infertility
INFERTILITY
Treatment Guideline Chart

Infertility is the failure to achieve pregnancy after a year of unprotected regular intercourse or therapeutic donor insemination in women <35 years old or within 6 months in women >35 years old.

It can be primary if no pregnancy has ever occurred or secondary if pregnancy has occurred irrespective of the outcome.

Ovulation induction is part of the patient's management for polycystic ovarian syndrome which aims to achieve development of a single follicle and subsequent ovulation in a woman with anovulation.

Infertility References

  1. Society of Obstetricians and Gynaecologists of Canada. Endometriosis: diagnosis and management. Journal of Obstetrics and Gynaecology Canada. 2010;32(7):S1-S32. http://www.sogc.org. Accessed 19 Jul 2011. PMID: 21545757
  2. ACOG Committee on Practice Bulletins - Gynecology. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul;116(1):223-236. doi: 10.1097/AOG.0b013e3181e8b073. PMID: 20567196
  3. Bukulmez O, Arici A. Luteal phase defect: myth or reality. Obstet Gynecol Clin North Am. 2004 Dec;31(4):727-744. PMID: 15550332
  4. Ashrafi M, Moni A, Mohammadzadeh A, et al. A comparative study of GnRH antagonists and GnRH agonists in PCO patients undergoing IVF/ICSI cycles. Iranian J Reprod Med. 2005;3(1):14-18. http://www.ijrm.ir.
  5. Braude P, Rowell P. Assisted conception. II--in vitro fertilisation and intracytoplasmic sperm injection. BMJ. 2003 Oct;327(7419):852-855. PMID: 14551103
  6. Braude P, Rowell P. Assisted conception. III--problems with assisted conception. BMJ. 2003 Oct;327(7420):920-923. PMID: 14563758
  7. Collins J. Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Current best evidence for the advanced treatment of unexplained subfertility. Hum Reprod. 2003 May;18(5):907-912. PMID: 12721160
  8. Cahill DJ, Wardle P. Management of infertility. BMJ. 2002 Jul;325(7354):28-32. PMID: 12098728
  9. Devroey P, Fauser BC, Diedrich K; Evian Annual Reproduction (EVAR) Workshop Group 2008. Approaches to improve the diagnosis and management of infertility. Hum Reprod Update. 2009;15(4):391-408. http://www.ncbi.nlm.nih.gov/pubmed. PMID: 19380415
  10. Gharib S, Chapin MD, Rein MS, et al. Infertility: a guide to evaluation, treatment, and counseling. Boston (MA): Brigham and Women's Hospital. 2003
  11. Hamilton-Fairly DH, Taylor A. ABC of subfertility. Anovulation. BMJ. 2003;327(7414):546-549. http://www.ncbi.nlm.nih.gov. PMID: 12958117
  12. Forti G, Krausz C. Clinical review 100: Evaluation and treatment of the infertile couple. J Clin Endocrinol Metab. 1998 Dec;83(12):4177-4188. PMID: 9851748
  13. Hart R. Unexplained infertility, endometriosis, and fibroids. BMJ. 2003 Sep;327(7417):721-724. PMID: 14512481
  14. Homburg R. The management of infertility associated with polycystic ovary syndrome. Reprod Biol Endocrinol. 2003 Nov;1:109. PMID: 14617367
  15. Jones HW Jr, Toner JP. The infertile couple. N Engl J Med. 1993 Dec;329(23):1710-1715. PMID: 8166801
  16. Hughes E, Brown J, Collins JJ, et al. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev. 2010 Jan(1). https://researchspace.auckland.ac.nz/bitstream/handle/2292/9628/14651858.CD000057.pub2.pdf?sequence=4. Accessed 12 Feb 2013. PMID: 20091498
  17. Kalro BN. Impaired fertility caused by endocrine dysfunction in women. Endocrinol Metab Clin North Am. 2003 Sep;32(3):573-592. PMID: 14575026
  18. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-288. http://jcem.endojournals.org/content/96/2/273.full.pdf+html. Accessed 12 Feb 2013. PMID: 21296991
