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Special characteristics, reproductive, and clinical profile of women with unexplained infertility versus other causes of infertility: a comparative study

  • Assisted Reproduction Technologies
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Abstract

Purpose

To investigate whether women with unexplained infertility (UI) demonstrate different demographic and IVF characteristics compared to those with other causes of infertility.

Methods

Data on 245 couples that underwent a total of 413 IVF/ICSI cycles were analyzed (UI 114 cycles, 73 women; anovulation (PCO/PCOS) 83 cycles, 51 women; tubal factor 85 cycles, 47 women; male factor 131 cycles, 74 women). Features of UI were compared versus other infertility groups, after adjustment for multiple comparisons. Generalized least squares (GLS) and random-effects logistic regression analysis were also performed.

Results

Live birth rates, consisting of the primary outcome, were similar in all compared infertility groups. Compared to male infertility, UI was associated with woman’s older age at cycle, lower body mass index (BMI), and higher follicle-stimulating hormone (FSH). Compared to tubal infertility, UI was linked to lower endometrial thickness at oocyte retrieval and lower BMI; compared to anovulatory infertility related to PCO/PCOS, UI was linked to woman’s older age, more frequent smoking, and poorer ovarian reserve tests (FSH and antral follicle count). After adjustment for other types of infertility, woman’s age, age at menarche, and FSH levels, anovulatory infertility presented with higher odds of clinical pregnancy compared to UI (adjusted OR = 2.13, 95% C: 1.01–4.52).

Conclusions

Infertile women with UI undergoing assisted reproduction demonstrate different demographic and clinical characteristics compared to those of other causes of infertility, albeit live birth rates are similar.

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References

  1. Siristatidis C, Bhattacharya S. Unexplained infertility: does it really exist? Does it matter? Hum Reprod. 2007;22(8):2084–7. https://doi.org/10.1093/humrep/dem117.

    Article  PubMed  Google Scholar 

  2. Collins JA, Crosignani PG. Unexplained infertility: a review of diagnosis, prognosis, treatment efficacy and management. Int J Gynaecol Obstet. 1992;39(4):267–75. https://doi.org/10.1016/0020-7292(92)90257-j.

    Article  CAS  PubMed  Google Scholar 

  3. Somigliana E, Paffoni A, Busnelli A, Filippi F, Pagliardini L, Vigano P, et al. Age-related infertility and unexplained infertility: an intricate clinical dilemma. Hum Reprod. 2016;31(7):1390–6. https://doi.org/10.1093/humrep/dew066.

    Article  PubMed  Google Scholar 

  4. Zayed F, Abu-Heija A. The management of unexplained infertility. Obstet Gynecol Surv. 1999;54(2):121–30.

    Article  CAS  Google Scholar 

  5. Taylor PJ, Collins JA. Unexplained infertility. Oxford: Oxford University Press; 1992.

    Google Scholar 

  6. Buckett W, Sierra S. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. Reprod BioMed Online. 2019;39:633–40. https://doi.org/10.1016/j.rbmo.2019.05.023.

    Article  PubMed  Google Scholar 

  7. Gunn DD, Bates GW. Evidence-based approach to unexplained infertility: a systematic review. Fertil Steril. 2016;105(6):1566–74 e1. https://doi.org/10.1016/j.fertnstert.2016.02.001.

    Article  PubMed  Google Scholar 

  8. Nandi A, Gudi A, Shah A, Homburg R. An online survey of specialists’ opinion on first line management options for unexplained subfertility. Hum Fertil (Camb). 2015;18(1):48–53. https://doi.org/10.3109/14647273.2014.948081.

    Article  Google Scholar 

  9. Evers JL, de Haas HW, Land JA, Dumoulin JC, Dunselman GA. Treatment-independent pregnancy rate in patients with severe reproductive disorders. Hum Reprod. 1998;13(5):1206–9. https://doi.org/10.1093/humrep/13.5.1206.

    Article  CAS  PubMed  Google Scholar 

  10. Wang R, Danhof NA, Tjon-Kon-Fat RI, Eijkemans MJ, Bossuyt PM, Mochtar MH, et al. Interventions for unexplained infertility: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2019;9:CD012692. https://doi.org/10.1002/14651858.CD012692.pub2.

