Cumulative pregnancy is a key strategy to optimize success in ART.

1. Prof. Rokeya Begum
Director
Surgiscope fertility center
&
Honorary Adviser
USTC
Bangladesh.
HOW TO OPTIMIZE
ART OUTCOME

2. Success of
ART is
compartmentalized
Couple
Stimulation
protocol
LabEmbryologist
Clinician

3. Selection of Patient
Age
Nutritional status
Lifestyle
Psychological factor
Medical H/O
Reproduction H/O
Family history
Risk
variable

4. Fertility is decreased by half in woman in their late 30s
compared with woman in their early 20s.
IVF cannot reverse the effect of age on fertility .
Age
Live birth rate following IVF diminish by
2% for each year of female age.

5. Maternal age is a strong
independent factor for
increase in outcome of
IVF.

6.  Decline in male fertility
 Increase risk of genetic mutation
 Autism related disorder after age of
45-50 years.
Advanced
Paternal Age

7. Life style
Weight
Obesity
-BMI  30kg/m2
under weight
-BMI  18kg/m2
Both obesity and under
weight are associated with
decline fertility through chronic
anovulation.
Why
 Reduced responsiveness to
stimulation protocol.
 Higher cycle cancellation rate.
 Embyo quality.
 Impaired embyo implantation
rate.
 Particularly abdominal adiposity.

8. Pregnancy rate decreases by
30% per cycle for each 0.1
increase in waist/hip ratio.
In men obesity
• Abnormal sperm count.>35kg/m2
• Higher DNA fragmentation.

9. Pathogenic mechanisms
- Increase testicular temp due to fat deposition.
- Decrease in circulatory testosterone due to sleep apnea.
- Hyper insulinaemia.
- Dysregulation of HPO by increased oestrogen.

10. Smoking
All couples should be counsel
to avoid smoking and to
eliminate exposure to passive
smoking.

11. Alcohol
All woman should be assessed for alcohol use and
advised of the risks to fertility and to the fetus. Woman
should be informed that there is no safe level of
alcohol exposure in pregnancy.
Alcohol Causes :
- Anovulation
- Impaired implantation
- Reduced libido
- Impotency
- Abnormal sperm parameter

12. Psychosocial
stress
In Women -
1. Lower number of oocyte retrieval
2. Lower implantation
3. Lower pregnancy rate
In Men –
Stress -  testosterone
 spermatogenesis

13. Immunization
The assessment of the woman’s vaccinations
history is strongest recommended before
beginning the treatment of infertility.

14.  Autosomal recessive disease –
carriers are asymptomatic.
 Thalassemia
- use of donor gametes
- pre implantation genetic diagnosis
Genetic counseling

15. Adverse outcomes in previous pregnancies –
1. Counsel regarding recurrence of another event .
2. Preventive strategies –
Repeat miscarriages, still birth or preterm
delivery necessitate work up to identifies the
cause.
Reproduction history

16. Chronic medical conditions
Maternal fetal medicine specialized involved
to care these woman in pre conceptional
stage.
For majority of chronic disease optimal
control prior to ART for favorable maternal
and neonatal outcome.

17. High risk for pregnancy
 pulmonary HTN
 Eisenmenger’s syndrome
 Marfans syndrome, with aortic involvement.
 Severe renal insufficiently.

18. Screening for
infections disease
before
ART.

19. Men are active
partners in ART
Undergo medical evaluation
before ART in order to detect
and modify high risk
behaviors and poorly
controlled diseases.

20. Pelvic pathology is detrimental
to
IVF outcome.

21. Uterine fibroids
Uterine fibroids occur in upto 30% of
reproduction age women.
(Verkaut 1992)

22. 1.Submucous fibroid is essential to remove before IVF.
2. Sub serious fibroid should be ignored.
3. There are no studies to confirm the value of
removing intramural fibroids.
However there is evidence to suggest a benefit after
removing them.
Treatment
Fibroid

23. Hydrosalpinx which are visualized by
USG reduced IVF outcome and should be
removed.
As an alternative cornual ligation could
be done.
Hydrosalpinx

24. Surgical management of endometriomas has no
significant effect on IVF pregnancy rates and
ovarian response to stimulation.
Endometrioma
Fewer oocytes were retrieved.
Endometrioma effect oocyte number
but not embryo quality or pregnancy
outcome, irrespective of the presence of
an ovarian endometrioma.