  19. Jose-Miller AB, Boyden JW, Frey KA. Infertility. Am Fam Physician. 2007 Mar;75(6):849-856. PMID: 17390595
  20. Practice Committee of the American Society for Reproductive Medicine; The Practice Committee of the Society for Assisted Reproductive Technology. 2008 guidelines for gamete and embryo donation: a practice committee report. Fertil Steril. 2008 Nov;90(2):S30-S44. http://www.ncbi.nlm.nih.gov/pubmed. PMID: 19007645
  21. Practice Committee of the American Society for Reproductive Medicine. The clinical relevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2012 Nov;98(5):1112-1117. http://www.asrm.org. Accessed 12 Feb 2013. PMID: 22819186
  22. Rowell P, Braude P. Assisted conception. I-General principles. BMJ. 2003 Oct;327(7418):799-801. PMID: 14525882
  23. Smith S, Pfeifer S, Collins J. Diagnosis and management of female infertility. JAMA. 2003 Oct;290(13):1767-1770. PMID: 14519712
  24. Seyhan A, Ata B. The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonists. Int J Womens Health. 2011 Mar;3:243-255. doi: 10.2147/IJWH.S15002. PMID: 21892335
  25. Youssef MAFM, Al-Inany HG, Aboulghar M, et al. Recombinant versus urinary human chorionic gonadothrophin for final oocyte maturation trigerring in IVF and ICSI cycles. Cochrane Database Syst Rev. 2011 Apr;4. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003719.pub3/pdf/abstract. Accessed 12 Feb 2013. PMID: 21491386
  26. Ludwig M, Howles CM. Optimisation of ovarian stimulation protocols for assisted reproduction. 1st ed: CMP Medica; 2005 Jun
  27. MedWormhttp://www.medworm.com/rss/index.php/Endocrinology/15/http://www.medworm.com/rss/medicalfeeds/specialities/Endocrinology.xml
  28. MedWormhttp://www.medworm.com/rss/index.php/OBGYN/29/http://www.medworm.com/rss/medicalfeeds/specialities/OBGYN.xml
  29. Shenenberger D. Hyperprolactinemia. eMedicine. http://emedicine.medscape.com. Oct 2005.
  30. Petrozza JC. Assisted reproduction technology. eMedicine. http://www.emedicine.com. Jul 2006.
  31. American Society for Reproductive Medicine. Assisted reproductive technologies: a guide for patients. American Society for Reproductive Medicine. http://www.asrm.org. 2008.
  32. Wellbery C. Diagnosis and treatment of endometriosis. AAFP. http://www.aafp.org. Oct 1999.
  33. Vayena E, Rowe PJ, Griffin PD, eds. Current practices and controversies in assisted reproduction: report of a WHO meeting on medical, ethical, and social aspects of assisted reproduction; Sep 17-21, 2001; Geneva, (Switzerland). Section 3, Ovarian stimulation for assisted reproductive technologies. WHO. http://whqlibdoc.who.int. Sep 2001.
  34. National Institute for Health and Care Excellence. Fertility: assessment and treatment for people with fertility problem: NICE Clinical Guideline 156. NICE. http://www.nice.org.uk. Feb 2013. Accessed 25 Jun 2013.
  35. National Collaborating Centre for Women's and Children's Health. Fertility: assessment and treatment for people with fertility problems. NICE. http://www.nice.org.uk. Feb 2004.
  36. Hong Kong College of Obstetricians and Gynaecologists. Guideline on induction of ovulation. HKCOG guidelines number 14. http://hkcog.obg.cuhk.edu.hk. Mar 2011. Accessed 12 Feb 2013.
  37. Garcia JE. Infertility. eMedicine. http://www.emedicine.com. 2006.
  38. Royal College of Obstetricians and Gynaecologists. Infertility: RCOG guidelines. RCOG. http://www.rcog.org.uk. Jun 2010.
