Ovarian Reserve Testing and Follicular Monotoring |Jindal IVF

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Ovarian reserve assessment and follicular
monitoring
8th ART UPDATE

• Dr. Umesh N. Jindal
• Jindal IVF and Sant Memorial Nursing Home
• 3050, Sector 20 D, Chandigarh

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Response variation and challenges

• Predication of pregnancy
• Prediction of non pregnancy
• Stimulation regimen

V. Poor
Poor

• Unexpected Hypo
• or hyper Response

• Minimize dose

Good
V. Good

• Regimen
• Prediction of OHSS

Hyper
Explosive
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Question 1

• What do you understand by ovarian reserve?
• 1. Reserve capacity of ovaries to regenerate.
• 2. The pool of primordial follicles at the time
  of menarche.
• 3. The number of antral follicles on day 2 of
  menstrual cycle.
• 4. The remaining number of fertilizable follicles
  in ovaries.

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Ovarian Reserve Tests

• Tests
• Clinical
• Age, BMI, Infertility diagnosis
• Sonological
• AFC, ovarian volume and stromal flow indices,
  Flow
• Biochemical, static
• Basal FSH, AMH, Inhibin -B, Basel E2
• Biochemical, dynamic
• Response to various follicle stimulating agents

• End Points
• IVF Outcome
• Prediction of pregnancy
• Prediction of non pregnancy
• Adverse events
• Prediction of cycle cancellation
• Prediction of hyper-response
• Prediction of OHSS
• Prediction of unexpected response
• Optimization
• Selection of stimulation regimen and dose

Clinical utility of any ovarian reserve tests is
assessed by its contribution in decisions making
over and above clinical parameters Relationship
of quality and quantity?
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Clinical assessment of ovarian reserve
All IVF indicated cases
Clinical
Age, BMI, Infertility Diagnosis
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Age and infertility
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Effect on BMI on Ovarian Reserve and IVF outcome
BMI lt23 n () 2327 n ( ) gt27 n () Totaln ()
ß-HCG Negative 25 (47.2) 29 (59.2) 12 (66.7) 66 (55.0)
ß-HCG Positive 28 (52.8) 20 (40.8) 6 (33.3) 54 (45.0)
Total 53 (100.0) 49 (100) 18 (100.0) 120 (100.0)
chi square p.266
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Effect of infertility diagnosis and response and
IVF outcome
Diagnosis OR test Response Outcome
PCOD High AFC High AMH Small Window of safety Risk of OHSS
Endometriosis AFC unreliable Depending upon reserve Average
Tubal factor TB Not tested Poor Less than average
Male factor As expected As expected Good
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Clinical assessment of ovarian reserve
All IVF indicated cases
Clinical
Age, BMI, Infertility Diagnosis
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Question 2

• Which ovarian reserve test would you like to do
  next?
• Day 2-3 FSH
• AMH
• serum inhibin
• ovarian blood flow and volume
• AFC

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Clinical assessment of ovarian reserve
All IVF indicated cases
Clinical
Age, BMI, Infertility Diagnosis
All IVF indicated cases
Ultrasound
AFC
lt4 Poor
gt14 Hyper
5-13 Normal
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Technique Estimating AFC

• Technique
• Day 2-4
• AF 2-10 mm dia
• All planes
• Indentify ovary
• Count all follicleslt 10m
• Add both ov. count

• Requirements
• Training
• Real time 2 D
• T VS, 7 MHZ

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AFC as test of ovarian Reserve
Pitfalls
Advantage

• Ovarian structure
• Position
• Associated pathology
• Expertise, observer dependent
• High resolution ultrasound

• Very strong correlation
• Easy
• Quick
• Reproducible
• Any time of cycle

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Distinguishing low and high responders
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• Main findings

• Other studies

• AFC 2-6 mm
• Most closely related to AMH
• Best predictor of ovarian response
• Related to retrieval of mature oocytes
• AF 6-10 mm quite likely to be atritic
• Among good vs poor responders
• AF (2-6mm) (10.0 6.1 vs 4.5 2.1 001)
• AF (6-10mm) (3.6 2.3 vs 2.6 1.6.1 P.11)
• Constitute 70 of total AFC
• Haedsma et al Hum Reprod 2009

