Skip to main content Accessibility help
×
Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-27T23:40:38.404Z Has data issue: false hasContentIssue false

Chapter 6 - Unexplained Infertility

Published online by Cambridge University Press:  25 February 2021

Siladitya Bhattacharya
Affiliation:
University of Aberdeen
Mark Hamilton
Affiliation:
University of Aberdeen
Get access

Summary

Unexplained infertility refers to the inability to conceive within 12 months of unprotected intercourse, not attributable to any known causes of infertility such as ovulatory dysfunction, reduced sperm quality, tubal pathology or other causes. Treatment for unexplained infertility can be done predominantly through intrauterine insemination with or without hyperstimulation or in vitro fertilisation. Given that these treatments are utilised to improve likelihood of conception in relation to the couple’s chances of spontaneous pregnancy, rather than targeting any specific pathology, a comparison should be drawn between these treatments and their natural conception prognosis. Utilisation of prognostic models can allow differentiation between those likely to benefit from immediate treatment from such individuals who have reasonable natural conception prognosis and thereby can delay treatment for 6 months in hopes of spontaneous pregnancy. This comparison is valuable given the aforementioned treatments have implications for both the woman and her future child, and the cost of such procedures also compromises care accessibility.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

Thoma, ME, McLain, AC, Louis, JF, King, RB, Trumble, AC, Sundaram, R, et al. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99(5):1324e31.e1321.CrossRefGoogle Scholar
Te Velde, ER, Eijkemans, MJC, Habbema, JDF. Variation in couple fecundity and time to pregnancy, an essential concept in human reproduction. Lancet. 2000;355:1928e9.CrossRefGoogle ScholarPubMed
National Institute for Health and Care Excellence. Fertility: assessment and treatment for people with fertility problems. NICE Clinical Guideline; 2013. Available at: www.nice.org.uk/guidance/cg156/resources/%0Dupdated-niceguidelines-revise-treatment-recommendations-for-peoplewith-%0Dfertility-problemsGoogle Scholar
Brandes, M, Hamilton, CJCM, de Bruin, JP, Nelen, WLDM, Kremer, JAM. The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort. Hum Reprod. 2010;25(1):118e26.CrossRefGoogle Scholar
ESHRE. Guidelines for counseling infertility. 2001.Google Scholar
Hunault, CC, Habbema, JDF, Eijkemans, MJC, Collins, JA, Evers, JLH, te Velde, ER. Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couples, based on the synthesis of three previous models. Hum Reprod. 2004;19:2019e26.CrossRefGoogle ScholarPubMed
van der Steeg, JW, Steures, P, Eijkemans, MJC, Habbema, JDF, Hompes, PGA, Broekmans, FJ, et al. Pregnancy is predictable: a large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples. Hum Reprod. 2006;22:536e42.Google ScholarPubMed
Bostofte, E, Bagger, P, Michael, A, Stakemann, G. Fertility prognosis for infertile couples. Fertil Steril. 1993;59:102e7.CrossRefGoogle ScholarPubMed
Snick, HK, Snick, TS, Evers, JL, Collins, JA. The spontaneous pregnancy prognosis in untreated subfertile couples: the Walcheren primary care study. Hum Reprod. 1997;12:1582e8.CrossRefGoogle ScholarPubMed
Collins, JA, Burrows, EA, Wilan, AR. The prognosis for live birth among untreated infertile couples. Fertil Steril. 1995;64: 22e8.Google Scholar
Eimers, JM, te Velde, ER, Gerritse, R, Vogelzang, ET, Looman, CW, Habbema, JDF. The prediction of the chance to conceive in subfertile couples. Fertil Steril. 1994;61:44e52.CrossRefGoogle ScholarPubMed
Bahamondes, L, Alma, FA, Faundes, A, Vera, S. Score prognosis for the infertile couple based on historical factors and sperm analysis. Int J Gynaecol Obstet. 1994;46:311e5.CrossRefGoogle ScholarPubMed
Wichmann, L, Isola, J, Tuohimaa, P. Prognostic variables in predicting pregnancy: a prospective follow up study of 907 couples with an infertility problem. Hum Reprod. 1994;9:1102e8.CrossRefGoogle ScholarPubMed
Bloomington MN. Institute for clinical systems improvement (ICSI). Diagnosis and management of basic infertility; 2004. Available at: www.guideline.gov/Google Scholar
Stolwijk, AM, Zielhuis, GA, Hamilton, CJ, Straatman, H, Hollanders, JM, Goverde, HJ, et al. Prognostic models for the probability of achieving an ongoing pregnancy after in-vitro fertilization and the importance of testing their predictive value. Hum Reprod. 1996;11:2298e303.CrossRefGoogle ScholarPubMed
Wasson, JH, Sox, HC, Neff, RK, Goldman, L. Clinical prediction rules: applications and methodological standards. N Engl J Med. 1985;313:793e9.CrossRefGoogle ScholarPubMed
