Female Infertility Evaluation

Author: Dr. Om J Lakhani

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Assessment of ovulatory function

• Q. What point in history generally rules out ovulatory dysfunction?

  • Most likely to be ovulatory:
    • Regular menses every 28 days
    • with molimina symptoms before menses

• Q. If the woman does not give the above history of normal ovulatory cycles, then what is done?

  • Do a mid-lueteal phase progesterone
  • It is done seven days before the expected date of menses (21st day of cycle)
  • If the level is >3 pg/ml- it suggests that ovulation has occurred

• Q. What are other tests for detection of ovulation?

  • Use of Home LH detection kit
  • Ultrasound assessment for ovulation
  • Endometrial biopsy

• Q. What is done if mid-lueteal progesterone is <3 pg/ml?

  • Assessment of ovulatory dysfunction is done
  • Baseline tests include PCOS work up – Ultrasound, testosterone, thyroid function, prolactin, 17 OHP

Assessment of ovarian reserve

• Q. Which patients should undergo ovarian reserve testing?

  • Age >35 years and not conceived for six months
  • Women with risk for POI- radiation exposure, chemotherapy, genetic abnormalities, autoimmune disease, etc

• Q. What is the difference between older women vs. younger women with poor ovarian reserve?

  • Younger women with poor ovarian reserve- have less quantity of ovaries but good quality
  • Older women- vice versa

• Q. What are tests done for assessment of ovarian reserve?

  • Day 3 FSH and estradiol
  • Antral follicular count on TVS
  • Clomiphene challenge test
  • AMH levels

FSH, estradiol, and clomiphene challenge

• Q. When we say day 3, what is day 1?

  • Day 1 is the first day of menstrual flow

• Q. What value of Day 3 FSH suggests normal ovarian reserve, and what suggests abnormal?

  • FSH <10 mIU/ml- normal
  • 10-20- borderline
  • more than 20 mIU/ml- poor ovarian reserve

• Q. What is the fundamental of day 3 FSH?

  • With good ovarian reserve, good amount of hormone production from small antral follicles → suppresses FSH

• Q. What does day three estradiol level suggest ovarian reserve?

  • Day 3 estradiol <80 pg/ml- good ovarian reserve
  • More than 80 pg/ml- poor reserve
  • Very important
    • ASRM says that estradiol interpretation is important mainly in women with normal FSH yet risk of poor ovarian reserve
  • When used alone, it is not very useful

• Q. What is the fundamental measurement of estradiol?

  • High estradiol means premature recruitment of ovarian follicle which occurs in women with poor ovarian reserve
  • Interestingly, this would suppress the FSH, and hence both FSH and estradiol measurements are required

• Q. Describe the clomiphene challenge test?

  • FSH and estradiol are measured on day 3 of the cycle
  • Clomiphene given for days 5 to 9 in a dose of 100 mg
  • FSH again measured on day 10

• Q. What is the interpretation of the clomiphene challenge test?

  • Again, day three and day 10 FSH <10 – normal
  • 10- 20 (some use 15) – inadequate
  • More than 20- poor
  • Estradiol – similar interpretation as earlier

• Q. What is the prognosis of women with poor ovarian reserve?

  • Generally poor prognosis
  • They can rarely conceive without the use of donor oocytes

Antral follicle count

• Q. What is the definition of antral follicles?

  • Measuring 2-10 mm in diameter

• Q. When is a measurement of antral follicle count done?

  • Generally, on days 2-4
  • However, studies have shown that it can be done at any phase of the cycle

• Q. How is AFC count done?

  • It is done by TVS
  • Ovary is assessed in both transverse and longitudinal planes
  • Diameter measured in 2 perpendicular planes and larger of the two dimensions is used for assessment

• Q. What AFC values suggest poor ovarian reserve?

  • Value <4-10 antral follicles on days 2-4 suggest poor ovarian reserve

AMH

• Q. Which follicles secrete AMH?

  • Preanteral follicle- <8 mm
  • Early antral follicles

• Q. What does AMH tell us?

  • AMH tells us the size of the primordial follicular pool
  • Hence it is a good biochemical marker of ovarian reserve

#Pearl

• AMH cutoffs vary according to labs; hence difficult to generalize

• Q. What is the interpretation of AMH?

  • <0.5 ng/ml- very poor ovarian reserve
  • <1 ng/ml - poor
  • 1.0 – 3.5 ng/ml – good ovarian reserve
  • More than 3.5 ng/ml- chance of ovarian hyperstimulation on ovulation induction
  • Newer assay uses cut point of 0.2-0.7 ng/ml

• Q. Does AMH need to be measured in the follicular phase?

  • No
  • It can be measured in any phase of the cycle since the growth of preantral follicles is continuous and not dependent on the phase of the cycle

• Q. Apart from AMH, which other similar test is used to judge ovarian reserve?

  • Inhibin B
  • Cutoff value is 40-45 pg/ml
  • However, it has poor sensitivity and specificity and is hence not used routinely

#Pearl

• The cut points of AMH depends on the assay used
• There is an older assay for AMH and a newer assay that have different cut points
• So, it is important to known which assay is used and what is its cut point for interpretation

Assessment of fallopian tube patency and uterine anatomy

• Q. Which is the first-line assessment of tubal patency?

  • HSG- hysterosalpingography

• Q. What is HyCoSy?

  • Hysteria-salphingo contrast sonography

• Q. What does HSG not tell you?

  • Does not tell you about adhesions and endometriosis
  • It also tells you more about distal tubal blocks – but does not tell you much about the proximal tubal blocks

• Q. What is the gold standard for tubal patency?

  • Laparoscopy with chromotubation

• Q. Which is another suitable non-invasive method for the tubal assessment?

  • Chlamydia trachomatis IgG antibody testing

• Q. What can be a cost-effective approach for tubal disorder?

  • First do chlamydia trachomatis IgG antibody
  • If negative- less likelihood of tubal disease
  • If positive- it can be falsely positive due to cross-reaction with C. pneumonia - hence to HSG
  • If the high risk of tubal disease- do HSG directly

• Q. Which is the test of choice for uterine cavity assessment?

  • Saline infusion sonohysterography
  • It is a special sonography
  • HSG can also assess the uterine abnormality
  • It is confirmed with further imaging like MRI or hysteroscopy

• Q. What is the role of hysteroscopy?

  • It is helpful for diagnosis and treatment of uterine abnormalities

• Q. What can hysteroscopy not tell you?

  • Status of the myometrium
  • Fallopian tube
  • Adnexal structures

#Pearl

• Fallopian and uterine assessment - HSG is a good test

• Uterine assessment alone (patient undergoing IVF)- saline infusion sonohysterography or Hysteroscopy

• Q. What is the role of laparoscopy?

  • It is done for the treatment of endometriosis and fallopian tube blocks
  • If it is done for any other reason- it must be combined with chromotubation to look for tubal patency

Tests with limited clinical utility

• Q. What is the role of endometrial biopsy?

  • To document secretory endometrium- which is a marker of ovulation has occurred
  • To correlate the endometrial timing with that of the IVF date – to assess Luteal phase defect
  • However, this test is rarely done for either indication these days

• Q. What is the fundamental of basal body temperature measurement?

  • Progesterone in the luteal phase affects the hypothalamus and increases basal body temperature

• Q. Describe the process of basal body temperature measurement?

  • Women measures the temperature by keeping the thermometer beneath the tongue every day before getting out of the bed
  • During the luteal phase, the temperature increase by 0.5 F compared to the follicular phase
  • It begins to rise 1-2 days after LH surge and remains high for ten days