Unexplained infertility: An update and review of practice

Reproductive BioMedicine Online

Volumn 24, Issue 6, 2012, Pages 591-602

  Ray, Arpita ^a   Shah, Amit ^a   Gudi, Anil ^a   Homburg, Roy ^a  

^a HOMERTON UNIVERSITY HOSPITAL   (United Kingdom)

Author keywords

definitions; management options; prevalence; reasons; unexplained infertility

Indexed keywords

ANASTROZOLE; CHORIONIC GONADOTROPIN; CLOMIFENE CITRATE; LETROZOLE; PLACEBO;

AGE; ALGORITHM; CLINICAL PRACTICE; CLINICAL PROTOCOL; COCHRANE LIBRARY; COMPARATIVE EFFECTIVENESS; DISEASE DURATION; DRUG EFFICACY; EMBASE; FALLOPIAN TUBE SPERM PERFUSION; FERTILIZATION IN VITRO; GAMETE INTRAFALLOPIAN TRANSFER; HUMAN; INFERTILITY; INFERTILITY THERAPY; INTRAUTERINE INSEMINATION; MEDLINE; OVULATION INDUCTION; PREGNANCY RATE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TUBAL FLUSHING; UNEXPLAINED INFERTILITY;

FEMALE; FERTILIZATION IN VITRO; GAMETE INTRAFALLOPIAN TRANSFER; HUMANS; INFERTILITY; INSEMINATION, ARTIFICIAL; MALE; OVULATION INDUCTION; PREVALENCE; TERMINOLOGY AS TOPIC;

EID: 84861825692     PISSN: 14726483     EISSN: 14726491     Source Type: Journal    
DOI: 10.1016/j.rbmo.2012.02.021     Document Type: Review

References (91)

