Ovarian Reserve Testing and Follicular Monitoring

1. 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

2. 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

3. 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.

4. 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?

5. Clinical assessment of ovarian reserve All IVF indicated cases Clinical Age, BMI, Infertility Diagnosis

6. Age and infertility

7. Effect on BMI on Ovarian Reserve and IVF outcome chi square p=.266

8. Effect of infertility diagnosis and response and IVF outcome

9. Clinical assessment of ovarian reserve All IVF indicated cases Clinical Age, BMI, Infertility Diagnosis

10. 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

11. Clinical assessment of ovarian reserve All IVF indicated cases Clinical Age, BMI, Infertility Diagnosis All IVF indicated cases Ultrasound AFC <4 Poor >14 Hyper 5-13 Normal

12. Technique Estimating AFC • Technique • Day 2-4 • AF 2-10 mm dia • All planes • Indentify ovary • Count all follicles< 10m • Add both ov. count • Requirements • Training • Real time 2 D • T VS, 7 MHZ

13. 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

14. Distinguishing low and high responders

15. Main findings Other studies Decrease in AFC <6m 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 < 6m follicle . All follicles counted for practicality • 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

16. Automated Counting

17. 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.

18. Objectives of follicular monitoring

19. 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

20. 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 

21. Poor Responder Baseline scan Older women High range FSH(8-12) Low AMH (.3-.6) AFC <4 Size AFC >6mm Any protocol result remain poor

22. 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

23. 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

24. Reduced Response d 5,hCG • Reduced number of follicles • Discordant follicles • Low implantation • Protocol individualized • IVF not to be delayed

25. 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

26. 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

27. Adequate Response 5,hCG • Have excellent quality oocytes • Good success rate • No risk of OHSS

28. 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

29. 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 

30. Hyper responder baseline scan • PCOD case • AFC >12 in each ovary • Low starting dose • Cancellation risk high

31. Explosive responder baseline scan • Subgroup of PCOD • AFC>25 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

32. Hyper Response d 5,hCG • Antagonist protocol better • Gn-RH-a trigger can almost eliminate the risk of OHSS

33. Explosive d 5,hCG

34. 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

35. 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.