  39. American College of Obstetricians and Gynecologists (ACOG). Management of recurrent early pregnancy loss [summary in National Guideline Clearinghouse]. http://www.guideline.gov. Feb 2001
  40. Evidence-based guideline for the assessment and management of polycystic ovary syndrome. Jean Hailes Foundation for Women’s Health on behalf of the PCOS Australian Alliance; Melbourne, 2011. http://www.adelaide.edu.au. 2011. Accessed 12 Feb 2013.
  41. Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. Ovulation induction in polycystic ovary syndrome. SOGC clinical practice guideline no. 242. SOGC. http://sogc.org. May 2010. Accessed 11 Feb 2013.
  42. American Society for Reproductive Medicine. Medications for inducing ovulation: a guide for patients. American Society for Reproductive Medicine. http://www.asrm.org. 2006
  43. Ginsburg ES. Procedure for intrauterine insemination. UpToDate. http://www.uptodate.com. Jan 2013
  44. The Royal College of Obstetricians and Gynaecologists. The investigation and management of endometriosis. Guideline no. 24. RCOG. http://www.rcog.org.uk. Oct 2006.
  45. Loh SF, Agarwal R, Chan J, et al. Academy of Medicine-Ministry of Health clinical practice guidelines: assessment and management of infertility at primary healthcare level. Singapore Med J. 2014 Feb;55(2):58-65. http://www.sma.org.sg. PMID: 24570313
  46. Okun N, Sierra S, Society of Obstetricians and Gynaecologists of Canada. Pregnancy outcomes after assisted human reproduction. J Obstet Gynaecol Can. 2014 Jan;36(1):64-83. http://sogc.org. Accessed 19 May 2014. PMID: 24444289
  47. Kersten FA, Hermens RP, Braat DD, et al. Overtreatment in couples with unexplained infertility. Hum Reprod. 2015 Jan;30(1):71-80. doi: 10.1093/humrep/deu262. Accessed 28 Apr 2015. PMID: 25336712
  48. Kuohung W, Hornstein MD. Overview of treatment of female infertility. UpToDate. http://www.uptodate.com. 17 Apr 2015. Accessed 27 Apr 2015.
  49. Legro RS, Brzyski RG, Diamond MP, et al; NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014 Jul 10;371(2):119-129. doi: 10.1056/NEJMoa1313517. PMID: 25006718
  50. Subramaniam R, Sinthamoney E, Damodaran P, et al. Clinical guidelines for the management of endometriosis 2016. Obstetrical and Gynaecological Society of Malaysia (OGSM). http://www.ogsm.org.my. 2016. Accessed 24 Jan 2017.
  51. National Institute for Health and Care Excellence. Fertility problems: assessment and treatment. NICE. https://www.nice.org.uk. Updated Aug 2016. Accessed 02 Mar 2017.
  52. World Health Organization (WHO). Global prevalence of infertility, infecundity and childlessness. WHO. http://www.who.int. 2017. Accessed 02 Mar 2017.
  53. Wang R, Kim BV, van Wely M, et al. Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. BMJ. 2017 Jan 31;356:j138. doi: 10.1136/bmj.j138. Accessed 02 May 2017. PMID: 28143834
  54. European Medicines Agency. Elonva summary of product characteristics. EMA website. http://www.ema.europa.eu. 11 Dec 2015. Accessed 02 May 2017.
  55. Liu W, Dong S, Li Y, et al. Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome. Exp Ther Med. 2015 Oct;10(4):1297-1302. doi: 10.3892/etm.2015.2690. Accessed 02 May 2017. PMID: 26622481
  56. Fauser BCJM. Overview of ovulation induction. UpToDate. https://www.uptodate.com. 30 Nov 2021. Accessed 11 May 2017.
  57. Snyder PJ. Causes of hyperprolactinemia. UpToDate. https://www.uptodate.com. Mar 2017. Accessed 6 Sep 2017.
  58. Snyder PJ. Patient education: high prolactin levels and prolactinomas. UpToDate. https://www.uptodate.com. Jul 2017. Accessed 6 Sep 2017.