    Article  PubMed  Google Scholar 

  11. 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. https://doi.org/10.1093/humupd/dmt035.

    Article  PubMed  Google Scholar 

  12. Tjon-Kon-Fat RI, Tajik P, Zafarmand MH, Bensdorp AJ, Bossuyt PMM, Oosterhuis GJE, et al. IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers. Hum Reprod. 2017;32(5):1028–32. https://doi.org/10.1093/humrep/dex037.

    Article  CAS  PubMed  Google Scholar 

  13. Gleicher N, Barad D. Unexplained infertility: does it really exist? Hum Reprod. 2006;21(8):1951–5. https://doi.org/10.1093/humrep/del135.

    Article  CAS  PubMed  Google Scholar 

  14. Abrahami N, Izhaki I, Younis JS. Do young women with unexplained infertility show manifestations of decreased ovarian reserve? J Assist Reprod Genet. 2019;36(6):1143–52. https://doi.org/10.1007/s10815-019-01467-0.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Goverde AJ, McDonnell J, Schats R, Vermeiden JP, Homburg R, Lambalk CB. Ovarian response to standard gonadotrophin stimulation for IVF is decreased not only in older but also in younger women in couples with idiopathic and male subfertility. Hum Reprod. 2005;20(6):1573–7. https://doi.org/10.1093/humrep/deh827.

    Article  CAS  PubMed  Google Scholar 

  16. Altmae S, Martinez-Conejero JA, Salumets A, Simon C, Horcajadas JA, Stavreus-Evers A. Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility. Mol Hum Reprod. 2010;16(3):178–87. https://doi.org/10.1093/molehr/gap102.

    Article  CAS  PubMed  Google Scholar 

  17. Leach RE, Moghissi KS, Randolph JF, Reame NE, Blacker CM, Ginsburg KA, et al. Intensive hormone monitoring in women with unexplained infertility: evidence for subtle abnormalities suggestive of diminished ovarian reserve. Fertil Steril. 1997;68(3):413–20. https://doi.org/10.1016/s0015-0282(97)00222-7.

    Article  CAS  PubMed  Google Scholar 

  18. Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693–7. https://doi.org/10.1136/bmj.291.6510.1693.

    Article  CAS  Google Scholar 

  19. Vogiatzi P, Pouliakis A, Siristatidis C. An artificial neural network for the prediction of assisted reproduction outcome. J Assist Reprod Genet. 2019;36(7):1441–8. https://doi.org/10.1007/s10815-019-01498-7.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Siristatidis C, Askoxylaki M, Varounis C, Kassanos D, Chrelias C. E-selectin, resistin and reactive oxygen species levels in GnRH -agonist and -antagonist protocols in IVF/ICSI: a prospective cohort study. J Assist Reprod Genet. 2015;32(6):959–67. https://doi.org/10.1007/s10815-015-0489-z.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45. https://doi.org/10.1093/humupd/dmp048.

    Article  PubMed  Google Scholar 

  22. Siristatidis C, Dafopoulos K, Christoforidis N, Anifandis G, Pergialiotis V, Papantoniou N. Corifollitropin alfa compared with follitropin beta in GnRH-antagonist ovarian stimulation protocols in an unselected population undergoing IVF/ICSI. Gynecol Endocrinol. 2017;33(12):968–71. https://doi.org/10.1080/09513590.2017.1323203.

    Article  CAS  PubMed  Google Scholar 

  23. Murto T, Bjuresten K, Landgren BM, Stavreus-Evers A. Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility. Reprod Biol Endocrinol. 2013;11:61. https://doi.org/10.1186/1477-7827-11-61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kolstad HA, Bonde JP, Hjollund NH, Jensen TK, Henriksen TB, Ernst E, et al. Menstrual cycle pattern and fertility: a prospective follow-up study of pregnancy and early embryonal loss in 295 couples who were planning their first pregnancy. Fertil Steril. 1999;71(3):490–6. https://doi.org/10.1016/s0015-0282(98)00474-9.

