Skip to main content

Advertisement

SpringerLink
Log in

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

  • Original Article
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

Purpose

Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated.

Methods

This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography–mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated.

Results

The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups.

Conclusion

FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

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

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

References

  1. Welshons WV, Nagel SC,vom Saal FS (2006) Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology 147: 6 Suppl: S56–69

  2. Wetherill YB, Akingbemi BT, Kanno J et al (2007) In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol 24(2):178–198

    Article  CAS  PubMed  Google Scholar 

  3. Santangeli S, Maradonna F, Olivotto I et al (2017) Effects of BPA on female reproductive function: the involvement of epigenetic mechanism. Gen Comp Endocrinol 245:122–126

    Article  CAS  PubMed  Google Scholar 

  4. Karrer C, Roiss T, von Goetz N et al (2018) Physiologically Based Pharmacokinetic (PBPK) Modeling of the Bisphenols BPA, BPS, BPF, and BPAF with new experimental metabolic parameters: comparing the pharmacokinetic behavior of BPA with its substitutes. Environ Health Perspect 126: 7: 077002

  5. Machtinger R, Orvieto R (2014) Bisphenol A, oocyte maturation, implantation, and IVF outcome: review of animal and human data. Reprod Biomed Online 29(4):404–410

    Article  CAS  PubMed  Google Scholar 

  6. Zhu X, Tian GG, Yu B et al (2018) Effects of bisphenol A on ovarian follicular development and female germline stem cells. Arch Toxicol 92(4):1581–1591

    Article  CAS  PubMed  Google Scholar 

  7. Patel S, Brehm E, Gao L et al (2017) Bisphenol A exposure, ovarian follicle numbers, and female sex steroid hormone levels: results from a CLARITY-BPA study. Endocrinology 158(6):1727–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tomza-Marciniak A, Stepkowska P, Kuba J et al (2018) Effect of bisphenol A on reproductive processes: a review of in vitro, in vivo and epidemiological studies. J Appl Toxicol 38(1):51–80

    Article  CAS  PubMed  Google Scholar 

  9. Hewlett M, Chow E, Aschengrau A et al (2017) Prenatal exposure to endocrine disruptors: a developmental etiology for polycystic ovary syndrome. Reprod Sci 24(1):19–27

    Article  CAS  PubMed  Google Scholar 

  10. Sugiura-Ogasawara M, Ozaki Y, Sonta S et al (2005) Exposure to bisphenol A is associated with recurrent miscarriage. Hum Reprod 20(8):2325–2329

    Article  CAS  PubMed  Google Scholar 

  11. Beydoun HA, Beydoun MA, Jeng HA et al (2016) Bisphenol-A and sleep adequacy among adults in the national health and nutrition examination surveys. Sleep 39(2):467–476

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ehrlich S, Williams PL, Missmer SA et al (2012) Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF. Hum Reprod 27(12):3583–3592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mok-Lin E, Ehrlich S, Williams PL et al (2010) Urinary bisphenol A concentrations and ovarian response among women undergoing IVF. Int J Androl 33(2):385–393

    Article  CAS  PubMed  Google Scholar 

  14. Minguez-Alarcon L, Gaskins AJ, Chiu YH et al (2015) Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic. Hum Reprod 30(9):2120–2128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Akash MSH, Sabir S,Rehman K (2020) Bisphenol A-induced metabolic disorders: from exposure to mechanism of action. Environ Toxicol Pharmacol 77: 103373

  16. Milanovic M, Milosevic N, Sudji J et al (2020) Can environmental pollutant bisphenol A increase metabolic risk in polycystic ovary syndrome? Clin Chim Acta 507:257–263

    Article  CAS  PubMed  Google Scholar 

  17. Hong SH, Sung YA, Hong YS et al (2017) Urinary bisphenol A is associated with insulin resistance and obesity in reproductive-aged women. Clin Endocrinol (Oxf) 86(4):506–512

    Article  CAS  Google Scholar 

  18. Savastano S, Tarantino G, D’Esposito V et al (2015) Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance: a cross-sectional study on adult male population. J Transl Med 13:169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Soundararajan A, Prabu P, Mohan V et al (2019) Novel insights of elevated systemic levels of bisphenol-A (BPA) linked to poor glycemic control, accelerated cellular senescence and insulin resistance in patients with type 2 diabetes. Mol Cell Biochem 458(1–2):171–183

    Article  CAS  PubMed  Google Scholar 

  20. Kandaraki E, Chatzigeorgiou A, Livadas S et al (2011) Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab 96(3):E480–E484

    Article  CAS  PubMed  Google Scholar 

  21. Kandaraki E, Christakou C,Diamanti-Kandarakis E (2009) Metabolic syndrome and polycystic ovary syndrome... and vice versa. Arq Bras Endocrinol Metabol 53: 2: 227–37

  22. Rotterdam EA-SPcwg, (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19(1):41–47

    Article  Google Scholar 

  23. Dun EC, Nezhat CH (2012) Tubal factor infertility: diagnosis and management in the era of assisted reproductive technology. Obstet Gynecol Clin North Am 39(4):551–566

    Article  PubMed  Google Scholar 

  24. Heijnen EM, Eijkemans MJ, Hughes EG et al (2006) A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update 12(1):13–21

    Article  CAS  PubMed  Google Scholar 

  25. Food and Drug Administration (FDA) CfDEaRC, Center for Veterinary Medicine (CVM), Bioanalytical Method Validation-Guidance for Industry, U.S.D.o.H.a.H. Services, Editor. 2018, Food and Drug Administration (FDA).