Bleeker, SE, Moll, HA, Steyerberg, EW, Donders, AR, Derksen-Lubsen, G, Grobbee, DE, et al. External validation is necessary in prediction research: a clinical example. J Clin Epidemiol. 2003;56:826e32.CrossRefGoogle ScholarPubMed
Bensdorp, AJ, van der Steeg, JW, Steures, P, Habbema, JDF, Hompes, PGA, Bossuyt, PMM, et al., CECERM Study Group. A revised prediction model for natural conception. Reprod Biomed Online. 2017;34(6):619e26.CrossRefGoogle ScholarPubMed
Veltman-Verhulst, SM, Hughes, E, Ayeleke, RO, Cohlen, BJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev. 2016;2:Cd001838.Google ScholarPubMed
Farquhar, CM, Liu, E, Armstrong, S, Arroll, N, Lensen, S, Brown, J. Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial. Lancet. 2018;391:441e50.CrossRefGoogle ScholarPubMed
van den Boogaard, NM, Bensdorp, AJ, Oude Rengerink, K, Barnhart, K, Bhattacharya, S, Custers, IM, et al. Prognostic profiles and the effectiveness of assisted conception: secondary analyses of individual patient data. Hum Reprod Update. 2014;20(1):141–51.CrossRefGoogle ScholarPubMed
Hughes, EG, Beecroft, ML, Wilkie, V, Burville, L, Claman, P, Tummon, I, et al. A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency. Hum Reprod. 2004;19:1105e9.Google ScholarPubMed
Pandian, Z, Gibreel, A, Bhattacharya, S. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2015: Cd003357.CrossRefGoogle Scholar
Gnoth, C, Godehardt, D, Godehardt, E, Frank-Herrmann, P, Freundl, G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod. 2003;18:1959e66.CrossRefGoogle ScholarPubMed
Weir, WC, Weir, DR. Therapeutic value of salpingograms in infertility. Fertil Steril. 1951;2(6):514–22.CrossRefGoogle ScholarPubMed
Johnson, NP, Farquhar, CM, Hadden, WE, Suckling, J, Yu, Y, Sadler, L. The FLUSH trial–flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomized trial. Hum Reprod. 2004;19(9):2043–51.Google Scholar
Nugent, D, Watson, AJ, Killick, SR, Balen, AH, Rutherford, AJ. A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility. Fertil Steril. 2002;77(1):173–5.CrossRefGoogle ScholarPubMed
Ogata, R, Nakamura, G, Uchiumi, Y, Yokoyamay, M, Watanabe, Y, Nozaki, M, et al. Therapeutic efficacy of hysterosalpingography (HSG) in infertility, a prospective, randomized, clinical study. Jpn J Fertil Steril. 1993; 38:9194.Google Scholar
Mohiyiddeen, L, Hardiman, A, Fitzgerald, C, Hughes, E, Mol, BWJ, Johnson, N, et al. Tubal flushing for subfertility. Cochrane Database Syst Rev. 2015(5):CD003718.Google Scholar
Dreyer, K, van Rijswijk, J, Mijatovic, V, Goddijn, M, Verhoeve, HR, van Rooij, IAJ, et al. Oil-based or water-based contrast for hysterosalpingography in infertile women. N Engl J Med. 2017;376(21):2043–52.Google Scholar
Ramlau-Hansen, CH, Thulstrup, AM, Nohr, EA, Bonde, JP, Sørensen, TI, Olsen, J. Subfecundity in overweight and obese couples. Hum Reprod. 2007;22:1634–7.CrossRefGoogle ScholarPubMed
van der Steeg, JW, Steures, P, Eijkemans, MJ, Habbema, JDF, Hompes, PGA, Burggraaff, JM, et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod. 2008;23:324–8.Google ScholarPubMed
Rich-Edwards, JW, Goldman, MB, Willett, WC, Hunter, DJ, Stampfer, MJ, Colditz, GA, et al. Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol. 1994;171:171–7.CrossRefGoogle ScholarPubMed
Legro, RS, Barnhart, HX, Schlaff, WD, Carr, BR, Diamond, MP, Carson, SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551–66.CrossRefGoogle ScholarPubMed
Rittenberg, V, Seshadri, S, Sunkara, SK, Sobaleva, S, Oteng-Ntim, E, El-Toukhy, T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011;23:421–39.CrossRefGoogle ScholarPubMed
Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril. 2015;104:1116–26.Google Scholar
National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. London: RCOG Press, 2004.Google Scholar
Mutsaerts, MAQ, van Oers, AM, Groen, H, Burggraaff, JM, Kuchenbecker, WKH, Perquin, DAM, et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med. 2016;374(20):1942–53.CrossRefGoogle ScholarPubMed
Kupka, MS, D’Hooghe, T, Ferraretti, AP, de Mouzon, J, Erb, K, Castilla, JA, et al. Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. Hum Reprod. 2016;31:dev319.Google ScholarPubMed
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;355:13e8.CrossRefGoogle ScholarPubMed
Custers, IM, K€onig, TE, Broekmans, FJ, Hompes, PGA, Kaaijk, E, Oosterhuis, J, et al. Couples with unexplained subfertility and unfavorable prognosis: a randomized pilot trial comparing the effectiveness of in vitro fertilization with elective single embryo transfer versus intrauterine insemination with controlled ovarian stimulation. Fertil Steril. 2011;96:1107e11011.e1.CrossRefGoogle ScholarPubMed
Gameiro, S, Boivin, J, Peronace, L, Verhaak, CM. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment. Hum Reprod Update. 2012;18:652e69.Google Scholar
van Rumste, MME, Custers, IM, van Wely, M, Koks, CA, van Weering, HGI, Beckers, NGM, et al. IVF with planned single embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis. Reprod Biomed Online. 2014;28:336e42.CrossRefGoogle ScholarPubMed
