8. Hysdrosalpinx
• TVUS aspiration of hydrosalpinx (at time of
oocyte retrieval)(Hammadieh et al, 2008
• Salpingectomy or tubal disconnection has
been proved to improve pregnancy rate in
case of VISIBLE hydrosalpinx by U/S
18. OHSS is the most serious complication
of ovulation induction.
19. Protocols for IVF
GnRH Antagonist
Protocols
GnRH Agonist
Protocols
225 IU per day
(150 IU Europe)
Individualized Dosing of FSH/HMG
250 mg per day antagonist
Individualized Dosing of FSH/HMG
GnRHa 1.0 mg per day
up to 21 days
0.5 mg per day of GnRHa
225 IU per day
(150 IU Europe)
Day 6
of FSH/HMG
Day
of hCG
Day 1
of FSH/HMG
Day 6
of FSH/HMG
Day
of hCG
7 – 8 days
after estimated ovulation
Down regulation
Day 2 or 3
of menses
Day 1
FSH/HMG
20. (GnRH) antagonists: off label
indication
• unique Idea
• Administration during GnRH agonist cycle
• when follicle reach ~16mm and E2 level >
4000pmol
• Decrease but Continue hMG (step down
protocol)
• Monitor by E2
• Not more than 3 days
21. Long Protocol
GnRH agonist daily/depot
DAY 21
No Cyst
E2<200pmol/L
hCG
OPU
32-42h
6
FSH
1
≥3 follicles ≥16mm
and/or
E2 ≥1000 pmol/L / foll ≥16mm
22. Value
• allow continued stimulation while rapidly
decreasing the E2 level to a range that is
clinically acceptable.
25. Our Results
Parameter Coasting (n = 96) Antagonist (n = 94) P-value
Age (years) 30.0 ± 4.9 29.6 ± 4.6 NS
Duration of infertility (years) 6.64 ± 4.45 7.07 ± 4.3 NS
No. of HMG injections 30.52 ± 8.9 29.94 ± 8.8 NS
Days of stimulation1 9.1 ± 1.5 9.4 ± 1.5 NS
Peak oestradiol (pg/ml) 5087 ± 1589 5305 ± 1680 NS
Oestradiol on day of HCG (pg/ml) 2605 ± 790 2721 ± 699 NS
Range of oestradiol on day of HCG (pg/ml) 1110–4136 1223–4093 NS
Day of intervention 2.82 ± 0.97 1.74 ± 0.91 <0.0001
No. of oocytes 14.06 ± 5.20 16.5 ± 7.60 0.02
No. of MII oocytes 11.13 ± 4.60 13.14 ± 6.60 NS
No. of fertilized oocytes 7.97 ± 3.80 9.14 ± 4.70 NS
No. of high quality embryos 2.21 ± 1.10 2.87 ± 1.20 0.0001
No. of embryos transferred 2.83 ± 0.50 2.79 ± 0.40 NS
No. of cryopreserved embryos 4.50 ± 3.93 5.77 ± 4.87 NS
Clinical pregnancy (%) 46/96 (47.9) 52/94 (55.3) NS
Multiple pregnancy (%) 15/46 (32.6) 17/52 (32.7) NS
26. Intravenous Albumin to Prevent OHSS
• Cochrane review update (Al-Inany et al., 2011)
7 randomized controlled trials
Clear evidence of beneficial effect
27. Administration of human albumin might result
in :-
1. restoration of intravascular volume
2. Inactivation of the vasoactive intermediates
responsible for the pathogenesis of OHSS
5/23
28. Another Colloid
• Hydroxyethyl starch (HES) is a plasma
expander
• it avoids any potential concern about viral
transmission that may be present with
albumin
7/23
29. Results Of Search
31 studies
10 RCTs (n= 2048)
7 RCTs : HA vs. P 1 RCT : HES vs. P 2 RCTs :HA vs. HES vs. P
9/23
No RCTs compared dextran or haemaccel vs placebo
31. Cabergoline (Cb2) therapy
• Cb2 prevents VP in a dose dependent manner without affecting
angiogenesis and implantation in humans
• Cb2 reduced the amount of ascites, hemoconcentration and incidence of
moderate-severe OHSS5
• Cb2 0.5 mg x 8 days (total of 4 mgs) starting day of trigger
Alvarez, et al, Hum Reprod, 2007; 22: 3210-3214.
38. Poor responders: who are them ?
No standard definition or diagnostic criteria exist until now,
Expected :-
Retrospectively :
history of low ovarian response in their first IVF cycle
Prospectively :
basal day 3 FSH level > 10 IU/mL,
antral follicular count < 5 follicles
advanced women age ≥ 35 years
Unexpextantly :-
in young patient < 35 years with non elevated FSH level
which may reflect early ovarian aging .
40. Growth hormone
• Growth hormone may improve the number of
oocytes but no difference in pregnancy rate
• However, they are expensive and routine use
can not be justified
42. DHEA
• Rx DHEA 50 mg ½ tab BID (Belmar)
• Can decrease dose for SE, i.e. acne
• Optimal > 8 weeks prior to OPU
• stops med at hCG
43. Infection
• Vaginal antisepsis, negative effect
• < Quality of the oocytes and the embryos
• Bacterial contamination of the ET catheter tip
• But the problem:
• Which antibiotics: against gram –ve, or
anaerobic or gram +ve
• When to give : start of stimulation or around
OPU
• For how long???
