This presentation discusses ovulation induction in different cases like Poor Ovarian reserve, Hypo-hypo, Unexplained & Ovarian failure

1. Ovulation Induction in Different Case Scenario
Dr. Kaberi Banerjee
Advance Fertility and Gynae Centre
Lajpat Nagar and Noida

2. Case A

3. • What is poor ovarian reserve?

4. Bologna Criteria
• Bologna criteria recommend the presence of at least two of the
following three features for diagnosis of POR:
• Advanced maternal age (≥40 years) or any other risk factor for POR
• A previous POR (≤three oocytes with a conventional stimulation
protocol)
• An abnormal ORT (i.e. AFC, 5–7 follicles or AMH, 0.5–1.1 ng/ml).

5. • What is Poseidon Criteria ?

6. POSEIDON (Patient Oriented Strategies Encompassing
Individualized Oocyte Numbers)

7. • Patient X aged 38 years visits the OPD with primary infertility 7 years.
Her menstrual length is 24 days. She has had 3 failed IUIs . Husband
semen analysis is normal.
• What investigations will you ask for?

8. • AMH – 0.9 ng/ml
• TVS
• AFC -4 (rest nad)

9. • Gonadotrophin type?
• Dose?
• Protocol?
• Adjuvant?

10. Natural Cycle
It is based on the concept that there ar
folliculogenesis which can occur throughou
not limited to day 2. Hence f rst stimula
in follicular phase and second one in the
Embryos are frozen, pooled and transfer
cycle. T ere was no dif erence in fertilizati
blastocyst rate, conf rming the safety in
oocytequalityof bothstimulations.13
T egre
of thisprotocol istheaccumulation of oocyte
cycleof stimulation,minimizingthetimein
beperformed.
Ovulation Trigger in Poor Responder
HCGtrigger for ovulation shouldbegiven w
smaller lead follicle of 16 mm in poor
Earlier ovulation trigger may improve n
quality of embryos
Conversion to IUIvs Proceeding t
Poor Responder
It hasbeen seen that if thereisonlyonefollicl
Gonadotropin – Natural cycle vs higher dose
gonadotropins
T ere are many regimes for natural cycle or mild/
minimal stimulation. T ese regimes came into practise
af er it was demonstrated by some studies that higher
doses of gonadotropins yield aneuploid embryos.
However,subsequently somestudieshavenot supported
thishypothesis.
1. Mimimal stimulation: Start with 100 mg
clomiphenefollowed by FSH on day 2,4,6 and then
daily. Antagonist started asindicated.
2. Augmented Natural cycle: Add 150 IU of FSH to
natural cycle.
It has been seen that results do not improve with
increasing dose beyond 300 IU of FSH. Natural
cycle was considered an option however if results are
compared apregnancy rateof not morethan 2.6. isseen
whereasastimulation with 300 IU showed apregnancy
rateof 11%with onecyclein PORwomen.11
Hence, it is
recommended that stimulation should bedonebut with
not morethan 300IU.

11. Luteal phase estrogen protocol

12. Flare protocol

13. Duo- Stim Protocol
Update 2013 Adams GP et al., J Reprod Fertil, 1992
14 20 26
waves in a menstrual cycle

14. DUOSTIM in low prognosis patients

15. Duo Stim Protocol

16. • A 32 year old with an AMH of 3ng/ml and AFC of 9 has undergone
ovarian stimulation with rec FSH 150 IU daily for 10 days.
• Her folliculogram on Day 10 indicates only 4 follicles more than 16
mm.
• What could have happened?

17. Differences between slow and hypo-response
Hypo-response Poor response
Etiologic factors LH over-inhibition
LHR, LH, FSHR
polymorphism
Decrease in ovarian reserve
Ovarian reserve (AFC, AMH) Normal Decreased
Relationship with age Not obvious related The incidence rate increases
with the increase of age
Previous history of ovarian
injuries
Not obvious related High risk factors
Therapeutic measures add LH activity drug Comprehensive management
regimen
Number of oocytes
Retrieved
Normal ≤3

18. Diagnosis standards of slow response in Asian-Pacific
consensus
On the 6th day of stimulation, there was no ovarian
follicle with a diameter of over 10 mm
(De Placido, et al., 2005)
On the 6th day of stimulation, the estrogen
concentration was less than 200 pg/ml
(Vuong, et al., 2004)
The ovarian follicular development was slow, and
within 3 days, the growth was less than 2 mm.
(De Placido, et al., 2005; Bosch, 2009; Pezzuto et al.,
2010)

21. • What therapeutic intervention will you contemplate?