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;350:g7771.CrossRefGoogle ScholarPubMed
Tjon-Kon-Fat, RI, Bensdorp, AJ, Bossuyt, PM, Koks, C, Oosterhuis, GJ, Hoek, A, et al. Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation? Hum Reprod. 2015;30(10):2331e9.Google Scholar
Bahadur, G, Homburg, R, Muneer, A, Racich, P, Alangaden, T, Al-Habib, A, et al. First line fertility treatment strategies regarding IUI and IVF require clinical evidence. Hum Reprod. 2016;31:1141e6.CrossRefGoogle ScholarPubMed
Deaton, JL, Gibson, M, Blackmer, KM, Nakajima, ST, Badger, GJ, Brumsted, JR. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril. 1990;54:1083e8.CrossRefGoogle ScholarPubMed
Steures, P, van der Steeg, JW, Hompes, PG, Habbema, JD, Eijkemans, MJ, Broekmans, FJ, et al. Collaborative effort on the clinical evaluation in reproductive medicine. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Lancet. 2006;368:216e21.CrossRefGoogle Scholar
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;337:a716.CrossRefGoogle ScholarPubMed
Reindollar, RH, Regan, MM, Neumann, PJ, Levine, BS, Thornton, KL, Alper, MM, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94:888e99.CrossRefGoogle ScholarPubMed
Troude, P, Bailly, E, Guibert, J, Bouyer, J, de la Rochebrochard, E, DAIFI Group. Spontaneous pregnancies among couples previously treated by in vitro fertilization. Fertil Steril. 2012;98:63e8.CrossRefGoogle ScholarPubMed
van Dongen, AJ, Verhagen, TE, Dumoulin, JC, Land, JA, Evers, JL. Reasons for dropping out from a waiting list for in vitro fertilization. Fertil Steril. 2010;94:1713e6.CrossRefGoogle ScholarPubMed
Farquhar, CM, van den Boogaard, NM, Riddell, C, Macdonald, A, Chan, E, Mol, BW. Accessing fertility treatment in New Zealand: a comparison of the clinical priority access criteria with a prediction model for couples with unexplained subfertility. Hum Reprod. 2011;26:3037e44.Google Scholar
Eijkemans, MJ, Lintsen, AM, Hunault, CC, Bouwmans, CA, Hakkaart, L, Braat, DD, et al. Pregnancy chances on an IVF/ICSI waiting list: a national prospective cohort study. Hum Reprod. 2008 Jul;23(7):1627e32.CrossRefGoogle Scholar
Pandey, S, Shetty, A, Hamilton, M, Bhattacharya, S, Maheshwari, A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18:485e503.Google Scholar
Bergh, C. Single embryo transfer: a mini-review. Hum Reprod. 2005;2:323e7.Google Scholar
ESHRE. ART (assisted reproductive technology) fact sheet. Internet site ESHRE. Available at: www.eshre.eu/annual_meeting/page.aspx/1367Google Scholar
Jackson, RA, Gibson, KA, Wu, YW, Croughan, MS. Perinatal outcomes in singletons following in vitro fertilization: a metaanalysis. Obstet Gynecol. 2004;103:551e63.CrossRefGoogle ScholarPubMed
Helmerhorst, FM, Perquin, DAM, Donker, D, Keirse, MJNC. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004;328:261.CrossRefGoogle Scholar
Barnhart, KT. Assisted reproductive technologies and perinatal morbidity: interrogating the association. Fertil Steril. 2013; 99:299e302.Google Scholar
Maheshwari, A, Pandey, S, Shetty, A, Hamilton, M, Bhattacharya, S. Obstetric and Perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in-vitro fertilisation treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98:368e77.CrossRefGoogle ScholarPubMed
Rumbold, AR, Moore, VM, Whitrow, MJ, Oswald, TK, Moran, LJ, Fernandez, RC, et al. The impact of specific fertility treatments on cognitive development in childhood and adolescence: a systematic review. Hum Reprod. 2017;32:1489e507.CrossRefGoogle ScholarPubMed
Davies, MJ, Rumbold, AR, Marino, JL, Willson, K, Giles, LC, Whitrow, MJ, et al. Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study. BJOG. 2017;124:1537e44.CrossRefGoogle ScholarPubMed
Dar, S, Librach, CL, Gunby, J, Bissonnette, F, Cowan, L, IVF Directors Group of Canadian Fertility and Andrology Society. Increased risk of preterm birth in singleton pregnancies after blastocyst versus Day 3 embryo transfer: Canadian ART Register (CARTR) analysis. Hum Reprod. 2013;28:924e8.CrossRefGoogle ScholarPubMed
K€allen, B, Finnstr€om, O, Lindam, A, Nilsson, E, Nygren, K-G, Olausson, PO. Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril. 2010;94:1680e3.Google ScholarPubMed
Kansal Kalra, S, Ratcliffe, SJ, Barnhart, KT, Coutifaris, C. Extended embryo culture and an increased risk of preterm delivery. Obstet Gynecol. 2012;120:69e75.Google Scholar
Scherrer, U, Rimoldi, SF, Rexhaj, E, Stuber, T, Duplain, H, Garcin, S, et al. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation. 2012;125(15):1890e6.CrossRefGoogle ScholarPubMed
Hart, R, Norman, RJ. The longer-term health outcomes for children born as a result of IVF treatment: Part I-General health outcomes. Hum Reprod Update. 2013;19:232e43.Google ScholarPubMed

