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Licensed Unlicensed Requires Authentication Published by De Gruyter January 17, 2015

Development of the first urinary reproductive hormone ranges referenced to independently determined ovulation day

  • Sarah Johnson EMAIL logo , Sarah Weddell , Sonya Godbert , Guenter Freundl , Judith Roos and Christian Gnoth

Abstract

Background: Urinary hormone level analysis provides valuable fertility status information; however, previous studies have not referenced levels to the ovulation day, or have used outdated methods. This study aimed to produce reproductive hormone ranges referenced to ovulation day determined by ultrasound.

Methods: Women aged 18–40 years (no reported infertility) collected daily urine samples for one complete menstrual cycle. Urinary luteinising hormone (LH), estrone-3-glucuronide (E3G, an estradiol metabolite), follicle stimulating hormone (FSH) and pregnanediol-3-glucuronide (P3G, a progesterone metabolite) were measured using previously validated assays. Volunteers underwent trans-vaginal ultrasound every 2 days until the dominant ovarian follicle size reached 16 mm, when daily scans were performed until ovulation was observed. Data were analysed to create hormone ranges referenced to the day of objective ovulation as determined by ultrasound.

Results: In 40 volunteers, mean age 28.9 years, urinary LH surge always preceded ovulation with a mean of 0.81 days; thus LH is an excellent assay-independent predictor of ovulation. The timing of peak LH was assay-dependent and could be post-ovulatory; therefore should no longer be used to predict/determine ovulation. Urinary P3G rose from baseline after ovulation in all volunteers, peaking a median of 7.5 days following ovulation. Median urinary peak E3G and FSH levels occurred 0.5 days prior to ovulation. A persistent rise in urinary E3G was observed from approximately 3 days pre- until 5 days post-ovulation.

Conclusions: This study provides reproductive hormone ranges referenced to the actual day of ovulation as determined by ultrasound, to facilitate examination of menstrual cycle endocrinology.


Corresponding author: Sarah Johnson, Head of Regulatory and Clinical Affairs, SPD Development Co., Ltd, Priory Business Park, Bedford, MK44 3UP, UK, Phone: +44 1234 835 486, Fax: +44 1234 835 006, E-mail:

Acknowledgments

Editorial support for the development of this manuscript was provided by Dr. Debra Scates from IMC Healthcare Communication, sponsored by SPD Development Co., Ltd.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: This study was funded by SPD Development Co., Ltd., a wholly-owned subsidiary of SPD Swiss Precision Diagnostics GmbH. Trial registration number: NCT01802060.

Employment or leadership: S. Johnson, S. Weddell and S. Godbert are employees of SPD Development Co., Ltd. G. Freundl has received consultancy from SPD Development Co., Ltd.

Honorarium: None declared.

Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Balasch J, Gratacós E. Delayed childbearing: effects on fertility and the outcome of pregnancy. Fetal Diagn Ther 2011;29:263–73.10.1159/000323142Search in Google Scholar PubMed

2. Heffner LJ. Advanced maternal age – how old is too old? N Engl J Med 2004;351:1924–9.10.1056/NEJMp048087Search in Google Scholar PubMed

3. Committee opinion No. 589. Female age-related fertility decline. Fertil Steril 2014;101:633–4.10.1016/j.fertnstert.2013.12.032Search in Google Scholar PubMed

4. Lundsberg LS, Pal L, Gariepy AM, Xu X, Chu MC, Illuzzi LJ. Knowledge, attitudes, and practices regarding conception and fertility: a population-based survey among reproductive-age United States women. Fertil Steril 2014;101:767–74.10.1016/j.fertnstert.2013.12.006Search in Google Scholar PubMed

5. Gnoth C, Frank-Herrmann P, Schmoll A, Godehardt E, Freundl G. Cycle characteristics after discontinuation of oral contraceptives. Gynecol Endocrinol 2002;16:307–17.10.1080/gye.16.4.307.317Search in Google Scholar

6. Zinaman M, Johnson S, Ellis J, Ledger W. Accuracy of perception of ovulation day in women trying to conceive. CMRO 2012;28:1–6.10.1185/03007995.2012.681638Search in Google Scholar PubMed

7. Johnson SR, Miro F, Barrett S, Ellis J. Levels of urinary human chorionic gonadotrophin (hCG) following conception and variability of the menstrual cycle in a cohort of women attempting to conceive. CMRO 2009;25:741–8.10.1185/03007990902743935Search in Google Scholar PubMed

