UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

Evaluation of female infertility

Authors
Wendy Kuohung, MD
Mark D Hornstein, MD
Section Editors
Robert L Barbieri, MD
Deborah Levine, MD
Deputy Editor
Kristen Eckler, MD, FACOG

INTRODUCTION

An infertility evaluation is usually initiated after one year of regular unprotected intercourse in women under age 35 years and after six months of unprotected intercourse in women age 35 years and older. However, the evaluation may be initiated sooner in women with irregular menstrual cycles or known risk factors for infertility, such as endometriosis, a history of pelvic inflammatory disease, or reproductive tract malformations.

The basic evaluation can be performed by an interested and experienced primary care physician or an obstetrician-gynecologist. The primary care physician generally should refer the patient to a specialist for treatment of infertility. Many gynecologists initiate treatment prior to referral to a reproductive endocrinologist. This decision depends upon the results of infertility tests and clinician experience.

Multiple tests have been proposed for evaluation of female infertility. Some of these tests are supported by good evidence, while others are not. This topic will provide an evidence-based approach to the evaluation of female infertility. The etiology and treatment of female infertility, as well as the etiology, evaluation, and treatment of male infertility, are discussed separately.

(See "Overview of infertility".)

(See "Causes of female infertility".)

                           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jun 2015. | This topic last updated: Apr 21, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
References
Top
  1. Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril 2012; 98:302.
  2. Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol 2007; 21:293.
  3. Lass A. The fertility potential of women with a single ovary. Hum Reprod Update 1999; 5:546.
  4. World Health Organization, WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th edition. Cambridge University Press, Cambridge, UK, 1999.
  5. Wathen NC, Perry L, Lilford RJ, Chard T. Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range. Br Med J (Clin Res Ed) 1984; 288:7.
  6. Ecochard R, Boehringer H, Rabilloud M, Marret H. Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation. BJOG 2001; 108:822.
  7. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril 2015; 103:e9.
  8. Committee on Gynecologic Practice. Committee opinion no. 618: Ovarian reserve testing. Obstet Gynecol 2015; 125:268.
  9. Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update 2014; 20:688.
  10. Abdalla H, Thum MY. An elevated basal FSH reflects a quantitative rather than qualitative decline of the ovarian reserve. Hum Reprod 2004; 19:893.
  11. Jain T, Soules MR, Collins JA. Comparison of basal follicle-stimulating hormone versus the clomiphene citrate challenge test for ovarian reserve screening. Fertil Steril 2004; 82:180.
  12. Hendriks DJ, Mol BW, Bancsi LF, et al. The clomiphene citrate challenge test for the prediction of poor ovarian response and nonpregnancy in patients undergoing in vitro fertilization: a systematic review. Fertil Steril 2006; 86:807.
  13. Broekmans FJ, Kwee J, Hendriks DJ, et al. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update 2006; 12:685.
  14. Licciardi FL, Liu HC, Rosenwaks Z. Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril 1995; 64:991.
  15. Smotrich DB, Widra EA, Gindoff PR, et al. Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril 1995; 64:1136.
  16. Souter I, Dimitriadis I, Baltagi LM, et al. Elevated day 3 follicle-stimulating hormone in younger women: is gonadotropin stimulation/intrauterine insemination a good option? Am J Obstet Gynecol 2014; 211:62.e1.
  17. Haadsma ML, Bukman A, Groen H, et al. The number of small antral follicles (2-6 mm) determines the outcome of endocrine ovarian reserve tests in a subfertile population. Hum Reprod 2007; 22:1925.
  18. Deb S, Campbell BK, Clewes JS, Raine-Fenning NJ. Quantitative analysis of antral follicle number and size: a comparison of two-dimensional and automated three-dimensional ultrasound techniques. Ultrasound Obstet Gynecol 2010; 35:354.
  19. Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod 1997; 12:220.
  20. Chang MY, Chiang CH, Hsieh TT, et al. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil Steril 1998; 69:505.
  21. Broekmans FJ, de Ziegler D, Howles CM, et al. The antral follicle count: practical recommendations for better standardization. Fertil Steril 2010; 94:1044.
  22. Jayaprakasan K, Chan Y, Islam R, et al. Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women. Fertil Steril 2012; 98:657.
  23. Rombauts L, Onwude JL, Chew HW, Vollenhoven BJ. The predictive value of antral follicle count remains unchanged across the menstrual cycle. Fertil Steril 2011; 96:1514.
