Skip to main content
SpringerLink
Log in

May Underdiagnosed Nutrition Imbalances Be Responsible for a Portion of So-Called Unexplained Infertility? From Diagnosis to Potential Treatment Options

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The aim of the study was to investigate whether women affected by unexplained infertility may have undiagnosed dietary imbalances which negatively affect fertility. Secondarily, we investigated whether varying degrees of nutritional abnormalities may benefit from different periconceptional dietary supplementations, evaluating the most effective intervention in improving pregnancy rate after in vitro fertilization (IVF). We conducted a survey on 2 cohorts of patients (group A: unexplained infertility and group B: healthy first trimester spontaneous pregnancies) with the scope of investigating and comparing their dietary status discriminating women without dietary abnormalities (cohort 1) from those with abnormalities exclusively in micronutrient intake (cohort 2) or combined abnormalities in both micronutrient and macronutrient intake and associated obesity (cohort 3). All women included in group A were offered the opportunity to receive a prescription for one of the 3 designated daily dietary supplementation schemes (subgroups A1, A2, and A3) which were to be implemented in the 3 months immediately prior to beginning IVF treatment. When compared with fertile women, patients having unexplained infertility showed significant abnormalities in dietary habits. These differences ranged from a minimal imbalance in micronutrient intake (potentially avoidable with dietary supplementation) to severe combined macronutrient and micronutrient imbalance frequently associated with obesity (partially amendable by inositol supplementation and frequently requiring long-term dietary reeducation before establishment of fertility). Nutritional investigation and treatment may explain and resolve a portion of cases of unexplained infertility, improving the outcome of IVF treatment and, with minimal imbalances, likely restore spontaneous fertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gizzo S, Andrisani A, Esposito F, et al. Ovarian reserve test: an impartial means to resolve the mismatch between chronological and biological age in the assessment of female reproductive chances. Reprod Sci. 2014;21(5):632–639.

    PubMed  Google Scholar 

  2. Sadeghi MR. Unexplained infertility, the controversial matter in management of infertile couples. J Reprod Infertil. 2015; 16(1):1–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Gelbaya TA, Potdar N, Jeve YB, Nardo LG. Definition and epidemiology of unexplained infertility. Obstet Gynecol Surv. 2014; 69(2):109–115.

    PubMed  Google Scholar 

  4. Nardelli AA, Stafinski T, Motan T, Klein K, Menon D. Assisted reproductive technologies (ARTs): evaluation of evidence to support public policy development. Reprod Health. 2014; 11(1):76.

    PubMed  PubMed Central  Google Scholar 

  5. Twigt JM, Bolhuis ME, Steegers EA, et al. The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment. Hum Reprod. 2012;27(8): 2526–2531.

    CAS  PubMed  Google Scholar 

  6. Román-Viñas B, Serra-Majem L, Ribas-Barba L, et al. Overview of methods used to evaluate the adequacy of nutrient intakes for individuals and populations. Br J Nutr. 2009;101(suppl 2):s6–s11.

    PubMed  Google Scholar 

  7. Patrelli TS, Berretta R, Gizzo S, et al. CA 125 serum values in surgically treated endometriosis patients and its relationships with anatomic sites of endometriosis and pregnancy rate. Fertil Steril. 2011;95(1):393–396.

    CAS  PubMed  Google Scholar 

  8. Gizzo S, Patrelli TS, Rossanese M, et al. An update on diabetic women obstetrical outcomes linked to preconception and pregnancy glycemic profile: a systematic literature review. Scientific-WorldJournal. 2013;2013:254901

    PubMed  PubMed Central  Google Scholar 

  9. Saccardi C, Conte L, Fabris A, et al. Hysteroscopic enucleation in toto of submucous type 2 myomas: long-term follow-up in women affected by menorrhagia. Minim Invasive Gynecol. 2014;21(3): 426–430.

    Google Scholar 

  10. Litta P, Cosmi E, Saccardi C, Esposito C, Rui R, Ambrosini G. Outpatient operative polypectomy using a 5 mm-hysteroscope without anaesthesia and/or analgesia: advantages and limits. Eur J Obstet Gynecol Reprod Biol. 2008;139(2):210–214.

    PubMed  Google Scholar 

  11. Gizzo S, Capuzzo D, Zicchina C, et al. Could empirical low-dose-aspirin administration during IVF cycle affect both the oocytes and embryos quality via COX 1–2 activity inhibition? J Assist Reprod Genet. 2014;31(3):261–268.

    PubMed  PubMed Central  Google Scholar 

  12. Patrelli TS, Dall’asta A, Gizzo S, et al. Calcium supplementation and prevention of preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med. 2012;25(12):2570–2574.

    CAS  PubMed  Google Scholar 

  13. LARN – Livelli di Assunzione di Riferimento di Nutrienti ed energia per la popolazione italiana, Revisione 2012. Documento di sintesi per il XXXV Congresso Nazionale SINU. 2012. Web site. http://www.sinu.it/html/pag/nuovi_larn.asp.