8. Creinin MD, Keverline S, Meyn LA. How regular is regular? An analysis of menstrual cycle regularity. Contraception 2004;70:289–92.10.1016/j.contraception.2004.04.012Search in Google Scholar PubMed

9. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. N Engl J Med 1995;333:1517–21.10.1056/NEJM199512073332301Search in Google Scholar PubMed

10. Liu Y, Johnson WO, Gold EB, Lasley BL. Bayesian analysis of risk factors for anovulation. Stat Med 2004;23:1901–19.10.1002/sim.1773Search in Google Scholar PubMed

11. Hambridge H, Mumford SL, Mattison DR, Ye A, Pollack AZ, Bloom MS, et al. The influence of sporadic anovulation on hormone levels in ovulatory cycles. Hum Reprod 2013;28:1687–94.10.1093/humrep/det090Search in Google Scholar

12. Collins WP. The evolution of reference methods to monitor ovulation. Am J Obstet Gynecol 1991;165:1994–6.10.1016/S0002-9378(11)90564-XSearch in Google Scholar

13. Kassam A, Overstreet JW, Snow-Harter C, De Souza MJ, Gold EB, Lasley BL. Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm. Environ Health Perspect 1996;104:408–13.10.1289/ehp.96104408Search in Google Scholar

14. Blackwell LF, Vigil P, Cooke DG, d’Arcangues C, Brown JB. Monitoring of ovarian activity by daily measurement of urinary excretion rates of oestrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part III: variability of normal menstrual cycle profiles. Hum Reprod 2013;28:3306–15.10.1093/humrep/det389Search in Google Scholar

15. Stricker R, Eberhart R, Chevailler M, Quinn F, Bischof P, Stricker R. Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyser. Clin Chem Lab Med 2006;44:883–7.10.1515/CCLM.2006.160Search in Google Scholar

16. Seibel M. Luteinizing hormone and ovulation timing. J Reprod Med 1986;31:754–9.Search in Google Scholar

17. Direito A, Bailly S, Mariani A, Ecochard R. Relationships between the luteinizing hormone surge and other characteristics of the menstrual cycle in normally ovulating women. Fertil Steril 2013;99:279–85.10.1016/j.fertnstert.2012.08.047Search in Google Scholar

18. Ecochard R, Leiva R, Bouchard T, Boehringer H, Direito A, Mariani A, et al. Use of urinary pregnanediol 3-glucuronide to confirm ovulation. Steroids 2013;78:1035–40.10.1016/j.steroids.2013.06.006Search in Google Scholar

19. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. On behalf of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011;377:557–67.10.1016/S0140-6736(10)62037-5Search in Google Scholar

20. Hahn KA, Wise LA, Riis AH, Mikkelsen EM, Rothman KJ, Banholzer K, et al. Correlates of menstrual cycle characteristics among nulliparous Danish women. Clin Epidemiol 2013;5:311–9.10.2147/CLEP.S46712Search in Google Scholar PubMed PubMed Central

21. Kerin JF, Edmonds D, Warnes G, Cox L, Seamark R, Mathews C, et al. Morphological and functional relations of Graafian follicle growth to ovulation in women using ultrasonic, laparoscopic and biochemical measurements. Br J Obstet Gynecol 1981;88:81–90.10.1111/j.1471-0528.1981.tb00947.xSearch in Google Scholar PubMed

22. Neven P, Iles RK, Howes I, Sharma K, Shepherd JH, Edwards R, et al. Substantial urinary concentrations of material resembling β-core fragment of chorionic gonadrotropin β-subunit in mid-menstrual cycle. Clin Chem 1993;39:1857–60.10.1093/clinchem/39.9.1857Search in Google Scholar

23. O’Connor JF, Kovalevskaya G, Birken S, Schlatterer JP, Schechter D, McMahon DJ, et al. The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay. Hum Reprod 1998;13:826–35.10.1093/humrep/13.4.826Search in Google Scholar

24. Kurowska E, Szewczuk A. Isolation of human lutropin from woman urine and comparison of its properties with pituitary hormone. Arch Immunol Ther Exp 1999;47:179–83.Search in Google Scholar

25. Birken S, Gawinowiz MA, Maydelman Y, Migrom Y. Metabolism of gonadotropins: comparison of the primary structures of the human pituitary and urinary LHβ cores and the chimpanzee CGβ core demonstrates universality of core production. J Endocrinol 2001;171:131–41.10.1677/joe.0.1710131Search in Google Scholar