  59. Practice Committee of the American Society for Reproductive Medicine. Comparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline. Fertil Steril. 2018 Jun;109(6):993-999. doi: 10.1016/j.fertnstert.2018.03.019. PMID: 29935660
  60. Teede HJ, Misso ML, Costello MF, et al; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2018 Jul 19. doi: 10.1111/cen.13795. PMID: 30024653
  61. Centre for Research Excellence in Polycystic Ovary Syndrome (CREPCOS), European Society of Human Reproduction and Embryology (ESHRE) and American Society of Reproductive Medicine (ASRM). International evidence-based guideline for the assessment and management of polycystic ovary syndrome (PCOS). ESHRE. https://www.eshre.eu. 2018.
  62. Kuohung W, Hornstein MD. Treatments for female infertility. UpToDate. https://www.uptodate.com. 22 Jul 2021. Accessed 21 Feb 2022.
  63. Practice Committee of the American Society for Reproductive Medicine. The role of immunotherapy in in vitro fertilization: a guideline. Fertil Steril. 2018 Aug;110(3):387-400. doi: 10.1016/j.fertnstert.2018.05.009. PMID: 30098685
  64. American College of Obstetricians and Gynecologists’ Committee of Gynecologic Practice, American Society for Reproductive Medicine. Infertility workup for the women’s health specialist: ACOG Committee opinion, number 781. Obstet Gynecol. 2019 Jun;133(6):e377-e384. doi: 0.1097/AOG.0000000000003271. PMID: 31135764
  65. Buckett W, Sierra S. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019 Oct;39(4):633-640. doi: 10.1016/j.rbmo.2019.05.023. PMID: 31439397
  66. Costello MF, Misso ML, Balen A, et al. Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility. Hum Reprod Open. 2019 Jan;2019(1):hoy021. doi: 10.1093/hropen/hoy021. PMID: 31486807
  67. Hornstein MD, Gibbons WE. Unexplained infertility. UpToDate. https://www.uptodate.com. 12 Apr 2020.
  68. Hunt S, Vollenhoven B. Assessment of female fertility in the general practice setting. Aust J Gen Pract. 2020 Jun;49(6):304-308. doi: 10.31128/AJGP-01-20-5205. PMID: 32464730
  69. Myers ER, Eeaton JL, McElligot KA, et al. Management of infertility. Comparative effectiveness review no. 217. Rockville, MD: Agency for Healthcare Research and Quality. May 2019. doi: https://www.effectivehealthcare.ahrq.gov.
  70. Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020 Feb;113(2):305-322. doi: 10.1016/j.fertnstert.2019.10.014. PMID: 32106976
  71. Practice Committee of the American Society for Reproductive Medicine. Role of tubal surgery in the era of assisted reproductive technology: a committee opinion. Fertil Steril. 2021 May;115(5):1143-1150. doi: 10.1016/j.fertnstert.2021.01.051.
  72. The ESHRE Guideline Group on Reproductive Endocrinology; Bosch E, Broer S, Griesinger G, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2020 May;2020(2):hoaa009. doi: 10.1093/hropen/hoaa009. PMID: 32395637
  73. Toth B, Baston-Büst DM, Behre HM, et al. Diagnosis and therapy before assisted reproductive treatments. Guideline of the DGGG, OEGGG and SGGG (S2K level, AWMF register number 015-085, February 2019) – part I, basic assessment of the woman. Geburtshilfe Frauenheilkd. 2019 Dec;79(12):1278-1292. doi: 10.1055/a-1017-3389. Accessed 10 May 2021. PMID: 31875858
  74. Kunev AK. Diagnostics and treatment of cervical causes of infertility. J Biomed Clin Res. 2019 Dec;12(1):33-39. doi: 10.2478/jbcr-2019-0005.