1. S. Agarwal, and S. Mittal A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene Indian J. Med. Res. 120 6 2004 519 522
2. A. Agic, H. Xu, D. Finas, C. Banz, K. Diedrich, and D. Hornung Is endometriosis associated with systemic subclinical inflammation? Gynecol. Obstet. Invest. 62 3 2006 139 147
3. H. Al-Fozan, M. Al-Khadouri, S.L. Tan, and T. Tulandi A randomized trial of letrozole versus clomiphene citrate in women undergoing super ovulation Fertil. Steril. 82 2004 1561 1563
4. L. Arcaini, S. Bianchi, A. Baglioni, M. Marchini, L. Tozzi, and L. Fedele Superovulation and intrauterine insemination vs. super ovulation alone in the treatment of unexplained infertility. A randomized study J. Reprod. Med. 416 1996 14 18
5. A. Arici, W. Byrd, K. Bradshaw, W.H. Kutteh, P. Marshburn, and B.R. Carr Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles Fertil. Steril. 61 2 1994 314 318
6. American Fertility Society Investigation of the Infertile Couple 1992 American Society for Reproductive Medicine Birmingham
7. ASRM Effectiveness and treatment of unexplained infertility the practice committee of the American Society for Reproductive Medicine Fertil. Steril. 86 2006
8. N. Athaullah, M. Proctor, and N. Johnson Oral versus injectable ovulation induction agents for unexplained sub fertility Cochrane Database Syst. Rev. 2002 Art. No. CD0 03052
9. N. Athaullah, M. Proctor, and N. Johnson Oral versus injectable ovulation induction agents for unexplained sub fertility Cochrane Database Syst. Rev. 2009 Art. No. CD003052
10. T. Bagist, B. Hayidaardedeoglu, E.B. Kilicdag, T. Cok, E. Simsek, and A.H. Parlakgumus Single versus double IUI multifollicular ovarian stimulation, a randomized trial Hum. Reprod. 25 7 2010 1684 1690
11. V.L. Baker, and G.D. Adamson Threshold intrauterine perfusion pressures for intra-peritoneal spill during hydrotubation and correlation with tubal adhesive disease Fertil. Steril. 64 1995 1066 1069
12. J. Balasch, J.L. Ballesca, C. Pimentel, M. Creus, F. Fabregues, and J.A. Vanrell Late low dose pure FSH for ovarian stimulation in intra-uterine insemination cycles Hum. Reprod. 10 1994 1863 1866
13. G. Barroso, G. Menocal, H. Felix, J.C. Rojas-Ruiz, M. Arslan, and S. Oehniger Comparisons of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyper stimulation: a prospective, randomized, blinded clinical trial Fertil. Steril. 86 2006 1428 1431
14. G.S. Berger Intratubal insemination Fertil. Steril. 48 1987 328 330
15. S. Bhattacharya, K. Harrild, J. Mollison, S. Woodworth, C. Tay, A. Harrold, D. McQueen, H. Lyall, L. Johnston, J. Burrage, S. Grossett, H. Walton, J. Lynch, A. Johnstone, S. Kini, A. Raja, and A. Templeton Clomiphene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial Br. Med. J. 337 2008 a716
16. C.P. Biacchiardi, A. Revelli, G. Gennarelli, S. Rustichelli, F. Moffa, and M. Massobrio Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized prospective crossover trial Fertil. Steril. 81 2004 448 451
17. R.F. Casper, and M.F. Mitwally Review; aromatase inhibitors for ovulation induction J. Clin. Endocrinol. Metab. 91 2006 760 771
18. C.C. Chung, R. Fleming, M.E. Jamieson, R.W.S. Yates, and J.R.T. Coutts Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility Hum. Reprod. 10 1995 3139 3141
19. J.A. Collins, and P.G. Crosignani Unexplained infertility: a review of diagnosis, prognosis, treatment efficacy and management Int. J. Obstet. Gynaecol. 39 4 1992 267 275
20. J.A. Collins, and T.C. Rowe Age of female partner is a prognostic factor in prolonged unexplained infertility: a multicentre study Fertil. Steril. 52 1989 15
21. J.A. Collins, E.A. Burrows, and A.R. Wilan The prognosis for live birth among untreated infertile couples Fertil. Steril. 64 1995 22 28
22. P.G. Crosignani, D.E. Walters, and A. Soliani The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report (Centre 19: Martinez, Amsterdam) Hum. Reprod. 6 1991 953 958
23. J.L. Deaton, M. Gibson, K.M. Blackmer, S.T. Nakajima, G.J. Badger, and J.R. Brumsted A randomized controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis Fertil. Steril. 54 1990 1083 1088
24. R. Echochard, C. Mathieu, D. Royere, G. Blache, M. Rabilloud, and J. Cyzba A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination Fertil. Steril. 73 2000 90 93