26. Park SJ, Goldsmith LT, Skurnick JH, Wojtczuk A, Weiss G. Characteristics of the urinary luteinizing hormone surge in young ovulatory women. Fert Steril 2007;88:684–90.10.1016/j.fertnstert.2007.01.045Search in Google Scholar

27. Ecochard R, Boehringer H, Rabilloud M, Marret H. Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation. Br J Obstet Gynecol 2001;108:822–9.Search in Google Scholar

28. Elkind-Hirsch K, Goldzieher JW, Gibbons WE, Besch PK. Evaluation of the Ovustick urinary luteinizing hormone kit in normal and stimulated menstrual cycles. Obstet Gynecol 1986;67:450–3.Search in Google Scholar

29. Gudgeon K, Leader L, Howard B. Evaluation of the accuracy of the home ovulation detection kit, Clearplan, at predicting ovulation. Med J Aust 1990;152:345–9.10.5694/j.1326-5377.1990.tb125181.xSearch in Google Scholar

30. Guermandi E, Vegetti W, Bianchi MM, Uglietti A, Ragni G, Crosignani P. Reliability of ovulation tests in infertile women. Obstet Gynecol 2001;97:92–6.Search in Google Scholar

31. Leiva R, Burhan U, Kyrillos E, Fehring R, McLaren R, Dalzell C, et al. Use of ovulation predictor kits as adjuncts when using fertility awareness methods (FAMs): a pilot study. J Am Board Fam Med 2014;27:427–9.10.3122/jabfm.2014.03.130255Search in Google Scholar

32. Miller PB, Soules MR. Ovulation prediction during menstrual cycles of normal women. Obstet Gynecol 1996;87:13–7.10.1016/0029-7844(95)00352-5Search in Google Scholar

33. Cervinski MA, Gronowski AM. Reproductive-endocrine point-of-care testing: current status and limitations. Clin Chem Lab Med 2010;48:935–42.Search in Google Scholar

34. Behre HM, Kuhlage J, Gassner C, Sonntage B, Schem C, Schneider HP, et al. Prediction of ovulation by urinary hormone measurements with the home use Clearblue Fertility Monitor: comparison with transvaginal ultrasound scans and serum hormone measurements. Hum Reprod 2000;12:2478–82.10.1093/humrep/15.12.2478Search in Google Scholar PubMed

35. Robinson J, Wakelin M, Ellis J. Increased pregnancy rate with use of Clearblue Easy Fertility Monitor. Fertil Steril 2007;87:329–34.10.1016/j.fertnstert.2006.05.054Search in Google Scholar PubMed

36. Gronowski AM, Grenache DG, Markenson G, Weiner R, Demers LM, St. Louis P. Evidence-based practice for point-of-care testing. In: Nichols JH, editor. Reproductive testing. Washington, DC: American Association for Clinical Chemistry (AACC) Press, 2006.Search in Google Scholar

37. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85:2434–8.10.1210/jc.85.7.2434Search in Google Scholar

38. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745–9.10.1210/jc.2003-032046Search in Google Scholar PubMed

39. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999;84:4006–11.10.1210/jcem.84.11.6148Search in Google Scholar PubMed

40. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998;83:3078–82.10.1210/jc.83.9.3078Search in Google Scholar

41. Miro F, Coley J, Gani MM, Perry PW, Talbot D, Aspinall LJ. Comparison between creatinine and pregnanediol adjustments in the retrospective analysis of urinary hormone profiles during the human menstrual cycle. Clin Chem Lab Med 2004;42:1043–50.10.1515/CCLM.2004.210Search in Google Scholar PubMed

42. Zacur H, Kaufman SC, Smith B, Wshoff C, Helbig D, Lee YJ, et al. Does creatinine adjustment of urinary pregnanediol glucuronide reduce or introduce measurement error? Gynecol Endocrinol 1997;11:29–33.10.3109/09513599709152314Search in Google Scholar PubMed

43. Marsh EE, Shaw ND, Klingman KM, Tiamfook-Morgan TO, Yialamas MA, Sluss PM, et al. Estrogen levels are higher across the menstrual cycle in African-American women compared with Caucasian women. J Clin Endocrinol Metab 2011;96:3199–206.10.1210/jc.2011-1314Search in Google Scholar PubMed PubMed Central

Received: 2014-11-5
Accepted: 2014-12-11
Published Online: 2015-1-17
Published in Print: 2015-6-1

©2015 by De Gruyter

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