22. • Add LH
• ?increase dose

23. • What is ART Calculator?

24. ART Calculator – Total no. of oocytes needed for one
Euploid embryo
• Age
• BMI
• Male factor
• AMH
• Young- 4-9
• Older- 12

25. Mean number of oocytes needed and age
<35 39-40 42-43
Euploidy rate 60%
1 euploid
blastocys
t
1 euploid
blastocys
t
1 euploid
blastocys
t
Euploidy rate 30% Euploidy rate 20%
2 blastocysts≤
4 fertilized
oocytes
≤
5 MII oocytes≤
6 COCs≤
Age
3 blastocysts≤
7 fertilized
oocytes
≤
9 MII oocytes≤
11 COCs≤
5 blastocysts≤
13 fertilized
oocytes
≤
16 MII oocytes≤
18 COCs≤

26. Adjuvants?
• GH
• LH
• DHEAS/ Testosterone

27. • One follicle?

29. Case B

30. • A 30 year old lady visits you at the oupatient clinic with history of
infertility for 4 years and hypomenorrhea.
• Her AMH is 0.9 ng/ml and her AFC is 5.
• Husband semen analysis is normal
• HSG shows a small uterine cavity and patent tubes.
What is your next step?

31. • FSH is .7IU/ml
• LH is .6 IU/ml
• Diagnosis?

32. • Hypogonadotropic Hypogonadism
• Causes?

33. Etiologies of Hypogonadotropic
Hypogonadism
Stress
Hyperprolactinemia
Pituitary lesions (tumor, granuloma, abscess)
Cushing syndrome
Drug use (opiates, alcohol abuse)
Anabolic steroids use
Severe or chronic illness
Pituitary irradiation, trauma or surgery
Iron overload
Kallmann syndrome
Idiopathic hypogonadotropic hypogonadism
Other genetic mutations
Prader Willi syndrome

34. • What is next step?
• How will you start ovulation induction?
• Will you prepare her?

35. • You have started her on HMG 75 IU for one week, there is no
response, What will you do next?
• After 14 days there are 2 follicles each sized 12 mm?
• How will you proceed?
• When will you do IUI?

36. • If a patient of Hypo Hypo is going in for IVF, what considerations will
you keep in mind?

37. • Is there any other way of OI in Hypothalamic amenorrhoea?

38. Pulsatile GnRH
•
They underwent one or more cycles of pulsatile GnRH, at a frequency of 90 minutes,
either by the intravenous or the subcutaneous route.
• An initial dose of 5 μg per pulse in the intravenous route was administered and of 15 μg
per pulse in the subcutaneous route.
• The treatment was monitored by regular dosing of gonadotropins, estradiol and
progesterone, and the development of follicles and ovulation was monitored by intra-
vaginal ultrasonography.
• All the patients had documented ovulation, after a mean of 17 days on pump
stimulation.
• Single ovulation occurred in 30 of 33 treatment cycles, irrespective of the route of
administration.
• Ovulation resulted in 10 pregnancies over 7 patients (2 pregnancies in 3 of them)
• Gomez et al Gynecol Endocrinol. 2017

39. Summary
• Prepare uterus
• HMG
• FSH/LH
• Step up, may need high dose
• Long stimulation
• May develop Hyperstimulation
• Pulsatile GnRH
• Luteal phase support
• Outcome similar to other factors

40. Case C

41. • Mrs M with 29 years old is complaining of irregular cycles and
infertility for the past 1.5 years.
• What could cause her irregular cycles?

42. Causes for irregular cycles:
PCOS.
Immature axis.
POI.
Excess exercise.
Over & underweight.
Endocrine disorders.
Eating disorders.
Stress.
Drugs.