  24. Hsu A, Arny M, Knee AB, et al. Antral follicle count in clinical practice: analyzing clinical relevance. Fertil Steril 2011; 95:474.
  25. Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update 2014; 20:370.
  26. Seifer DB, Baker VL, Leader B. Age-specific serum anti-Müllerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril 2011; 95:747.
  27. de Vet A, Laven JS, de Jong FH, et al. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 2002; 77:357.
  28. Lutchman Singh K, Muttukrishna S, Stein RC, et al. Predictors of ovarian reserve in young women with breast cancer. Br J Cancer 2007; 96:1808.
  29. Nardo LG, Gelbaya TA, Wilkinson H, et al. Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization. Fertil Steril 2009; 92:1586.
  30. Anckaert E, Smitz J, Schiettecatte J, et al. The value of anti-Mullerian hormone measurement in the long GnRH agonist protocol: association with ovarian response and gonadotrophin-dose adjustments. Hum Reprod 2012; 27:1829.
  31. Broer SL, Dólleman M, Opmeer BC, et al. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update 2011; 17:46.
  32. Iliodromiti S, Kelsey TW, Wu O, et al. The predictive accuracy of anti-Müllerian hormone for live birth after assisted conception: a systematic review and meta-analysis of the literature. Hum Reprod Update 2014; 20:560.
  33. Gnoth C, Schuring AN, Friol K, et al. Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod 2008; 23:1359.
  34. van Rooij IA, Broekmans FJ, Scheffer GJ, et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005; 83:979.
  35. Steiner AZ, Herring AH, Kesner JS, et al. Antimüllerian hormone as a predictor of natural fecundability in women aged 30-42 years. Obstet Gynecol 2011; 117:798.
  36. Almog B, Shehata F, Suissa S, et al. Age-related normograms of serum antimüllerian hormone levels in a population of infertile women: a multicenter study. Fertil Steril 2011; 95:2359.
  37. Weghofer A, Dietrich W, Barad DH, Gleicher N. Live birth chances in women with extremely low-serum anti-Mullerian hormone levels. Hum Reprod 2011; 26:1905.
  38. Nelson SM, Iliodromiti S, Fleming R, et al. Reference range for the antimüllerian hormone Generation II assay: a population study of 10,984 women, with comparison to the established Diagnostics Systems Laboratory nomogram. Fertil Steril 2014; 101:523.
  39. Rustamov O, Smith A, Roberts SA, et al. Anti-Mullerian hormone: poor assay reproducibility in a large cohort of subjects suggests sample instability. Hum Reprod 2012; 27:3085.
  40. Su HI, Sammel MD, Homer MV, et al. Comparability of antimüllerian hormone levels among commercially available immunoassays. Fertil Steril 2014; 101:1766.
  41. Toner JP, Seifer DB. Why we may abandon basal follicle-stimulating hormone testing: a sea change in determining ovarian reserve using antimüllerian hormone. Fertil Steril 2013; 99:1825.
  42. Dorgan JF, Spittle CS, Egleston BL, et al. Assay reproducibility and within-person variation of Müllerian inhibiting substance. Fertil Steril 2010; 94:301.
  43. Fleming, R, Deshpande, N, Traynor, I, Yates, RW. Dynamics of FSH-induced follicular growth in subfertile women. Hum Reprod 2006.
  44. Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Müllerian hormone: a new marker for ovarian function. Reproduction 2006; 131:1.
  45. Johnson NP, Bagrie EM, Coomarasamy A, et al. Ovarian reserve tests for predicting fertility outcomes for assisted reproductive technology: the International Systematic Collaboration of Ovarian Reserve Evaluation protocol for a systematic review of ovarian reserve test accuracy. BJOG 2006; 113:1472.
  46. Luttjeboer F, Harada T, Hughes E, et al. Tubal flushing for subfertility. Cochrane Database Syst Rev 2007; :CD003718.
  47. Lim CP, Hasafa Z, Bhattacharya S, Maheshwari A. Should a hysterosalpingogram be a first-line investigation to diagnose female tubal subfertility in the modern subfertility workup? Hum Reprod 2011; 26:967.
  48. Swart P, Mol BW, van der Veen F, et al. The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta-analysis. Fertil Steril 1995; 64:486.
  49. Papaioannou S, Bourdrez P, Varma R, et al. Tubal evaluation in the investigation of subfertility: a structured comparison of tests. BJOG 2004; 111:1313.
  50. Thomas K, Coughlin L, Mannion PT, Haddad NG. The value of Chlamydia trachomatis antibody testing as part of routine infertility investigations. Hum Reprod 2000; 15:1079.
  51. Dabekausen YA, Evers JL, Land JA, Stals FS. Chlamydia trachomatis antibody testing is more accurate than hysterosalpingography in predicting tubal factor infertility. Fertil Steril 1994; 61:833.
  52. Hubacher D, Lara-Ricalde R, Taylor DJ, et al. Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women. N Engl J Med 2001; 345:561.
  53. Veenemans LM, van der Linden PJ. The value of Chlamydia trachomatis antibody testing in predicting tubal factor infertility. Hum Reprod 2002; 17:695.