25. G.A. Edelstam, E. Andersson, A. Radestad, F. Flam, and C. Gottlieb The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis Hum. Reprod. 13 1998 1353 1356
26. G. Edelstam, A. Sjosten, K. Bjuresten, I. EK, K. Wanggren, and J. Spira A new rapid and effective method for treatment of unexplained infertility Hum. Reprod. 23 2008 852 856
27. J.M. Eimers, E.R. Te Velde, R. Gerritse, E.T. Vogelzang, C.W. Looman, and J.D. Habbema The prediction of the chance to conceive in subfertile couples Fertil. Steril. 61 1994 44 52
28. ESHRE Campus Course Report Prevention of twin pregnancies after IVF/ICSI by single embryo transfer Hum. Reprod. 16 2001 790 800
29. ESHRE, Task Force on Ethics and Law Ethical issues related to multiple pregnancies in medically assisted procreation Hum. Reprod. 18 2003 1976 1979
30. J.L.H. Evers Female sub fertility Lancet 360 2002 151 159
31. J.L. Evers, H.W. de Haas, J.A. Land, J.C. Dumoulin, and G.A. Dunselman Treatment-independent pregnancy rates in patients with severe reproductive disorders Hum. Reprod. 13 1998 1206 1209
32. H.M. Fatemi, E. Kolibianakis, H. Tournaye, M. Camus, A.C. Van Steirteghem, and P. Deveroey Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study Reprod. Biomed. Online 7 2003 543 546
33. P. Fisch, R.F. Casper, S.E. Brown, W. Wrixon, J.A. Collins, R.L. Reid, and C. Simpson Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin Fertil. Steril. 51 1989 828 833
34. S. Fujii, Y. Fukushi, A. Kagiya, S. Sato, and Y. Saito The effects of clomiphene citrate on normally ovulatory women Fertil. Steril. 68 1997 997 999
35. C.M.A. Glazener, N.J. Kelly, M.J.A. Weir, J.S.E. David, J.S. Cornes, and M.G.R. Hull The diagnosis of male infertility-prospective time-specific study of conception rates related to seminal analysis and post-coital sperm-mucus penetration and survival in otherwise unexplained infertility Hum. Reprod. 2 1987 665 671
36. C.M. Glazener, C. Coulson, P.A. Lambert, E.M. Watt, R.A. Hinton, N.G. Kelly, and M.G. Hull Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates Gynaecol. Endocrinol. 4 1990 75 83
37. N. Gleicher, and D. Barad Unexplained infertility: does it really exist? Hum. Reprod. 21 8 2006 1951 1955
38. N. Gleicher, B. Vanderlaan, D. Pratt, and V. Karande Background pregnancy rates in infertile population Hum. Reprod. 11 1996 1011 1012
39. C. Gnoth, P. Frank-Herrmann, G. Freundl, D. Godehardt, and E. Godehardt Time to pregnancy: results of the German prospective study and impact on the management of infertility Hum. Reprod. 18 2003 1959 1966
40. A.J. Goverde, J. McDonnell, J.P. Vermeiden, R. Schats, F.F. Rutten, and J. Schoemaker Intrauterine insemination or in-vitro fertilisation in idiopathic sub fertility and male sub fertility: a randomised trial and cost-effectiveness analysis Lancet 355 2000 13 18
41. D. Guzick, S. Carson, C. Coutifaris, J. Overstreet, and P. Factor Litvak Efficacy of superovulation and intrauterine insemination in the treatment of infertility New Engl. J. Med. 340 1999 177 183
42. D.S. Guzick, I. Grefenstette, K. Baffone, S.L. Berga, J.S. Krasnow, D.W. Stovall, and G.J. Naus Infertility evaluation in fertile women: a model for assessing the efficacy of infertility testing Hum. Reprod. 9 1994 2306 2310
43. D.S. Guzick, M.W. Sullivan, G.D. Adamson, M.I. Cedars, R.J. Falk, and E.P. Peterson Efficacy of treatment for unexplained infertility Fertil. Steril. 70 1998 207 213
44. R.F. Harrison, and R.R. O'Moore The use of clomiphene citrate with and without human chorionic gonadotropin Irish Med. J. 76 1983 273 274
45. HFEA, 2006-2007. Fertility problems and treatment - facts and figures, 212.49.193.187/cps/rde/xbcr/SID-3F57D79B-/hfea/facts-and-figures.pdf. HFEA Guide to Infertility 2006-2007.
46. P.M. Horvath, M. Bohrer, R.M. Shelden, and E. Kennmann The relationship of sperm parameters to cycle fecundity in super ovulated women undergoing intra uterine insemination Fertil. Steril. 52 1989 288 294
47. E.G. Hughes, M.L. Beecroft, V. Wilkie, L. Burville, P. Claman, I. Tummon, E. Greenblatt, M. Fluker, and K. Thorpe A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency Hum. Reprod. 19 2004 105 109
48. Hughes, E., Brown, J., Collins, J.J., Vanderkerchove, P., 2010. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst. Rev. Art. No.: CD000057. doi:10.1002/14651858.CD000057.
