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female infertility

Inability to conceive within 1 year or regular unprotected sexual intercourse (6 months if > 35 years of age). Etiology: - ovarian failure* - polycystic ovary syndrome is the most common cause of anovulatory infertility [1] - thyroid disease - hyperprolactinemia - viral infection may play a role in unexplained infertility, especially HHV6-A [7] - ciliary dyskinesia - cystic fibrosis * regular menses correlates with regular ovulation Pathology: - antibodies associated with infertility include: - anti-SPAG8 History: - medical history of both partners - menstrual history - history of sexually-transmitted disease - pelvic surgery - history of obstetric complications - miscarriage - C-section Laboratory: - serum TSH - serum prolactin - semen analysis of male partner - serum progesterone (mid-luteal phase) 1 week prior to expected menses - serum FSH on day 3 of the menstrual cycle - < 10 miU/mL, higher levels indicate poor ovarian stimulation & inability to conceive [10] - LH in urine 24-48 hours prior to ovulation - serum antimullerian hormone - see ARUP consult [3] Special laboratory: - pelvic ultrasound - hysterosalpingography 6-10 days into the menstrual cycle to evaluate for uterine or fallopian tube abnormalities - especially with history of pelvic inflammatory disease [1] - endometrial biopsy NOT useful [2] Management: - both partners should be evaluated concurrently as multiple factors may be present [1] - refer to reproductive endocrinologist if - results of initial testing are normal [1] - serum FSH on day 3 of the menstrual cycle is high [10] - serum antimullerian hormone is low [10] - weight reduction in obese women does not improve chances of delivering a healthy baby vaginally [6] - assisted reproduction technology - clomiphene citrate may be useful if testing is negative - gonadotropins (GnRH agonists & GnRH antagonists) also used - letrozole superior to clomiphene for anovulatory infertility [8] - intrauterine insemination with ovarian stimulation superior to expectant management [9] Notes: - gonadotropins associated with more multiple gestations & triplet pregnancies than clomiphene - live birth rate is 23% with clomiphene, & 32% with gonadotropins - letrozole with 19% live birth rate otherwise similar to clomiphene, but is not FDA-approved or recommended [4]

Related

assisted reproduction technology (ART) hypogonadism

Specific

idiopathic oligospermia

General

infertility

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022.
  2. Journal Watch 24(12):95-96, 2004 Murray MJ, Meyer WR, Zaino RJ, Lessey BA, Novotny DB, Ireland K, Zeng D, Fritz MA. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril. 2004 May;81(5):1333-43. PMID: 15136099
  3. ARUP Consult: Infertility The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/infertility
  4. Diamond MP et al Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. N Engl J Med 2015; 373:1230-1240. September 24, 2015 PMID: 26398071 http://www.nejm.org/doi/full/10.1056/NEJMoa1414827
  5. Maheux-Lacroix S, Boutin A, Moore L et al Hysterosalpingosonography for diagnosing tubal occlusion in subfertile women: a systematic review with meta-analysis. Hum Reprod. 2014 May;29(5):953-63. Review. PMID: 24578476 Free Article
  6. Mutsaerts MAQ et al Randomized Trial of a Lifestyle Program in Obese Infertile Women. N Engl J Med 2016; 374:1942-1953May 19, 2016 PMID: 27192672 http://www.nejm.org/doi/full/10.1056/NEJMoa1505297
  7. Marci R, Gentili V, Bortolotti D et al Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLoS One. 2016 Jul 1;11(7):e0158304. eCollection 2016. PMID: 27367597 Free PMC Article
  8. Wang R et al. Treatment strategies for women with WHO group II anovulation: Systematic review and network meta-analysis. BMJ 2017 Jan 31; 356:j138 PMID: 28143834 Free full text http://www.bmj.com/content/356/bmj.j138
  9. Farquhar CM, Liu E, Armstrong S et al Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial. Lancet. Nov 23, 2017 PMID: 29174128 http://thelancet.com/journals/lancet/article/PIIS0140-6736(17)32406-6/fulltext - Nandi A, El-Toukhy T Stimulated intrauterine insemination for unexplained subfertility. Lancet. Nov 23, 2017 PMID: 29174130 http://thelancet.com/journals/lancet/article/PIIS0140-6736(17)33038-6/fulltext
  10. NEJM Knowledge+ - Cox L, Liu JH. Primary ovarian insufficiency: an update. Int J Womens Health. 2014 Feb 20;6:235-43. PMID: 24591848 PMCID: PMC3934663 Free PMC article. Review.