  14. Neuber E, Rinaudo P, Trimarchi JR, Sakkas D. Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development. Hum Reprod. 2003;18(6):1307–1312

    CAS  Google Scholar 

  15. Gizzo S, Andrisani A, Esposito F, et al. Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial. Gynecol Endocrinol. 2014;30:1–7.

    Google Scholar 

  16. Nazni P. Association of western diet & lifestyle with decreased fertility. Indian J Med Res. 2014;140 suppl:s78–s81.

    PubMed  PubMed Central  Google Scholar 

  17. ESHRE Capri Workshop Group. Nutrition and reproduction in women. Hum Reprod Update. 2006;12(3):193–207.

    Google Scholar 

  18. Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29(4):498–506. pii:s1521– s6934(14)00241–7.

    PubMed  Google Scholar 

  19. Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online. 2007;15(5):532–538.

    CAS  PubMed  Google Scholar 

  20. Unfer V, Carlomagno G, Dante G, Facchinetti F. Effects of myoinositol in women with PCOS: a systematic review of randomized controlled trials. Gynecol Endocrinol. 2012;28(7):509–515.

    CAS  PubMed  Google Scholar 

  21. Vitagliano A, Quaranta M, Noventa M, Gizzo S. ‘‘Empiric’’ inositol supplementation in normal-weight non insulin resistant women with polycystic ovarian disease: from the absence of benefit to the potential adverse effects. Arch Gynecol Obstet. 2015; 291(5):955–957.

    PubMed  Google Scholar 

  22. Kasim-Karakas SE, Cunningham WM, Tsodikov A. Relation of nutrients and hormones in polycystic ovary syndrome. Am J Clin Nutr. 2007;85(3):688–694.

    CAS  PubMed  Google Scholar 

  23. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility. Eur J Clin Nutr. 2009; 63(1):78–86.

    CAS  PubMed  Google Scholar 

  24. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Dietary fatty acid intakes and the risk of ovulatory infertility. Am J Clin Nutr. 2007;85(1):231–237.

    CAS  PubMed  Google Scholar 

  25. Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3(3):397–403.

    CAS  PubMed  Google Scholar 

  26. Chakraborty P, Ghosh S, Goswami SK, Kabir SN, Chakravarty B, Jana K. Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res. 2013;152(1):9–15.

    CAS  PubMed  Google Scholar 

  27. Cetin I, Berti C, Calabrese S. Role of micronutrients in the periconceptional period. Hum Reprod Update. 2010;16(1):80–95.

    CAS  PubMed  Google Scholar 

  28. Agrawal R, Burt E, Gallagher AM, Butler L, Venkatakrishnan R, Peitsidis P. Prospective randomized trial of multiple micronutrients in subfertile women undergoing ovulation induction: a pilot study. Reprod Biomed Online. 2012;24(1):54–60.

    CAS  PubMed  Google Scholar 

  29. Altmäe S, Stavreus-Evers A, Ruiz JR, et al. Variations in folate pathway genes are associated with unexplained female infertility. Fertil Steril. 2010;94(1):130–137.

    PubMed  Google Scholar 

  30. Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril. 2014;102(2):460–468.

    CAS  PubMed  Google Scholar 

  31. Ruder EH, Hartman TJ, Reindollar RH, Goldman MB. Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility. Fertil Steril. 2014;101(3): 759–766.

    CAS  PubMed  Google Scholar 

  32. Gizzo S, Noventa M, Di Gangi S, et al. Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale. Clin Chem Lab Med. 2015;53(7):975–979.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Woman and Child Health, University of Padua, Padua, Italy

    Marco Noventa MD, Amerigo Vitagliano MD, Vescio Cinthya, Michele Gangemi MD, Carlo Saccardi MD, PhD, Giovanni Battista Nardelli MD & Salvatore Gizzo MD

  2. Department of Obstetrics and Gynaecology, University of Verona, Verona, Italy

    Michela Quaranta MD & Rossana Di Paola MD

  3. Department of Medicine, University of Padua, Padua, Italy

    Romina Valentini & Tania Campagnaro

  4. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

    Roberto Marci MD

  5. Department of Neurosciences and Reproductive Science, University Federico II of Naples, Naples, Italy

    Carlo Alviggi MD, PhD

Authors
  1. Marco Noventa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michela Quaranta MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amerigo Vitagliano MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vescio Cinthya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Romina Valentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tania Campagnaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roberto Marci MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rossana Di Paola MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carlo Alviggi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michele Gangemi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carlo Saccardi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giovanni Battista Nardelli MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Salvatore Gizzo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salvatore Gizzo MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noventa, M., Quaranta, M., Vitagliano, A. et al. May Underdiagnosed Nutrition Imbalances Be Responsible for a Portion of So-Called Unexplained Infertility? From Diagnosis to Potential Treatment Options. Reprod. Sci. 23, 812–822 (2016). https://doi.org/10.1177/1933719115620496

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719115620496

Keywords

Search

Navigation