25. .
Uterine septum
Removed of uterine
septum may improve
the IVF outcome

26. Sharam et al (1997) recommended that all
couples with elevated titers of chlamedia
trachomatis IgG antibodies be treated with
Doxycycline prior to IVF.
Pelvic infection before IVF

27. IVF patient with bacterial
vaginosis have decreased
conception rates and increased rate
of early pregnancy loss.

28. Ovarian stimulation
There is a strong association between
the number of oocytes retrieved and
live birth rates in IVF.

29.  The optimum number of oocytes needed to
maximize IVF outcomes seems to be about 15.
 COS should be tailored to individualized.
Maximum – for poor responder
Fine tuning for – Hyper responder

30.  Young and older patients
 Polycystic ovaries/PCOS
 High basal FSH/small ovaries
 Previous OHSS/poor response
Easily
Recognized
Who is Who in ART

31. AMH and AFC are currently
the best tools to predict ovarian
response .
BIOMARKERS of
Ovarian Response

32. Gonadotrophin
preparation and oocyte
yield.

33. Gonadotropin Preparations
and
Oocyte Yield

34. Rec hFSH has greater
potency compared to
both HMG and HP
HMG.

35. Protein
content
Specific activity
(IU/mg protein)
Injected
protein per
75 IU (mcg)
hMG < 5% ~100 ~750
hMG-HP < 70% 2,000–2,500 ~33
rec-hFSH* > 99% 13,645 6.1
Size Exclusion
High
Performance
Liquid
Chromatograph
y (SE- HPLC)
Protein content in solution
bymass (FbM)

36. Higher FSH bioactivity, which is related to
the way the drug is made, filled and delivered.

37. Accurate dose delivery
Adjustments by small
increments Self-administration
25%
Folitropin alfa prefilled
ready-to- use
pen
Needle-free
reconstitution,
conventional syringe
Easy of use 58%
Dosing mechanism 43%
Less chance of error 26%
75%

38. GnRh
Antagonist in
High
Responders
LH Trigger with
GnRH agonist in
high responders.

39. GnRH Antagonists
in
High Responders
9 RCT; 966 PCOS women
GnRH Antagonist X Agonist
Weight Mean Difference (WMD)1; Relative
Risk (RR)2
Duration of stimulation -0.74 (95% CI: -1.12; -0.36)1
Gonadotropin dose -0.28 (95% CI: -0.43; -0.13)1
Oocytes retrieved 0.01 (95% CI: -0.24; 0.26)1
20% vs 32%
Risk of OHSS (Moderate & Severe) 0.59 (95% CI: 0.45-0.76)2
Clinical PR 1.01 (95% CI: 0.88; 1.15)2
Miscarriage rate 0.79 (95% CI: 0.49; 1.28)2

40. LH Trigger with GnRH
agonist in high responders.

41. Intervention Outcome Evidence
Ovarian biomarkers Identify who are at risk 1a
Recombinant rather than urinary
gonadotropins
Oocyte yield 1a
Biomarkers + low starting doses of rec-
hFSH FbM
Fine-tune COS + oocyte
yield
1b
GnRH Antagonists OHSS 1a
GnRH Agonist for LH Triggering OHSS 1a
Two-step IVF OHSS 1b
Evidence-based Strategies to Optimize
COS in High Responders

42. Impaired Oocyte Quality
Reduced Fertilization Rate
Reduced Embryo Quality
Increased Miscarriage Rates
Ovarian Aging

43. Intervention Outcome Evidence
Ovarian biomarkers Identify who are at risk 1a
Recombinant rather than urinary
gonadotropin
Oocyte yield 1a
Adjuvant therapy Pregnancy rate 1a
GnRH antagonist protocol Duration of stimulation 1a
LH supplementation Pregnancy rate 1a
Biomarkers + rec-LH Oocyte yield/cancellation/PR 2a
LH supplementation with rec-LH
rather than hMG
Pregnancy rate 2a
Evidence-based Strategies to Optimize COS
in Poor Responders

44. Laboratory technique
and procedure.

45. Culture media
Sequential – where embryos are
moved part way through the
culture period to a medium with a
different composition.
Single step – Embryo are held in
the same dish throughout and
culture medium is not
replenished any point.

46. Single step media – is advantageous
when used in conjunction with
continuous embryo monitoring
system.
This minimizes –
 stress to embryo
 change in PH
 Light
 Temp outside the incubator

47. Continuous embryo
monitoring through time-
lapse technology by
use of single step culture.

48. Cryopreservation
Cryopreservation which is mostly used to
preserve surplus embryos and cryopreserve
donoted gamates or embryo for future cycles.

