.77 [0.28, 2.11]

5 Ectopic pregnancy rate per couple Show forest plot

1

334

Odds Ratio (M‐H, Fixed, 95% CI)

5.06 [0.24, 106.21]
Figures and Tables -
Comparison 1. IUI versus TI or expectant management both in natural cycle
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Comparison 2. IUI versus TI or expectant management both in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.59 [0.88, 2.88]

1.1 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.59 [0.88, 2.88]

2 Multiple pregnancy rate per couple Show forest plot

4

316

Odds Ratio (M‐H, Fixed, 95% CI)

1.46 [0.55, 3.87]

2.1 Clomiphene Citrate

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.43 [0.02, 11.18]

2.2 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.61 [0.44, 5.89]

2.3 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

1.88 [0.32, 11.00]

3 Pregnancy rate per couple (all cycles) Show forest plot

6

517

Odds Ratio (M‐H, Fixed, 95% CI)

1.69 [1.14, 2.53]

3.1 Clomiphene Citrate

1

40

Odds Ratio (M‐H, Fixed, 95% CI)

0.30 [0.03, 2.93]

3.2 Gonadotropins

4

319

Odds Ratio (M‐H, Fixed, 95% CI)

1.68 [1.03, 2.75]

3.3 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

2.62 [0.98, 6.98]

3.4 Clomiphene citrate OR Gonadotropins

1

90

Odds Ratio (M‐H, Fixed, 95% CI)

1.72 [0.50, 5.89]

4 Moderate or severe ovarian hyperstimulation syndrome rate per woman Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Gonadotropins

1

108

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Clomiphene Citrate and Gonadotropins

1

68

Odds Ratio (M‐H, Fixed, 95% CI)

2.75 [0.11, 69.83]

5 Miscarriage rate per couple Show forest plot

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.66 [0.56, 4.88]

5.1 Gonadotropins

2

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.66 [0.56, 4.88]

6 Ectopic pregnancy rate per couple Show forest plot

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

3.06 [0.12, 76.95]

6.1 Gonadotropins

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

3.06 [0.12, 76.95]
Figures and Tables -
Comparison 2. IUI versus TI or expectant management both in stimulated cycle
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Comparison 3. IUI in natural cycle versus IUI in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

4

396

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.29, 0.82]

1.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.27 [0.02, 3.41]

1.2 Gonadotropins

3

370

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.85]

2 Multiple pregnancy rate per couple Show forest plot

2

65

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.70]

2.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Gonadotropins

1

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.70]

3 Pregnancy rate per couple (all cycles) Show forest plot

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.77]

3.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.77]

4 Moderate or severe ovarian hyperstimulation syndrome per woman Show forest plot

3

185

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Gonadotropins

2

159

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Miscarriage rate per couple Show forest plot

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.19 [0.01, 5.20]

5.1 Clomiphene Citrate

1

26

Odds Ratio (M‐H, Fixed, 95% CI)

0.19 [0.01, 5.20]

5.2 Gonadotropins

0

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Ectopic pregnancy rate per couple Show forest plot

2

250

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 3.02]

6.1 Gonadotropins

2

250

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 3.02]
Figures and Tables -
Comparison 3. IUI in natural cycle versus IUI in stimulated cycle
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Comparison 4. IUI in stimulated cycle versus TI or expectant management in natural cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

0.82 [0.45, 1.49]

2 Multiple pregnancy rate per couple Show forest plot

2

304

Odds Ratio (M‐H, Fixed, 95% CI)

2.0 [0.18, 22.34]

2.1 Clomiphene Citrate

1

51

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Clomiphene Citrate or Gonadotropins

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

2.0 [0.18, 22.34]

3 Pregnancy rate per couple (all cycles) Show forest plot

2

304

Odds Ratio (M‐H, Fixed, 95% CI)

1.00 [0.59, 1.67]

3.1 Clomiphene Citrate

1

51

Odds Ratio (M‐H, Fixed, 95% CI)

3.2 [0.82, 12.50]

3.2 Clomiphene Citrate or Gonadotropins

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

0.80 [0.45, 1.42]

4 Moderate or severe ovarian hyperstimulation syndrome per woman Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 Clomiphene Citrate

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Clomiphene Citrate or Gonadotropins

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Miscarriage rate per couple Show forest plot

1

253

Odds Ratio (M‐H, Fixed, 95% CI)

2.28 [0.84, 6.20]
Figures and Tables -
Comparison 4. IUI in stimulated cycle versus TI or expectant management in natural cycle
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Comparison 5. IUI in natural cycle versus TI or expectant management in stimulated cycle

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate per couple (all cycles) Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.95 [1.10, 3.44]

2 Multiple pregnancy rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.07, 16.90]

3 Pregnancy rate per couple (all cycles) Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

1.77 [1.01, 3.08]

4 Miscarriage rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.32, 2.58]

5 Ectopic pregnancy rate per couple Show forest plot

1

342

Odds Ratio (M‐H, Random, 95% CI)

5.30 [0.25, 111.26]
Figures and Tables -
Comparison 5. IUI in natural cycle versus TI or expectant management in stimulated cycle
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