  26. Group IEW, Validation of Analytical Procedures: Text and Methodology-Q2(R1), I.C.o.H.o.t.r.f.r.o.p.f.h. use, Editor. 2005.

  27. Asimakopoulos AG, Thomaidis NS, Koupparis MA (2012) Recent trends in biomonitoring of bisphenol A, 4-t-octylphenol, and 4-nonylphenol. Toxicol Lett 210(2):141–154

    Article  CAS  PubMed  Google Scholar 

  28. Ye X, Zhou X, Hennings R et al (2013) Potential external contamination with bisphenol A and other ubiquitous organic environmental chemicals during biomonitoring analysis: an elusive laboratory challenge. Environ Health Perspect 121(3):283–286

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Vandenberg LN, Chahoud I, Heindel JJ et al (2010) Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 118(8):1055–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Esinler I, Bayar U, Bozdag G et al (2005) Outcome of intracytoplasmic sperm injection in patients with polycystic ovary syndrome or isolated polycystic ovaries. Fertil Steril 84(4):932–937

    Article  PubMed  Google Scholar 

  31. Esmailzadeh S, Faramarzi M, Jorsarai G (2005) Comparison of in vitro fertilization outcome in women with and without sonographic evidence of polycystic ovarian morphology. Eur J Obstet Gynecol Reprod Biol 121(1):67–70

    Article  PubMed  Google Scholar 

  32. Wang Y, Zhu Q, Dang X et al (2017) Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS. Gynecol Endocrinol 33(1):21–25

    Article  CAS  PubMed  Google Scholar 

  33. Bloom MS, Mok-Lin E, Fujimoto VY (2016) Bisphenol A and ovarian steroidogenesis. Fertil Steril 106(4):857–863

    Article  CAS  PubMed  Google Scholar 

  34. Mansur A, Adir M, Racowsky C et al (2017) Susceptibility of human cumulus cells to bisphenol a In vitro. Reprod Toxicol 74:189–194

    Article  CAS  PubMed  Google Scholar 

  35. Mansur A, Israel A, Combelles CM et al (2017) Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro. Hum Reprod 32(2):409–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Acuna-Hernandez DG, Arreola-Mendoza L, Santacruz-Marquez R et al (2018) Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex. Toxicol Appl Pharmacol 344:13–22

    Article  CAS  PubMed  Google Scholar 

  37. Hu Y, Wen S, Yuan D et al (2018) The association between the environmental endocrine disruptor bisphenol A and polycystic ovary syndrome: a systematic review and meta-analysis. Gynecol Endocrinol 34(5):370–377

    Article  CAS  PubMed  Google Scholar 

  38. Konieczna A, Rachon D, Owczarek K et al (2018) Serum bisphenol A concentrations correlate with serum testosterone levels in women with polycystic ovary syndrome. Reprod Toxicol 82:32–37

    Article  CAS  PubMed  Google Scholar 

  39. Takeuchi T, Tsutsumi O, Ikezuki Y et al (2004) Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J 51(2):165–169

    Article  CAS  PubMed  Google Scholar 

  40. Vahedi M, Saeedi A, Poorbaghi SL et al (2016) Metabolic and endocrine effects of bisphenol A exposure in market seller women with polycystic ovary syndrome. Environ Sci Pollut Res Int 23(23):23546–23550

    Article  CAS  PubMed  Google Scholar 

  41. Fernandez MF, Arrebola JP, Taoufiki J et al (2007) Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reprod Toxicol 24(2):259–264

    Article  CAS  PubMed  Google Scholar 

  42. Wang L, Asimakopoulos AG, Kannan K (2015) Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic compounds in human adipose tissue. Environ Int 78:45–50

    Article  CAS  PubMed  Google Scholar 

  43. Michalowicz J (2014) Bisphenol A—sources, toxicity and biotransformation. Environ Toxicol Pharmacol 37(2):738–758

    Article  CAS  PubMed  Google Scholar 

  44. Geens T, Neels H, Covaci A (2012) Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose tissue, liver and brain. Chemosphere 87(7):796–802

    Article  CAS  PubMed  Google Scholar 

  45. Takeuchi T, Tsutsumi O, Ikezuki Y et al (2006) Elevated serum bisphenol A levels under hyperandrogenic conditions may be caused by decreased UDP-glucuronosyltransferase activity. Endocr J 53(4):485–491

    Article  CAS  PubMed  Google Scholar 

  46. Yokota H, Iwano H, Endo M et al (1999) Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver. Biochem J 340(Pt 2):405–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Takeuchi T, Tsutsumi O (2002) Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels. Biochem Biophys Res Commun 291(1):76–78