43. • What is POI?

44. Premature ovarian insufficiency:
POI is a clinical syndrome defined by loss of ovarian activity before the age of 40
years.
POI is characterized by menstrual disturbance (amenorrhea or oligomenorrhea)
with raised gonadotropins and low estradiol.(FSH >40 IU/l, estradiol < 20pg/ml
AMH<0.5ng/ml)
Prevalence:
Prevalence is 1%. The incidence is approximately 1:1000 women before age 30,
1:250 at age 35, and 1:100 at age 40.
Approximately 10-28% of women with primary amenorrhea and 4-18% with
secondary amenorrhea have POI/POF.(US statistics)
• ESHRE Guideline: management of women with premature ovarian insufficiency; Human Reproduction, Volume 31, Issue 5, 1 May 2016, Pages 926–937

45. • What are some differences of POI and PCOS?

46. PCOS VS POI
Criteria PCOS POI
Menstrual history Irregular cycles. Oligomenorrhea
Amenorrhea
Irregular cycles. Oligomenorrhea
Amenorrhea
Family history Present Familial POI is 29%
FMRI premutation.
Physical characters Evidence of hyperandrogenism.
Obesity, Hirsutism.
No evidence of hyperandrogenism
Sex hormones LH:FSH > 2:1.Level of hormones may be
in normal range.Serum Testasterone
raised.
FSH> 40 IU/ml
Estrasdiol < 20pg/ml
AMH<0.5 ng/ml
Inheritance Autosomal dominance inheritance. Autosomal dominant inheritance ( risk 50%)
X-linked inheritance and paternal
transmission.( risk 100%)

47. • What other investigations are needed in a case of POI?

48. Work up and Evaluation of POI:
Repeat serum FSH & estradiol after one month to confirm the diagnosis.
Low Estradiol (<50pg/ml) indicates hypoestrogenism.
Investigation Rationale
Pregnancy test –urine, serum To exclude pregnancy.
Serum FSH Hypergonadotrophic hypogonadism.
Karyotyping, FMRI premutation Common genetic problems.
TSH, Anti TPO Autoimmune thyroid dysfunction.
21 hydroxylase antibody Adrenal antibodies.
Ultrasound examination Ovarian reserve assessment.
DEXA Bone mineral density.

49. • How do you counsel a lady with POI who wants to conceive?

50. Infertility & POI management:
Counseling:
• Spontaneous ovulation occurs in 25% of these women.
• 5-10% of women with POI will conceive.
• Pregnancy and the conceptus will not bear any additional risk.
• Women with POI with chromosomal aberrations (XO) or single gene defects
(FMR1 permutation carrier) should have detailed counseling regarding the
problem of miscarriage and risk to the offspring.

51. POI and infertility: Available options:
• Waiting for spontaneous conception. (5-10% will have spontaneous conception)
• Not to have a child.
• Adoption
• Oocyte donation (endocrinological health to be assessed).
• Embryo donation
Treatment:
IVF with donor egg has better results.
Couple may decide for adoption.
Cryopreservation of oocyte, embryo or ovarian tissue.
In vitro activation an auto transplantation of ovarian tissue.
(under research).

52. Question:
What are the long term implications of POI?

53. Long term implications:
Osteoporosis.
Cardiovascular problems(endothelial
dysfunction, autonomic dysfunction,abnormal lipid profile,
insulin action disturbances and metabolic syndrome).
Urogenital atrophy.
Neurocognitive disabilities.
Shortened life expectancy
Endocrine problems.
Immunological problems(Myasthenia gravis, rheumatoid arthritis, and SLE).
Premature ovarian insufficiency: the context of long-term effects
J Endocrinol Invest. 2016; 39: 983–990

54. Concluding Remarks!

55. When IUI?

56. Factors determining Success of IUI

57. F

58. Advance Fertility & Gyne Centre
6-Ring road, Lajpatnagar, Delhi
9871250235, 9910176228
Advance Fertility & Gyne Centre
D-4, Sector 20, Noida, UP
9650683241, 8130322972