The Workup of Fertility Disorders

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The Work-up of Fertility Disorders

• Jon Havelock, MD, FRCSC, DABOG
• Co-Director
• Pacific Centre for Reproductive Medicine
• November 22, 2007 _at_ 1010

jhavelock_at_pacificfertility.ca
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• Presentation may be found at
• www.pacificfertility.ca

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Infertility

• Lack of conception after 1 year of regular,
  unprotected intercourse
• 85 of couples conceive within 1 year
• 93 of couples conceive within 2 years
• lt 35 years of age
• Seek infertility investigation and management
  after 12 months of trying
• 35 years of age
• Seek infertility investigation and management
  after 6 months of trying

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Infertility Work-up
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Regular Coitus

• Conception occurs on day of and 5 days before
  ovulation1
• Only 6 of pregnancies can be attributed to sperm
  3 days old
• Probability of pregnancy is 37 with daily vs 15
  when weekly

1. Wilcox AJ et al. N Engl J Med 1995. 3331517-21
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Ageing and Ovarian Reserve
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Ageing and Ovarian Reserve
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Ovarian Reserve Testing

• Basal Testing

• Dynamic Testing

• Day 3 FSH
• Day 3 Estradiol
• Antral Follicle Count
• Day 3 Inhibin
• Day 3 Antimüllerian Hormone
• Ovarian Volume Measurements

• Clomiphene Citrate Challenge Test (CCCT)
• Exogenous FSH Ovarian Reserve Test (EFORT)
• GnRH agonist stimulation test (GAST)

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Ovarian Reserve Testing

• Day 3 FSH
• Pituitary hormone measured by chemiluminescent
  assay
• Kept low in the early follicular phase by
  feedback inhibition from Inihibin B production
  from the ovary
• Normal range varies
• 10 IU/L often cut-off for abnormal
• Often used for predicting In Vitro Fertilization
• Pregnancy OR 0.58 when 10 IU/L1
• Sensitivity 7 and Positive Predictive Value
  902
• All infertility patients should be screened

• Yanushpolsky EH, et al. Fertil Steril 2003.
  80111-115
• Jain T et al. Fertil Steril 2004. 82 180-185

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Ovarian Reserve Testing

• Day 3 Estradiol
• Ovarian steroid measured by chemiluminescent
  assay
• Production stimulated by FSH
• Minor feedback inhibition role on FSH secretion
  at the anterior pituitary
• Elevated day 3 levels indicate subtle FSH
  increases not detected by assay
• Normal range lt 300 pM
• Often used for predicting In Vitro Fertilization
  outcomes

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Ovarian Reserve Testing

• Clomiphene Citrate Challenge Test
• Stress test of the ovary
• Mechanics of Test
• Day 3 FSH level
• Clomiphene Citrate 100 mg daily from days 5-9 of
  cycle
• Day 10 FSH level
• Often used for predicting In Vitro Fertilization
  outcomes
• Pregnancy OR 0.40-0.58 when 10 IU/L on either
  day 3 or 101
• Sensitivity 26 and Positive Predictive Value
  902
• Age gt 35-40
• Unexplained infertility gt 2 years

• Yanushpolsky EH, et al. Fertil Steril 2003.
  80111-115
• Jain T et al. Fertil Steril 2004. 82 180-185

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Ovarian Reserve Testing

• Antral Follicle Count (AFC)
• Performed in the early follicular phase
• Endovaginal ultrasound
• Determination of follicles between 2-9 mm in each
  ovary
• Normal values
• 4-10 per ovary
• Before age of 37 - AFC mean yearly decline of
  4.81
• After age of 37 - mean yearly decline of11.7

• Scheffer GJ et al. Fertil Steril 1999. 72 845-51

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Polycystic Ovary Syndrome

• Diagnosis of Exclusion
• 2003 Rotterdam Criteria (2 of 3 required)
• Oligo and/or anovulation
• Polycystic ovaries on ultrasound
• Clinical or biochemical evidence of
  hyperandrogenism
• Must exclude other etiologies of anovulation and
  hyperandrogenism

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Polycystic Ovary Syndrome
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Documentation of Ovulation

• Regular menstrual cycles1
• 24-35 days
• Basal Body Temperature
• Rise of 0.4 0C for 11 days
• Endometrial Biopsy
• Midluteal Serum Progesterone
• Test 7 days before expected menses
• 10 nM consistent with ovulation2

• Malcolm CE et al. Obstet Gynecol 2003. 102
  317-318
• Israel R et al. Am J Obstet Gynecol 1972. 1972
  112 1043-1046

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Documentation of Ovulation - LH Kit testing

• Chemiluminescent polyclonal-monoclonal antibody
  assay
• Ovulation occurs 20-24 hours post urine LH surge
• Many commercially available products
• Clear Blue, First Response
• Never shown to increase pregnancy rates

• Miller PB et al. Obstet Gynecol 1996. 87 13-17

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Documentation of Ovulation - Fertility Monitors

• Clear Blue Easy Fertility Monitor
• Measures estrone-3 glucuronide and LH surge
• Metabolite of estradiol
• Rises 1-5 days before the LH surge to identify
  peak fertility
• 91 effective in identifying LH surge

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Male Factor

• Semenanalysis
• Abstinence from 2-5 days
• Masturbated specimen into sterile container and
  examined within 1 hour
• If any abnormality, repeat sample
• Not a test of fertility
• Does not assess sperm function

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Documentation of Adequate Sperm Parameters - WHO

• Liquefaction within 60 minutes
• Appearance homogeneous, grey
• Consistency not viscous
• Volume 2.0 mL

• Concentration 20 million/mL
• Total sperm count 40 million/mL
• Motility 50
• Morphology gt 14
• pH 7.2
• WBC 1 million/mL

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Documentation of Adequate Sperm Parameters
1. Guzick D et al, N Engl J Med 1999.
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Turek PJ et al. Nat Clin Pract Urol 2005.
2226-238
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Utero-Tubal/Peritoneal Factors

• Hysterosalpingogram
• Screening test for uterine and tubal
  abnormalities
• Performed between days 8-14 of menstrual cycle
• May have a therapeutic component in first 1-6
  months post-procedure
• Typically with oil-based contrast
• Uterine abnormalities need further evaluation by
  hysteroscopy
• Tubal abnormalities need further evaluation by
  laparoscopy

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Utero-Tubal/Peritoneal Factors - Hydrosalpinx
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Utero-Tubal/Peritoneal Factors Uterine Septum
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Utero-Tubal/Peritoneal Factors Uterine Filling
Defects