Further Reading

Bensdorp, AJ, van der Steeg, JW, Steures, P, Habbema, JDF, Hompes, PGA, Bossuyt, PMM, et al., CECERM Study Group. A revised prediction model for natural conception. Reprod Biomed Online. 2017 Jun;34(6):619e26.CrossRefGoogle ScholarPubMed
Farquhar, CM, Liu, E, Armstrong, S, Arroll, N, Lensen, S, Brown, J. Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial. Lancet. 2018;391:441e50.CrossRefGoogle ScholarPubMed
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;355:13e8.CrossRefGoogle ScholarPubMed
Hughes, EG, Beecroft, ML, Wilkie, V, Burville, L, Claman, P, Tummon, I, et al. A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency. Hum Reprod. 2004;19:1105e9.Google ScholarPubMed
Pandey, S, Shetty, A, Hamilton, M, Bhattacharya, S, Maheshwari, A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18:485e503.CrossRefGoogle ScholarPubMed
Reindollar, RH, Regan, MM, Neumann, PJ, Levine, BS, Thornton, KL, Alper, MM, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94: 888e99.CrossRefGoogle ScholarPubMed
van der Steeg, JW, Steures, P, Eijkemans, MJC, Habbema, JDF, Hompes, PGA, Broekmans, FJ, et al. Pregnancy is predictable: a large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples. Hum Reprod. 2006;22:536e42.Google ScholarPubMed
Veltman-Verhulst, SM, Hughes, E, Ayeleke, RO, Cohlen, BJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev. 2016;2:Cd001838.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×