    Article  CAS  PubMed  Google Scholar 

  48. Hossein Rashidi B, Amanlou M, Behrouzi Lak T et al (2017) The association between bisphenol A and polycystic ovarian syndrome: a case-control study. Acta Med Iran 55(12):759–764

    PubMed  Google Scholar 

  49. Lakind JS, Levesque J, Dumas P et al (2012) Comparing United States and Canadian population exposures from National Biomonitoring Surveys: bisphenol A intake as a case study. J Expo Sci Environ Epidemiol 22(3):219–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang Z, Alomirah H, Cho HS et al (2011) Urinary bisphenol A concentrations and their implications for human exposure in several Asian countries. Environ Sci Technol 45(16):7044–7050

    Article  CAS  PubMed  Google Scholar 

  51. Covaci A, Den Hond E, Geens T et al (2015) Urinary BPA measurements in children and mothers from six European member states: overall results and determinants of exposure. Environ Res 141:77–85

    Article  CAS  PubMed  Google Scholar 

  52. Bushnik T, Haines D, Levallois P et al (2010) Lead and bisphenol A concentrations in the Canadian population. Health Rep 21(3):7–18

    PubMed  Google Scholar 

  53. Broekmans FJ, Knauff EA, te Velde ER et al (2007) Female reproductive ageing: current knowledge and future trends. Trends Endocrinol Metab 18(2):58–65

    Article  CAS  PubMed  Google Scholar 

  54. Yding Andersen C, Westergaard LG, Teisner B et al (1992) Changes induced in serum protein profiles by ovarian stimulation during in-vitro fertilization—embryo transfer treatment: a comparison between conception and non-conception cycles. Hum Reprod 7(5):585–591

    Article  CAS  PubMed  Google Scholar 

  55. Lin KC, Sun MJ (2005) Relationship between sex hormone-binding globulin and pregnancy outcome in women undergoing controlled ovarian hyperstimulation for assisted reproduction. Endocr J 52(4):407–412

    Article  CAS  PubMed  Google Scholar 

  56. Thuesen LL, Smitz J, Loft A et al (2013) Endocrine effects of hCG supplementation to recombinant FSH throughout controlled ovarian stimulation for IVF: a dose-response study. Clin Endocrinol (Oxf) 79(5):708–715

    CAS  Google Scholar 

Download references

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Endocrine Unit, Medical School, Aretaieion University Hospital, National and Kapodistrian University of Athens, 76 Vas. Sofias Str, PO Box 11528, Athens, Greece

    Areti Mina, Panagiotis Christopoulos, Eleni Kousta & George Mastorakos

  2. Department of Forensic Medicine and Toxicology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, PO Box 11527, Athens, Greece

    Areti Mina, Ioannis Papoutsis & Sotirios Athanaselis

  3. Endocrine Unit, Department of Pathophysiology, Medical School, Laiko University Hospital, National and Kapodistrian University of Athens, 75 Mikras Asias Str, PO Box 11527, Athens, Greece

    Georgios Boutzios

  4. Hormonal and Biochemical Laboratory, Medical School, Aretaieion University Hospital, National and Kapodistrian University of Athens, 76 Vas. Sofias Str, PO Box 11528, Athens, Greece

    George Kaparos

  5. Embryogenesis Assisted Conception Unit, Kifisias 49 Avenue, PO Box 15123, Athens, Greece

    Minas Mastrominas

Authors
  1. Areti Mina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgios Boutzios
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ioannis Papoutsis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Kaparos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Panagiotis Christopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eleni Kousta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Minas Mastrominas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sotirios Athanaselis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. George Mastorakos
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Areti Mina: data curation; formal analysis; investigation; methodology; project administration; resources; validation; visualization; writing—original draft. Georgios Boutzios: conceptualization; funding acquisition; methodology; project administration; resources; visualization; writing—review and editing. Ioannis Papoutsis: data curation; investigation; methodology; project administration; resources; validation; writing—review and editing. George Kaparos: investigation; validation; writing—review and editing. Panagiotis Christopoulos: conceptualization; methodology; writing—review and editing. Eleni Kousta: conceptualization; methodology; writing—review and editing. Minas Mastrominas: Investigation; resources; writing—review and editing. Sotirios Athanaselis: methodology; resources; supervision; validation; visualization; writing—review and editing. George Mastorakos: conceptualization; funding acquisition; methodology; supervision; visualization; writing—review and editing. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to George Mastorakos.

Ethics declarations

Ethics approval

The study was approved by the Bioethical Committee of our Institution. All procedures performed in this study were in accordance with the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Written informed consent was obtained from all participants included in this study.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Additional informed consent was obtained from all individual participants for whom identifying information is included in this study.

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Areti Mina and Georgios Boutzios should be considered joint first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mina, A., Boutzios, G., Papoutsis, I. et al. Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility. Hormones 21, 305–315 (2022). https://doi.org/10.1007/s42000-022-00370-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-022-00370-1

Keywords

Search

Navigation