Level of AMH correlated with number of antral follicles of ovary. Therefore AMH is taken by indicator of ovarian reserve.

1. Dr.Rokeya Begum
FCPS,MS
1. Graduated from Chittagong Medical College.
2.Working as Professor and advisor of Department of Obs & Gynae, USTC, Chittagong.
3. IVF specialist & Endoscopic Surgeon, Surgiscope Fertility & Endoscopic centre, Chittagong .
4. Special interest in High risk Obstetrics, Infertility & Endoscope.
5. Author of two books:
- Clinical guide to Obstetrics and Gynaecology
- Problem Based Questions Answer and OSCEs in Obstetrics and Gynaecology
6. Receive Life time achievement award in 2016 for Obstetrics and Gynaecology Society of Bangladesh.

3. GREETINGS FROM PORT CITY
CHATTOGRAM

4. SURGISCOPE FERTILITY CENTER

6. Stimulation protocol in
ART: should we tailor it
on AMH level?

7. The success of IVF treatment depends on
obtaining an adequate or sufficient number of
eggs to obtain high quality of transferable
embryos.

8. Pre IVF evaluation
IVF four decade old process still has
success 35-40%.

9. IVF evaluation
- General health
- Reproductive health
Reproductive ability of women is strongly correlated with
Chronological age
Ovarian reserve
Ovary
Tube
Uterus

10. Ovarian reserve measured by-
Antral follicle count (AFC)
Antimullerian hormone (AMH)

11. Antimullarian hormone is being considered as a better predictor
of ovarian reserve because
1. Level can be measured at any time not cycle dependable.
2. Level is not dependent on feed back.
3. Laboratory based
Antral follicle count
1. Clinical based
2. Time dependent

12. Antimullarian hormone
 AMH is expressed in pre antral & small
antral follicles.
 A dimeric glycoprotein belonging to TGF- β
superfamily.

13. It has an inhibitory effect on primordial follicle
recruitment as well as on the responsiveness of
growing follicles to FSH in ovary.
AMH
AFC
+ ve
- ve
Fig: Guddi triangle

14. Level of AMH correlated with number of antral
follicles of ovary.
Therefore AMH is taken by indicator of ovarian
reserve.
Normal level is 1-3 ng/ml.

15. Three groups
1. Hypo responder or low
2. Hyper responder
3. Normal
GROUPS AFC AMH
Low responder <10/ovary <0.5 – 1.0 ng/ml
Normal responder 10-12 1 – 3 ng/ml
Hyper responder >12/ovary > 3.4 ng/ml

16. Ovarian reserve indicates the
fertility potential of a woman at a
particular age by defining the
quantity and quality of primordial
follicular pool.

17. Different steps of IVF
Patient selection
Stimulation
Trigger
OPU
ET

18. Among them stimulation of ovary is the
most important.

20. Stimulation protocol has two objectives:
a)Sufficient number of transferable
embryos at least 10 mature oocyte.
2) Minimize the risk of hyper stimulation.

21. Challenge
1.Excess embryo
Dispose
Cryopreservation
2. Quality of oocyte
3. Cycle cancelation

22. Optimum stimulation protocol should have-
1. Synchronize follicular growth
2. Prevent OHSS
3. Prevent premature LH surge and incidence of premature LH surge is high
with short or ultrashort protocol .
4. Premature elevation of progesterone is associated with lower clinical
pregnancy rate in fresh cycles .
5. Avoid severe pituitary suppression this causes large dose and long duration
of gonadotrophin.
6. Users friendly

23. Stimulation of ovary protocol has
change from one size fits all to tailor
made plan according to patient needs.

24. Ovarian stimulation comprise three basic elements.
a) Exogenous gonadotrophin for multi follicular development.
b)Regulation of pituitary function and /or to prevent premature
ovulation.
Co treatment the GnRh analoges.
GnRh agonist
GnRh antagonist
c) Final maturation trigger 36-38 hrs prior to oocyte retrieval.

25. Stimulation protocols are as follows
1. GnRh agonist
- long agonist
- short agonist
a) Micro-dose Flare protocol
b) Ultrashort Flare protocol.
2. GnRh antagonist
Single dose or multiple dose
a) Flexible
b) Fixed
3. A combination of two protocol (Agonist and Antagonist)
FSH flare up starts from 4-12 hours remain
elevated from 24-34hrs before down
regulation
Antagonist single dose 0.25mg acts within
2-4 hours and last 20-22 hrs.