49. M.G. Hull, C.M. Glazener, N.J. Kelly, D.I. Conway, P.A. Foster, P.A. Hinton, C. Coulson, P.A. Lambert, E.A. Watt, and K.M. Desai Population study of causes, treatment, and outcome of infertility Br. Med. J. (Clin. Res. Ed.) 291 1693 1985 6510
50. P. Janko, P. Hruzik, J. Pruzinec, H. Saliba, and J. Zidzik Induction of ovulation with or without intrauterine insemination in cases of unexplained sterility Fertil. Steril. 70 1998 S442
51. R.B.S. Jansen, and J.C. Anderson Catheterisation of the fallopian tubes from the vagina Lancet 2 1987 309 310
52. Johnson, N., Vandekerckhve, P., Watson, A., Lilford, R., Harada, T., Hughes, E., 2005. Tubal flushing for sub fertility. Cochrane Database Syst. Rev. 18. CD003718.
53. J. Kahn, A. Sun de, A. Koskemies, V. Von during, T. Sordal, F. Christensen, and K. Molne Fallopian tube sperm perfusion (FSP) versus intra -uterine insemination (IUI) in the treatment of unexplained infertility: a prospective randomized study Hum. Reprod. 8 1993 890 894
54. P.O. Karlström, T. Bergh, and O. Lundkvist A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotrophin or clomiphene citrate Fertil. Steril. 59 1993 554 559
55. E.A. Lenton, G.A. Weston, and I.D. Cooke Long term follow up of apparently normal couple with a complaint of infertility Fertil. Steril. 28 1977 913 919
56. G. Melis, A. Paoletti, F. Strigini, F. Fabris, D. Canale, and P. Fiorette Pharmacologic Induction of multiple follicular development improves the success rate of artificial insemination with husband's semen in couples with male-related or unexplained infertility Fertil. Steril. 47 1987 441 445
57. G.B. Melis, A.M. Paoletti, S. Ajossa, S. Guerriero, G.F. Depau, and V. Mais Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse Fertil. Steril. 64 1995 1088 1093 Available from: (Multiple Birth Minimisation Strategy)
58. A.P. Murdoch, M. Harris, M. Mahroo, M. Williams, and W. Dunlop Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility Br. J. Obstet. Gynaecol. 98 1991 1107 1111
59. National Institute of Clinical Excellence, 2004. Clinical Guideline 11 Fertility: assessment and treatment for people with fertility problems.
60. D. Nugent, A.J. Watson, S.R. Killick, A.H. Balen, and N.J. Rutherford A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility Fertil. Steril. 77 2002 173 175
61. M. Oak, E.N. Chantler, C.A. Vaughan Williams, and M. Elstein Sperm survival studies in peritoneal fluid from infertile women with endometriosis and unexplained infertility Clin. Reprod. Fertil. 3 1985 297 303
62. M.L. Oei, E.S. Surrey, B. McCaleb, and J.H. Kerin A prospective, randomized study of pregnancy rates after trans-uterotubal and intrauterine insemination Fertil. Steril. 58 1992 167 171
63. Pandian, Z., Bhattacharya, S., Vale, L., Templeton, A., 2005. In vitro fertilization for unexplained sub fertility. Cochrane Database Syst. Rev. Art. No.: CD003357. doi:10.1002/14651858.CD003357.
64. E.G. Papanikolaou, P. Humaidan, N. Polyzos, S. Kalantaridou, S. Kol, C. Benadiva, H. Tournaye, and B. Tarfatzis New algorithm for OHSS prevention Reprod. Biol. Endocrinol. 3 9 2011 147
65. N. Pashayan, G. Lyratzopoulos, and R. Mathur Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility BMC Health Ser. Res. 6 2006 801 811
66. A. Pellicer, C. Albert, A. Mercader, F. Bonilla-Musoles, J. Remohi, and C. Simon The follicular and endocrine environment in women with endometriosis; local and systematic cytokine production Fertil. Steril. 70 1998 425 431
67. Z. Philips, M. Barraza -Llorens, and J. Mand Ponsett Evaluation of the relative cost-effectiveness of treatments for infertility in the UK Hum. Reprod. 15 2000 95 106
68. N.P. Polyzos, S. Tzioras, D. Mauri, M. Tsappi, I. Cortinovis, L. Tsali, and G. Casazza Treatment of unexplained infertility with aromatase inhibitors or Clomiphene Citrate A systematic review and meta -analysis Obstet. Gynecol. Surv. 63 2008 472 479
69. D.E. Pratt, E. Bieber, R. Barnes, G. Shangold, E. Vignovic, and J. Shreiber Transvaginal fallopian tube sperm perfusion by tactile sensation: a preliminary report Fertil. Steril. 58 1991 167 171
70. M. Raneiri, V.A. Beckett, S. Marchant, A. Kinis, and P. Serhal Gamete intra fallopian transfer or in vitro fertilization after failed ovarian stimulation and intrauterine insemination in unexplained infertility Hum. Reprod. 10 1995 2023 2026
