What are factors to be considered Ovarian reserve Previous ovarian response Basic hormone profile Role of FSH & LH Trigger Luteal phase support Pregnancy rate/cycle

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2. Ovulation Stimulation
Dr.Bharati Dhorepatil 2

3. What are factors to be considered
• Ovarian reserve
• Previous ovarian response
• Basic hormone profile
• Role of FSH & LH
• Trigger
• Luteal phase support
• Pregnancy rate/cycle
Dr.Bharati Dhorepatil 3

4. After effects of the stimulation
• Oocyte quality
• Endo quality
• Embryo quality comparision between
conventional Vs minimal stimulation
• Difficulties with this approach
• Can we make it truly costeffective …to make
low cost IVF procedure in our developing
country..INDIA
Dr.Bharati Dhorepatil 4

5. Decision making investigations
• AMH
• USG..Blood flow indices in folliculometry
• PCOS..Hormonal parameters & interpretaion
• Statistical evaluation of success of treatment
• Sperm function tests
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6. Age and Fertility
Optimal
Fertility
Declining
Fertility
Menopause
End of
Fertility
Irregular
Cycles
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7. Ovarian reserve tests provide an indirect measure of the cohort of
recruitable antral follicles present in the FSH window at the
beginning of each menstrual cycle..Functional Ovarian Reserve
Fauser and Van Heusden, 1997; McGee and Hsueh,
2000.
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8. Concept to remember
• Up to 30 years of age, the loss of follicles (and oocytes)
in the human ovary is mainly due to atresia of resting
follicles.
• After reaching a critical threshold in the number of
follicles (estimated at 25,000), the recruitment of growing
follicles is increased twofold and thereafter the loss of
follicles is mainly due to atresia of growing follicles
Gougeon 1996, Erickson 2000.
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9. On the basis of a fixed interval of 13 years
between onset of accelerated decline of fertility
(25,000 remaining follicles) and the menopause,
it can be speculated that women who become
menopausal by the age of 45 years, have experienced
an accelerated decline of fertility around the age of 32.
These women can be classified under a separate
clinical entity, “early ovarian ageing”
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10. Asymptomatic group…
Epidemiological studies have shown that
• 10% of women in the general population
become menopausal by the age of 45
(Treloar, 1981; van Noord et al., 1997),
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11. Clinical suspects…..
• Age 30-35yrs
• Women with a family history of an early menopause
• Unexplained Infertility
• Poor stimulation
• Recurrent cyst formation
• A short follicular phase,
• Early LH surge,
• Premature elevation of progesterone
(P4)
• Requiring very high gonadotrophin doses
• Idiopathic Recurrent abortions with anupleidies
(Farhi et al., 1997; Crosignani et al., 2000; De Boer et al., 2002; Nikolaou et al.,
2002;Lawson et al., 2003)
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12. • Chemotherapy
• Radiotherapy
• Pelvic surgery (Lass et al., 1998;Tulandi et al., 2002),
• Pelvic infections or tubal disease (Keayet al., 1998;
Sharara1998),
• Severe endometriosis (Barnhart et al., 2002),
• Heavy smoking (Augood et al., 1998).
• Single ovary
• Long Standing Hypothyriod status
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13. Antral follicle count (AFC)
• Number of antral follicles (early follicular phase)
• Low numbers of antral follicles - sign of DOR and
observable earlier than a rise in FSH serum level
• But - cycle–cycle variation
• Intra-observer variation
• AFC ~ AMH
• Scheffer et al Fertil Steril 1999
• Broekmans et al Fertil Steril March 2008 Epub
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14. Dr.Bharati Dhorepatil 14

15. • Prospective evaluation of automated follicle monitoring in
58 in vitro fertilization cycles: follicular volume as a new
indicator of oocyte maturity
• Conclusion(s)
• SonoAVC allows reliable evaluation of stimulated ovaries, and
may help us establish new criteria for timing hCG
administration based on follicular volume estimation rather
than follicular size. Software improvements are needed to
improve universal patient use.
• Fertility and Sterility
Volume 93, Issue 2 , Pages 616-620, 15 January 2010
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16. Dr.Bharati Dhorepatil 16