49. Cryopreservation
Vitrification
 Slow cooling

50. Vitrification achieves higher
survival rates than slow cooling.

51. 1. Avoid the formation of ice crystals during the
freezing process.
2. Intracelluler crystal formations creates lethal
factors through unwanted physical and chemical
events that may injure the cell during the
cryopreservation process.
The most important principle of
cryopreserving oocytes and embryos

52. 1. No mechanical injury
2. Less osmotic stress to cells.
3. No intracellular crystal formation.
4. Less labor in laboratory daily work.
5. Simple protocol.
6. Useful for oocytes and blastocyst which have less
success with slow freezing.
7. No need for expensive devices.
Why do to prefer the Vitrification
procedure now ?

53. Fresh embryo transfers can be
replaced by cryopreserved – thawed
embryo transfers in ART cycles.
COH has been shown to
advance endometrial
maturation and adversely
affects implantation in
ART.
There is a better embryo-
endometrium synchrony in
frozen-Thawed embryo
transfer cycles than fresh
embryo transfer cycles.

54. Freeze all cycle – safer approach to
eliminate risk of hyper stimulation
with at least equivalent results and
better obstetric and perinatal
outcome versus fresh embryo prefer.

55.  Embryo grading has been proposed
as the most appropriate system for
selecting the best embryo.
 Assessment of morphological
characteristics is an easy and non
invasive way.
Selection of embryo

56.  Preimplantation genetic screening (PGS).
 Age more than 40 yrs -
- Risk of trisomy
- Risk of miscarriage
 RIF (Repeated Implantation Failure).
 Recurrent Miscarriage
 Male Infertility
Technique to assess embryo
quality

57. PROS
- Time to pregnancy decrease
- Decreased risk of miscarriage
CONS
- More RCTs required
- Embryo may be autocorrect
- Mosaicsm : confusing the issue
of transfer

58. No of embryo transfer
Single embryo transfer
VS
Multiple embryo.

59. Faced with the prospect of never giving birth, women
were willing to accept a significantly greater risk of
experiencing the worst perinatal outcome.
Perinatal death was valued significantly lower than
treatment failure (P values < 0.001) .
All disability outcome were valued significantly higher
than the no birth outcome (all P values < 0.001).

60. Techniques and technology for
Embryo transfer
Parameters affecting ET outcomes
1. Anatomy
- Uterine position
- Utero cervical angle
- Bacterial inoculation
- Uterine contraction
2.Technique
- catheter guidance
- catheter tip location
- injection mode

61. 3. Catheter
- Soft versus firm
- Internal diameter
- Tip shape
4.Transfer medium
- Medium/Air volume
- Viscosity
- Adherence compounds

62. ET practices with supported
proof benefit
 Use of soft embryo catheters
 Ultrasound guidance

63. 1. Mid uterine position of catheter tip.
2. Mechanical closure of the cervical canal following ET.
3. Acupuncture during ET
4. Use of hyaluronic acid during ET
5. Shortening of the loading discharging interval time of embryos.
ET practices with Limited proof
benefit

64. 1. Use of mock transfer.
2. Full bladder during ET.
3. Use of cervical tenaculum.
4. Removal or flushing of cervical mucus.
5. Antibiotic administration during ET.
6 .Bed rest following ET.
7 Use of fibrin sealants during ET.
ET practices with no proof
benefit

65. Human endometrium
–The last challenge

66. Strategies for improving endometrial
receptivity
To develop ovarian stimulation protocols-
minimal reduction of receptivity or increase it.
To avoid the endometrium during stimulated
cycle- Freezing the embryo and replacing in
subsequent natural cycles.
To increase uterine vascularity- Low dose
aspirin, L-arginine, Sildenafil.
To treat the uterine pathology.
5.Local injury stimulates the endometrium.

67. Luteal phase support
Corpus luteum
A major source of steroid
hormone and secretes
progesterone upto 40mg/day. LPS is definitely
indicated in IVF
treatment cycle.

68. When to start progesterone
Day of OPU
How long
Debatable
1. Upto 8weeks or 12 weeks
2. Upto 1st ultrasound scan
3.Upto establishing pregnancy

69. What is the route
1.Oral-micronised 600-800mg/day in a divided dose.
2.Vaginal/ Rectal- micronised 600-800mg/day in a
divided dose.
3. I/M 50-100mg/day
4. S/C Aqueous 25mg/day
5. Dydrogesterone-10mg twice daily
6. Gel 8%-90 mg once daily

70. No evidence favoring a
specific route or duration of
administration of progesterone.

71. Maximize Beneficial
Effects
Minimize Complications and Risks
Cycle
Cancellation
Multiple
Pregnancy
OHSS
Failure
Singleton live
birth at term

72. Cumulative pregnancy is
a key strategy to
optimize success in ART.

73. Prof. Syeda Nurjahan Bhuiyan