• Decrease in AFC lt6m with ageAFC 2-4 mm
  independent predictor of clinical pregnancy
• Deb et al Hum Reprod 2009
• Although it is quite well identified that reserve
  is actually represented by lt 6m follicle . All
  follicles counted for practicality

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Automated Counting
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Practical Application

• Practical Utility of clinical judgment and pre
  test factors is more important .
• Performing an additional test should give
  additional information.
• Identification of response and outcome is very
  important.
• None of the tests at present very good.
• The tests are used more for counseling than
  decision making.

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Objectives of follicular monitoring
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Question 3

• What do you understand by down regulation ?
• 1.HPO axis has been knocked out by Gn-RH agonists
• 2.Complete endometrial shedding
• 3.No follicular or ovarian activity
• 4.All of the above

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Poor responder

• Considerations before starting IVF
• IVF Outcome
• Prediction of pregnancy ?
• Prediction of non pregnancy ?
• Adverse events
• Prediction of cycle cancellation ?
• Prediction of hyper-response
• Prediction of OHSS
• Prediction of unexpected response ?
• Optimization
• Selection of stimulation regimen and dose ?

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Poor Responder Baseline scan

• Older women
• High range FSH(8-12)
• Low AMH (.3-.6)
• AFC lt4
• Size AFC gt6mm
• Any protocol result remain poor

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Reduced Responder baseline scan

• AFC 4-6
• Young women after ovarian surgery, TB, impending
  POF
• Older women within 8-10 years of menopause
• Fair success
• Age important determinant
• Counseling for cancellation and reduced success
  rate

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Poor responder day 5 scan

• One or two follicles
• Discordant growth
• Poor perifollicular flow
• Unhealthy look
• Will end in empty follicle immature oocytes or
  fertilization failure
• Cancellation and IVF with OD a better option

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Reduced Response d 5,hCG

• Reduced number of follicles
• Discordant follicles
• Low implantation
• Protocol individualized
• IVF not to be delayed

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Adequate Responder baseline scan

• Ideal case
• Have 4-8 AFC
• Do good with any protocol
• Develop 8-12 follicles
• Unexpected poor response with low starting dose
• Both protocols work well
• baseline scan good responder decide starting
  dose.avi

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Plentiful Responder baseline scan

• AFC 8-10 in each ovary
• Develop 10-16 follicles
• Good quality oocytes .
• Good success rate
• Risk of OHSS if starting dose high

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Adequate Response 5,hCG

• Have excellent quality oocytes
• Good success rate
• No risk of OHSS

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Plentiful response d 5,hCG

• Good case for ovum sharing
• Margin of safety less
• Trigger with Gn-RH-a may be a safer option
• If over-stimulated or in planned OD cases

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Hyper Responder

• Considerations before starting IVF
• IVF Outcome
• Prediction of pregnancy
• Prediction of non pregnancy
• Adverse events
• Prediction of cycle cancellation because of poor
  response ?
• Prediction of hyper-response ?
• Prediction of OHSS ?
• Prediction of unexpected response ?
• Optimization
• Selection of stimulation regimen and dose ?

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Hyper responder baseline scan

• PCOD case
• AFC gt12 in each ovary
• Low starting dose
• Cancellation risk high

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Explosive responder baseline scan

• Subgroup of PCOD
• AFCgt25 in each ovary
• Thick stroma
• Young lean as well as obese PCOD
• V high risk of OHSS and cancellation
• Need experience and judgment in stimulation of
  these women

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Hyper Response d 5,hCG

• Antagonist protocol better
• Gn-RH-a trigger can almost eliminate the risk of
  OHSS

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Explosive d 5,hCG
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Newer Tools

• color Doppler vascularity is important but
  direct use is still limited
• 3-D
• Sonovac
• Good predictor of mature follicles
• Does not add to the success rate over 2-D

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Conclusion

• Sonoendocrinology and understanding
  of follicular dynamics as well as functional
  morphology in natural , stimulated and
  manipulated cycles is the key to a successful and
  safe IVF programme.