17. • Folliculogenesis
• Co-relation with endocrinology
• Ways of monitoring
• Tips to improve ovulation induction..
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18. Aim
• Monofollicular development
• Multifollicular..2 to 3
• Controlled Ovarian Hyperstimulatio
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19. Dr.Bharati Dhorepatil 19
Mono follicular Response…
Early follicular
Mid
Late Surge

20. Dr.Bharati Dhorepatil 20
2 to 3 follicle
Early follicular
Mid
Late Surge

21. COH
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Early follicular
Mid
Late Surge

22. Basic facts..
• Follicles are present in the ovary at different
stages of development, at any given point of
the menstrual cycle
• It is unknown as yet which factors regulate
initiation of growth of primordial follicle
• An increase in the number of granulosa cells is
critically important for the advancement in
developmental stages of the follicle.
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23. • Stimulation by FSH is an absolute requirement for
development of large antral preovulatory follicles.
Duration and magnitude of FSH stimulation will
determine the number of follicles with augmented
aromatase enzyme activity and subsequent E2
biosynthesis.
• High FSH levels usually occurring during the luteo-
follicular transition give rise to continued growth of a
limited number (cohort) of follicles.
• Subsequent development of this cohort during the
follicular phase becomes dependent on continued
stimulation by gonadotropins.
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24. • The entry of FSH into follicular fluid at
cavitation is believed to provide the induction
stimulus that initiates the process of graafian
follicle growth and development.
• At the cellular level, it is the FSH receptor on
the granulosa cell that is the fundamental
player in this process.
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25. FSH Threshold & Window
FSH Threshold and Recruitment Window
Threshold
Window
Rekruitment Selection Dominance
The longer and higher FSH is above threshold the more follicles are recruitet
Atresia
The longer and higher FSH is above threshold the more follicles are recruitet.
Fauser and Heusden, Endocrine Rev. 1997; 18; 71-106
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26. Protocols….
1. CC.
2. Enclomiphene..step up,extended
3. CC ± FSH or ± HMG.
4. Gn. Standard step-up protocol.
5. Gn. Low dose step-up protocol.
6. Gn. Low dose step-up, step-down
protocol.
7. Adjuvants
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27. Gonadotrophins..
• Conventional
• Low dose protocol
• Chronic Low dose Protocol
• Chronic step up AND step down protocol
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28. • The goal of folliculogenesis is to produce a single
or multiple dominant follicles from a pool of
growing follicles…
Four major regulatory events :
• Recruitment
• Follicle development
• Selection,
• Surge (maturity)
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29. Role of FSH and LH
• Both FSH and LH are required for promoting follicular
growth and differentiation…
• FSH..principal stimulator and regulator of
antral follicular growth…
• Some LH ..preantral stage..to stimulate
secretion of androgens by thecal cells…then
mid follicular phase to nourish..
then late follicular phase for surge
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30. Follicular monitoring..Basic Cycle Profile
Pivotal Scan…D2 or D3
• Both Ovaries…AFC, residual cyst
• Endometrium…Complete Shedding
D10 to D14..Pre ovulatory Scan
D20-21…Luteal Scan
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31. What to achieve before ovulation?
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32. Ovulation Monitoring
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33. Monitoring starts..
• D7,D8,D9…any day could be a start
• Growth pattern to be followed..Day X 2mm
appro.
• Alternate day monitoring is advisable if
required changed according to the need
• Sustained growth…is must
In healthy follicles, genes direct
cytodifferentiation, proliferation, and follicular
fluid formation.
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34. Ovulation Monitoring
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35. • The most striking change in LH secretion
occurs at the end of the follicular phase, when
there is an abrupt rise in its concentration.
• This is the preovulatory gonadotropin surge
that initiates the ovulatory process.
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36. Timing of events..
LH surge:
• 0hr…….GV with nucleolus
• +15 hours………… GVBD
• +20 hours………… first meiotic metaphase
• +35 hours………… second meiotic metaphase
• +38 hours………… ovulation
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37. • The large increase in LH inhibits androgen
production, and as a result estradiol
concentrations decrease drastically from the
preovulatory peak.
• Granulosa cells become 'luteinized', and
consequently a small preovulatory rise in
progesterone occurs within one hour of the LH
surge completion
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38. Recent advances..
• Assessment of the ovarian volume, number
and volume of follicles and
ovarian/perifollicular vascularity by three-
dimensional ultrasonography and power
Doppler angiography on the HCG day
• Computarised automated assesment of
follicular size
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39. Dr.Bharati Dhorepatil 39
•Assesment of the follicular maturity and endo receptivity
and the time of HCG Is one of the Key factors for the
success of all ART procedures
•Vascular changes are the reflection of the biochemical
changes.
•3D power doppler gives not only qualitative but also
quantitaive idea of the global vasularity
•Thus it is reflection of Functional/physiological maturity