44. Controversial role of antibiotics
• Ceftriaxone + metronidazole
• At oocyte recovery
– Reduction of bacteria on the
transfer catheter clip (78,4%)
– > CR
• 21,6 % vs. 9,3%
– > CPR
• 41,3% vs. 18,7%
– Egbase PE, Lancet 1999
• Amoxycillin + clavulanic acid
1g/1,25, RCT
• At oocyte recovery + 6 days
• > Pregnancy loss rate
– 33,3% vs. 20,8% (p=9,15)
• Not recommend this antibiotic
prescription *
• Ensure maximum catheter
sterility *
• Peikrishvili R, JGOBR 2004
46. Luteal E2
• No evidence of improvement in
pregnancy rates
Dragisic KG, et. al., Fertility and Sterility, Oct 05, 1023-6.
47. Assisted Hatching
• Routine assisted hatching is not
recommended because it has not been
shown to improve pregnancy rates
48. Sildenafil
– Vaginal sildenefil improves
uterine artey blood flow and
sonographic endometrial
appearence
• Sher G, HR 2000
• No evidence of effectiveness
49. Heparin
• Treatment of choice
– Recurrent pregnancy loss due to aPL antibodies
• Heparins are involved in activities anticoagulation and
adhesion of the blastocyst to the endometrial epithelium and
subsequent invasion
• aPL may be responsible
– < Phospholipid adhesion molecules of trophoblast
– < hCG release
– < Trophoblast invasiveness
– < Trophoblast differentiation in vitro
» Fiedler K, EJMR 2004, Di Sormone N, AR 2000
50. Heparin and success rates
• Assumption
– < Immunological status
– < Embryo implantation
• Seropositive women in IVF
– at least one aPL
• Heparin 5000 IU, Aspirin 100
mg daily
• NO significant difference in PR
those treated and those
receiving placebo
– Quenby S, FS 2005,
Stern C, FS 2003
• Seropositive women
– > 3 IVF failures
– at least 1 thrombophilic
defect
• Enoxaparin (Low molecular
weight heparin), 40 mg daily
• > CR,> PR, > LBR/ placebo
• 20,9% vs. 6,1%
• 31% vs. 9,6%
• 23,8% vs. 2,8%
» Qublasn H, HF 2008
51. Immunoglobulin (IgG)
• Indications
– > Embryo failure
– > Recurrent miscarriage
• > Inappropriate
immune response
• > Proinflammatory
cytokines
• Preparations of IgG contain
– All humoral IgG antibodies
– Normally in the plasma of
blood donors
• Effects of IgG:
– < Proinflammatory citokynes
– > Antinflammatory cytokines
– < NK cells
– < Pathological antibodies
• Dose:
– 500 mg iv / kg before ET
• Carp HJ, CRAI 2005
• Coulam CB, EP 2000
52. IgG before ET
• No improve in PR
• Stephenson MD, FS 2000
• No benefit
• Balasch J, FS 1996
• > LBR (SS), meta analysis,
3 RCT
• Clark DA, JARG 2006
• > PR (56% vs. 9%)
• Coulam CB, EP 2000
• > Outcomes in specific
group of IVF patients with
positive APA
• Sher G, AJRI 1996
54. Beneficial effects of acupuncture
• Timing of administration:
– During ovarian stimulation
– At oocyte recovery
– At ET and afterward
• A number of systemic reviews
and meta-analysis have been
conducted on its efectiveness
as an adjuvant treatment
• > CPR, > LBR
• Manheimer E, BMJ 2008
• > PR
– Ng EH, BJOG 2008
• > CPR, > LBR
• El-Toukhy T, BJOG 2008
• > LBR
• Placebo effect and small sample
size cannot be excluded *
• Not recommended as a routine
use procedure *
• Cheong YC, Cochrane database
Syst Rev 2008
55. Aspirin following ET
• Aspirin 75 mg
– Alternate days from
the day of ETuntil 18
days after retrieval
• Evaluation:
– Ovarian blood flow
– Folliculogenesis
– Ovarian
responsiveness
– Uterine vascularity
and receptiveness
• RCT of 1380 women
– LBR
• 27% (with aspirin)
• 23% (without aspirin)
– Waldenstroem U, FS 2004
• Low-dose aspirin does not
improve IVF outcome and it
cannot be recommended for
routine clinical use
– Revelli A, FS 2008; Duvan CL, JARG
2006; Fratarelli JL, FS 2008;
Gelbaya TA, HRU 2007
56. Glucocorticoids
• Immunomodulators
– > Intra uterine environment
– > Implantation rate
– < NK cells
– < Cytokines
– < Endometrial inflammation
– Boomsma CM,
Cochrane Database Syst
Rev 2007
– Tetsuka M, JCEM 1997
– Miell JP, JE 1993
• > Ovarian response to
gonadotrophins
• Dexametasone
– => enzyme 11-beta
hydroxysteroid dehxdrogenase
type 1
– => Directly influence follicular
development
– => Indirectly by increasing
serum GH, IGF-1, and
consequently follicular fluid
IGF-1 levels