  54. Mol BW, Dijkman B, Wertheim P, et al. The accuracy of serum chlamydial antibodies in the diagnosis of tubal pathology: a meta-analysis. Fertil Steril 1997; 67:1031.
  55. Rodgers AK, Budrys NM, Gong S, et al. Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility. Fertil Steril 2011; 96:715.
  56. Fiddelers AA, Land JA, Voss G, et al. Cost-effectiveness of Chlamydia antibody tests in subfertile women. Hum Reprod 2005; 20:425.
  57. den Hartog JE, Morré SA, Land JA. Chlamydia trachomatis-associated tubal factor subfertility: Immunogenetic aspects and serological screening. Hum Reprod Update 2006; 12:719.
  58. Mol BW, Collins JA, Van Der Veen F, Bossuyt PM. Cost-effectiveness of hysterosalpingography, laparoscopy, and Chlamydia antibody testing in subfertile couples. Fertil Steril 2001; 75:571.
  59. Land JA, Gijsen AP, Kessels AG, et al. Performance of five serological chlamydia antibody tests in subfertile women. Hum Reprod 2003; 18:2621.
  60. Saunders RD, Shwayder JM, Nakajima ST. Current methods of tubal patency assessment. Fertil Steril 2011; 95:2171.
  61. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril 2000; 73:406.
  62. Balasch J. Investigation of the infertile couple: investigation of the infertile couple in the era of assisted reproductive technology: a time for reappraisal. Hum Reprod 2000; 15:2251.
  63. Smith S, Pfeifer SM, Collins JA. Diagnosis and management of female infertility. JAMA 2003; 290:1767.
  64. Luttjeboer FY, Verhoeve HR, van Dessel HJ, et al. The value of medical history taking as risk indicator for tuboperitoneal pathology: a systematic review. BJOG 2009; 116:612.
  65. Perquin DA, Dörr PJ, de Craen AJ, Helmerhorst FM. Routine use of hysterosalpingography prior to laparoscopy in the fertility workup: a multicentre randomized controlled trial. Hum Reprod 2006; 21:1227.
  66. Oei SG, Helmerhorst FM, Keirse MJ. When is the post-coital test normal? A critical appraisal. Hum Reprod 1995; 10:1711.
  67. Griffith CS, Grimes DA. The validity of the postcoital test. Am J Obstet Gynecol 1990; 162:615.
  68. Collins JA, So Y, Wilson EH, et al. The postcoital test as a predictor of pregnancy among 355 infertile couples. Fertil Steril 1984; 41:703.
  69. Glatstein IZ, Best CL, Palumbo A, et al. The reproducibility of the postcoital test: a prospective study. Obstet Gynecol 1995; 85:396.
  70. Oei SG, Helmerhorst FM, Bloemenkamp KW, et al. Effectiveness of the postcoital test: randomised controlled trial. BMJ 1998; 317:502.
  71. Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertil Steril 2015; 103:e27.
  72. Balasch J, Fábregues F, Creus M, Vanrell JA. The usefulness of endometrial biopsy for luteal phase evaluation in infertility. Hum Reprod 1992; 7:973.
  73. Edwards RG. Physiological and molecular aspects of human implantation. Hum Reprod 1995; 10 Suppl 2:1.
  74. Creus M, Balasch J, Ordi J, et al. Integrin expression in normal and out-of-phase endometria. Hum Reprod 1998; 13:3460.
  75. Giudice LC. Potential biochemical markers of uterine receptivity. Hum Reprod 1999; 14 Suppl 2:3.
  76. Murray MJ, Meyer WR, Zaino RJ, et al. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 2004; 81:1333.
  77. Davis OK, Berkeley AS, Naus GJ, et al. The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies. Fertil Steril 1989; 51:582.
  78. Coutifaris C, Myers ER, Guzick DS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004; 82:1264.
  79. Bauman JE. Basal body temperature: unreliable method of ovulation detection. Fertil Steril 1981; 36:729.
  80. Kambic R, Gray RH. Interobserver variation in estimation of day of conception intercourse using selected natural family planning charts. Fertil Steril 1989; 51:430.
  81. Shibahara H, Mitsuo M, Inoue M, et al. Relationship between human in-vitro fertilization and intracytoplasmic sperm injection and the zona-free hamster egg penetration test. Hum Reprod 1998; 13:1928.
  82. Zainul Rashid MR, Fishel SB, Thornton S, et al. The predictive value of the zona-free hamster egg penetration test in relation to in-vitro fertilization at various insemination concentrations. Hum Reprod 1998; 13:624.
  83. Gump DW, Gibson M, Ashikaga T. Lack of association between genital mycoplasmas and infertility. N Engl J Med 1984; 310:937.
  84. Kallen CB, Arici A. Immune testing in fertility practice: truth or deception? Curr Opin Obstet Gynecol 2003; 15:225.
  85. Papanikolaou EG, Vernaeve V, Kolibianakis E, et al. Is chromosome analysis mandatory in the initial investigation of normovulatory women seeking infertility treatment? Hum Reprod 2005; 20:2899.
  86. Riccaboni A, Lalatta F, Caliari I, et al. Genetic screening in 2,710 infertile candidate couples for assisted reproductive techniques: results of application of Italian guidelines for the appropriate use of genetic tests. Fertil Steril 2008; 89:800.