    Article  CAS  PubMed  Google Scholar 

  25. Brodin T, Bergh T, Berglund L, Hadziosmanovic N, Holte J. Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization. Fertil Steril. 2008;90(5):1656–61. https://doi.org/10.1016/j.fertnstert.2007.09.036.

    Article  PubMed  Google Scholar 

  26. te Velde ER, Pearson PL. The variability of female reproductive ageing. Hum Reprod Update. 2002;8(2):141–54. https://doi.org/10.1093/humupd/8.2.141.

    Article  Google Scholar 

  27. Yücel B, Kelekci S, Demirel E. Decline in ovarian reserve may be an undiagnosed reason for unexplained infertility: a cohort study. Arch Med Sci. 2016;14(3):527–31. https://doi.org/10.5114/aoms.2016.58843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Simoni M, Nieschlag E, Gromoll J. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Hum Reprod Update. 2002;8(5):413–21. https://doi.org/10.1093/humupd/8.5.413.

    Article  CAS  PubMed  Google Scholar 

  29. Randolph JF, Ginsburg KA, Leach RE, Blacker CM, Moghissi KS, Diamond MP, et al. Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics. Fertil Steril. 2003;80(2):320–7. https://doi.org/10.1016/s0015-0282(03)00612-5.

    Article  PubMed  Google Scholar 

  30. Omland AK, Abyholm T, Fedorcsak P, Ertzeid G, Oldereid NB, Bjercke S, et al. Pregnancy outcome after IVF and ICSI in unexplained, endometriosis-associated and tubal factor infertility. Hum Reprod. 2005;20(3):722–7. https://doi.org/10.1093/humrep/deh664.

    Article  PubMed  Google Scholar 

  31. Hull MG, Williams JA, Ray B, McLaughlin EA, Akande VA, Ford WC. The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa. Hum Reprod. 1998;13(7):1825–30. https://doi.org/10.1093/humrep/13.7.1825.

    Article  CAS  PubMed  Google Scholar 

  32. van Rooij IA, Broekmans FJ, Hunault CC, Scheffer GJ, Eijkemans MJ, de Jong FH, et al. Use of ovarian reserve tests for the prediction of ongoing pregnancy in couples with unexplained or mild male infertility. Reprod BioMed Online. 2006;12(2):182–90. https://doi.org/10.1016/s1472-6483(10)60859-0.

    Article  PubMed  Google Scholar 

  33. Ray A, Shah A, Gudi A, Homburg R. Unexplained infertility: an update and review of practice. Reprod BioMed Online. 2012;24(6):591–602. https://doi.org/10.1016/j.rbmo.2012.02.021.

    Article  PubMed  Google Scholar 

  34. Fatini C, Conti L, Turillazzi V, Sticchi E, Romagnuolo I, Milanini MN, et al. Unexplained infertility: association with inherited thrombophilia. Thromb Res. 2012;129(5):e185–8. https://doi.org/10.1016/j.thromres.2012.02.012.

    Article  CAS  PubMed  Google Scholar 

  35. Mansour R, El-Faissal Y, Kamel A, Kamal O, Aboulserour G, Aboulghar M, et al. Increased insulin resistance in men with unexplained infertility. Reprod BioMed Online. 2017;35(5):571–5. https://doi.org/10.1016/j.rbmo.2017.08.020.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Assisted Reproduction Unit, Third Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, 1 Rimini Street, Chaidari, 12642, Athens, Greece

    Charalampos Siristatidis

  2. Assisted Reproducton Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Charalampos Siristatidis

  3. Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, 1 Rimini Street, Chaidari, 12642, Athens, Greece

    Abraham Pouliakis

  4. Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, “Alexandra” Hospital, 80 Vas. Sofias Ave, 11528, Athens, Greece

    Theodoros N. Sergentanis

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  1. Charalampos Siristatidis
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Correspondence to Charalampos Siristatidis.

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Siristatidis, C., Pouliakis, A. & Sergentanis, T.N. Special characteristics, reproductive, and clinical profile of women with unexplained infertility versus other causes of infertility: a comparative study. J Assist Reprod Genet 37, 1923–1930 (2020). https://doi.org/10.1007/s10815-020-01845-z

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