26. Fig: GnRH long agonist protocol :ET :Embryo transfer; OPU: Ovum pick up.

27. Fig: Micro – dose flare up agonist protocol.

28. Fig: Ultra short agonist protocol

29. Fig: Flexible/Fixed antagonist protocol

30. Fig: Ultra short agonist + flexible antagonist protocol (combination)

31. Agonist protocol versus antagonist
1. Clinical outcome fairly equal between two protocols.
2. Total gonadotrophin dose is reduced.
3. OHSS-less or nil
4. Antagonist now favorable than agonist.

32. Gonadotrophin use for stimulation
 rFSH
 Human menopausal gonadotrophin
 Urinary (u FSH)
 Highly purified (HP-FSH)
Evidence: both equal

33. Addition of LH
 Hypo gonadotrophin hypogonadism
 Poor responder
 Known poor response with previous FSH cycle
 FSH and LH receptor polymorphism

34. Dose of gonadotrophin depends on
• Clinical experience and judgement
• Age
• BMI
• Based FSH
• AFC
• AMH

35. Duration of stimulation
10-12 days.

36. Problem
Poor responder/Poor reserve (DOR)
Hyper responder (PCOD)

37. Diminish ovarian reserve-
Decrease number of viable oocyte may be accompanied by
qualitative decline.
- Advance age
- Young women due to diverse etiological factor
(Genetic Poly morphism)

38. Hyper responder
- Chance of life threatening OHSS.

39. Stimulation protocol for DOR
 Antagonist
 Mild stimulation
 Short or ultrashort protocol
 Agonist and antagonist
 IVF lite / embryo pooling (Repeated cycle)

40. Mini dose
protocol
Micro dose flare up
protocol
Ultra short agonist
protocol
Combination
protocol
Modify
stimulation
protocol
Conventional
Agonist
protocol –
Dampening of
ovarian
response to
gonadotrophin

41. Modify
stimulation
protocol
Antagonist protocol - -
Decrease stimulation
duration
- Fewer cancellations
- Lesser
Gonadotrophins

43. The theory of a multicyclic development of follicles during the
menstrual cycle prompted new approaches to ovarian stimulation
such as starting gonadotrophins for ovarian stimulation at any
time during the menstrual cycle or using double stimulation
during it, with stimulation in both the follicular and luteal
phases.

44. Follicular waves

45. Fig: Double stimulation regimens: two successive ovarian stimulations with two oocyte retrievals at the end
of both ovarian stimulations are performed in less than 1 month. The first ovarian stimulation starts during
the early follicular phase and the second can begin the day after the first oocyte retrieval.

46. Fig: Double randomly started ovarian stimulation (Double Random-OS): two successive ovarian
stimulations with two oocyte retrievals at the end of both ovarian stimulations are performed in
approximately 25 days. The first ovarian stimulation can start randomly during the menstrual cycle (e.g.
during the luteal phase), and the second can begin the day after the first oocyte retrieval. If ovarian
stimulation starts during the luteal phase normally after some days of gonadotrophin therapy menstruation

47. Hyper responder
Modify
stimulation
protocol
 Cryo preservation
 Avoid fresh
transfer/Endogenous
hCG
 Antagonist protocol
 Trigger by GnRh agonist
hCG half life 24 hrs
GnRh agonist – 60 min
Dual trigger

48. Adjuvant therapy
The agents, tools, or procedures that can be implemented
along side the core ART.
Specific adjuvant for specific patient
Rationalize and individualized while treating infertile
patient with adjuvant.

49. Adjuvant therapy
Growth Hormone
Androgens
soft protocol
r-LH
L-arginine, steroids,
aspirin
Modify
stimulation
protocol
Oestradial valerate
PRP
(platelet rich plasma)

50. Adjuvant therapy
1.Essential prohormone in follicular
steroidogenesis.
2.Improves the ovarian micromilieu
3.Micronised DHES – 25mg TID X 4
months
4.Improves pregnancy rates and reduces
miscarriage rates.
Androgens

51. Adjuvant therapy
1. Potentiates effect of FSH
2. Previous poor responders have proven benefit.
3. Costly
4. Not widely available
5. No consensus on dose/route
Growth
Hormone

52. Adjuvant therapy
1. LH plays a role in follicular development
2. From D8, 75- 150 Iu
3. Beneficial in a subset of
a. age >35
b. previous POR
c. Antagonist cycles
4. Improves pregnancy rates
r-LH

53. Adjuvant for hyper responder
1 Life style – weight reduction
2 Insulin sensitizer
3 Antioxidant
4 Vitamin D
5 Aspirin
Adjuvant * Metformin
* Myoinositol and
D-chiroinositol

54. Conclusion
Choosing a right protocol is still a widely debated topic and requires
years of clinical experience .
currently there are no guidelines recommending the use of drugs
which are available today.