  75. Balen AH, Morley LC, Misso M, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016 Nov;22(6):687-708. doi: 10.1093/humupd/dmw025. Accessed 21 Feb 2022. PMID: 27511809
  76. Centre for Research Excellence in Polycystic Ovary Syndrome (CREPCOS), Monash University, American Society of Reproductive Medicine (ASRM), and European Society of Human Reproduction and Embryology (ESHRE). International evidence-based guideline for the assessment and management of polycystic ovarian syndrome. Monash University. https://www.monash.edu/. Feb 2018.
  77. Drakopoulos P, Bardhi E, Boudry L, et al. Update on the management of poor ovarian response in IVF: the shift from Bolonga criteria to the Poseidon concept. Ther Adv Reprod Health. 2020 Jul;14:2633494120941480. doi: 10.1177/2633494120941480. PMID: 32844159
  78. Ferraretti AP, Marca AL, Fauser BJCM, et al. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-1624. doi: 10.1093/humrep/der092. Accessed 24 Feb 2022. PMID: 21505041
  79. Haakman O, Liang T, Murray K, et al. In vitro fertilization cycles stimulated with follitropin delta result in similar embryo development and quality when compared with cycles stimulated with follitropin alfa or follitropin beta. F S Rep. 2020 Dec;2(1):30-35. doi: 10.1016/j.xfre.2020.12.002. PMID: 34223270
  80. Hornstein MD, Gibbons WE. Endometriosis: treatment of infertility in females. UpToDate. https://www.uptodate.com. 20 Sep 2021.
  81. Jungwirth A, Diemer T, Kopa Z, et al. EAU guidelines on male infertility. EAU. https://uroweb.org/. Mar 2018.
  82. Kakarla N, Bradshaw KD. Evaluation and management of the infertile couple. Glob Libr Women’s Med. 2008. doi: 10.3843/ GLOWM.10321.
  83. Koechling W, Plasin D, Croston GE, et al. Comparative pharmacology of a new recombinant FSH expressed by a human cell line. Endocr Connect. 2017 Jul;6(5):297-305. doi: 10.1530/ EC-17-0067. PMID: 28450423
  84. Kuohung W, Hornstein MD. Causes of female infertility. UpToDate. https://www.uptodate.com. 22 Jul 2022.
  85. Kuohung W, Hornstein MD. Evaluation of female infertility. UpToDate. https://www.uptodate.com. 08 Mar 2021.
  86. Lindsay TJ, Vitrikas KR. Evaluation and treatment of infertility. Am Fam Physician. 2015 Mar;91(5):308-314. Accessed 10 May 2021. PMID: 25822387
  87. Morris ME. Evaluation and management of infertility in females of advancing age. UpToDate. https://www.uptodate.com. 18 Feb 2022.
  88. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012 Sep;98(3):591-598. doi: 10.1016/j. fertnstert.2012.05.031. PMID: 22704630
  89. Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021 Nov;116(5):1255-1265. doi: 10.1016/j.fertnstert.2021.08.038. PMID: 34607703
  90. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measure of ovarian reserve: a committee opinion. Fertil Steril. 2015 Mar;103(3):e9-e17. doi: 10.1016/j.fertnstert.2014.12.093.
  91. Practice Committee of the American Society for Reproductive Medicine. Use of exogenous gonadotropins for ovulation induction in anovulatory women: a committee opinion. Fertil Steril. 2020 Jan;113(1):66-70. doi: 10.1016/j. fertnstert.2019.09.020. PMID: 32033726
  92. Rasool S, Shah D. Fertility with early reduction of ovarian reserve: the last straw that breaks the camel’s back. Fertil Res Pract. 2017 Oct;3:15. doi: 10.1186/s40738-017-0041-1. PMID: 29046817
  93. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. J Urol. 2021 Jan;205(1):36-43. doi: 10.1097/JU.0000000000001521. Accessed 21 Feb 2022. PMID: 33295257
  94. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. J Urol. 2021 Jan;205(1):44-51. doi: 10.1097/JU.0000000000001520. PMID: 33295258
Editor's Recommendations
Special Reports