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•Follicular vasularity distribution
and flow indices..
Better parameters of follicular
quality and can be guideline for
the time of HCG and IUI

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Vasularity grades…
1.<25%,
2.25to 50%,
3.50to75%,
4.>75% of follicular circumference
Conception rates are higher with Gr.III & IV
vasularity….
Chug et al

42. When to give HCG..
• Perifollicular and subendometrial Hallo…oedema
• Cumulus presence..30-40%
• Follicular volume..3-7ml
• Flow Indices…PSV>10,RI<0.5
• Perifollicular Vasularity..3/4th
• Sub Endo vasularity..minimum 5 spiral vessels
reaching to zone 4,ant &post,RI<0.6
• Endo peristalsis 3to5/ min
• Uterine A..on dominent sidePI<3.2
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43. Subendometrial Blood flow
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44. Endometerium
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45. Timeline of ovulation
• Case A..Day 11…DF..18mm,..endo..8mm,triple
line
• but RI<0.48,PSV 6-7,poor flow
Timeline…Wait…HCG next Day or when
parameters improves as PSV low
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46. • Case B…Day 10…DF 18-19mm,
Endo..7mm,triple line
• RI..<0.5,PSV >15, 85 % good
flow
• Timeline…Give HCG right away
as it is a sign of impending LH
surge ( LH surge starts UA PI is
v.high)
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47. • Case C..
• Day 11…DF..19.9mm,Endo 6.5mm
• PSV 7,RI>0.45,v.poor perifollicular flow
• Timeline…LUF..
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48. When one or two IUI
• Depends on PSV>25…just one IUI,no
trigger..with in 12 to 14hrs
• PSV<15…RI<0.5…Trigger comfortably..34 hrs
and 48hrs IUI
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49. Test..
• 29yr old, BMI 28,AFC 6,AMH 3ng/ml pt comes
with three cycles of CC 100mg taken with
TIC..with tubal patency,no male factor..D2 of
the menses..
• What Is your choice of gonadotropins
• What dose to start and maintenance
• When will be your first scan,what will you
expect?
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50. • 29yr old, BMI 34,AFC 20,AMH 10ng/ml pt
comes with three cycles of CC 100mg taken
with TIC..with tubal patency,no male
factor..D2 of the menses..
• What Is your choice of gonadotropins
• What dose to start and maintenance
• When will be your first scan,what will you
expect?
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51. Tips… successful ovulation Induction
• You are not doing Ovarian stimulation, but
• You are preparing egg from given ovary to get
pregnancy out of it..
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52. • Synchronus Follicular growth..small dose to start,early
follicular phase recruitment, small incremental dose
• Critical time of trigger for adequate LH surge
• Appropriate Choice of Injection for stimulation &
trigger
• Right amount of doses
• Avoid Premature LH surge & leutinization
• Constant look for endometrial quality development to
have good functioning endo for implantaion
• Appropriate and right amount of luteal support
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53. • The production of a viable embryo requires
ovulation of a competent oocyte, adequate
progesterone production by the CL, and an
adequate uterine environment.
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54. • Evidence may change with more trials:
concepts to be kept in mind.
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55. Learn from yesterday,
live for today,
hope for tomorrow
The important thing is…not to stop questioning
Albert Einstein
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56. • Three theories of follicle recruitment have
been postulated to date:
• (i) the ‘continuous recruitment’ theory,
• (ii) the ‘single recruitment episode’ theory
and
• (iii) the ‘wave’ theory.

57. • to treat poor prognosis or oncological patients
through
• Duostim,
• LPS-only or
• random-start ovarian stimulation approaches.

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