71. R.H. Reindollar, M.M. Regan, P.J. Neumann, P.J. Neumann, B.S. Levine, K.L. Thornton, M.M. Alper, and M.B. Goldman A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial Fertil. Steril. 94 2010 888 899
72. G. Ricci, G. Nucera, C. Pozzobon, R. Boscolo, E. Giolo, and S. Guaschino A simple method for fallopian tube sperm perfusion using a blocking device in the treatment of unexplained infertility Fertil. Steril. 76 2001 1242 1248
73. Royal College of Obstetricians and Gynaecologists Infertility Guideline Group, 1998. The Management of Infertility in Secondary Care. RCOG, London.
74. C.S. Sipe, W.A. Davis, M. Maifeld, and B.J. Van Voorhis A randomized trial comparing anastrozole and clomiphene citrate in an ovulation induction protocol using gonadotropins Fertil. Steril. 86 2006 1676 1681
75. S. Smith, S.M. Pfiefer, and J. Collins Diagnosis and management of female infertility JAMA 290 2003 17
76. H.K.A. Snick, T.S. Snick, J.L.H. Evers, and J.A. Collins The spontaneous pregnancy prognosis in untreated sub fertile couples: the Walcheren primary care study Hum. Reprod. 12 1997 1582 1588
77. S. Soliman, S. Daya, J. Collins, and J. Jarrell A randomised trial of in vitro fertilisation versus conventional treatment for infertility Fertil. Steril. 59 1993 1239 1244
78. P. Steures, J.W. Van der Steeg, P.G. Hompes, J.D. Habbema, M.J. Eijkemans, F.J. Broekmans, H.R. Verhoeve, P.M. Bossuyt, F. Vander Veen, and B.W. Mol Intrauterine insemination with controlled ovarian hypertimulation versus expectant management for couples with unexplained sub fertility and an intermediate prognosis; a randomised clinical trial Lancet 368 2006 216 221
79. J.A. Stewart Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained infertility Hum. Reprod. 18 2003 903 914
80. A.M. Stolwijk, G.A. Zielhuis, C.J. Hamilton, H. Straatman, J.M. Hollanders, H.J. Goverde, P.A. Van Dop, and A.L. Verbeek Prognostic models for the probability of achieving an on going pregnancy after in-vitro fertilization and the importance of testing their predictive value Hum. Reprod. 11 1996 2298 2303
81. A.M. Stolwijk, A.M. Wetzels, and D.D. Braat Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilisation and intra cytoplasmic sperm injection according to women's age, sub fertility diagnosis and primary or secondary sub fertility Hum. Reprod. 15 2000 203 209
82. T. Tanbo, P.O. Dale, and T. Abyholm Assisted fertilization in infertile women with patent fallopian tubes. A comparison of in-vitro fertilization, gamete intra-Fallopian transfer and tubal embryo stage transfer Hum. Reprod. 3 1990 266 270
83. A.A. Templeton, and G.C. Penny The incidence, characteristics, and prognosis of patients whose infertility is unexplained Fertil. Steril. 37 1982 175 182
84. A.A. Templeton, S. Bhattacharya, and M. Hamilton Management of Infertility for the MRCOG and Beyond 2000 RCOG Press London
85. The Practice Committee of the American Society for Reproductive Medicine Educational Bulletin Effectiveness and treatment for unexplained infertility Fertil. Steril. 86 2006 1111 1114
86. A. Tsafrir, A. Simon, E.J. Margalioth, and N. Laufer What should be the first-line treatment for unexplained infertility in women over 40 years of age-ovulation induction and IUI, or IVF? Reprod. Biomed. Online 19 2009 4334
87. Veltman-Verhulst, S.M., Cohlen, B.J., Hughes, E., Heineman, M.J., 2009. Intra-uterine insemination for unexplained infertility. Cochrane Database Syst. Rev., Art. No. CD001838.
88. A. Watson, P. Vandekerckhove, R. Lilford, A. Vail, I. Brosens, and E. Hughes A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result? Fertil. Steril. 61 1994 470 477
89. S. Wordsworth, J. Buchanan, J. Mollison, K. Harrild, L. Robertson, C. Tay, A. Harrold, D. McQueen, H. Lyall, L. Johnston, J. Burrage, S. Grossett, H. Walton, J. Lynch, A. Johnstone, S. Kini, A. Raja, A. Templeton, and S. Bhattacharya Clomiphene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective? Hum. Reprod. 26 2011 369 375
90. H.H. Wu, N.M. Wang, and M.L. Cheng A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility Gynaecol. Endocrinol. 23 2007 76 81
91. K. Zikopoulos, C.P. West, P.W. Thong, E.M. Kacser, J. Morrison, and F.C. Wu Homologous intra uterine insemination has no advantage over timed natural intercourse when used in combination with ovulation induction for the treatment of unexplained infertility Hum. Reprod. 8 1993 563 567