This document summarizes the key findings from 95 Cochrane systematic reviews on interventions for assisted reproductive technology published up to July 2015. 32 reviews identified interventions that were effective (19 interventions) or promising (13 interventions) in improving live birth or pregnancy rates. 14 reviews found interventions that were ineffective (2 interventions) or possibly ineffective (12 interventions). The reviews assessed interventions for various steps of ART including pre-ART strategies, ovarian stimulation, embryo transfer, and luteal phase support. Effective interventions included use of growth hormone, metformin, endometrial injury, and single embryo transfer. Ineffective interventions included follicular flushing and preimplantation genetic screening.

1. Effective interventions in ART
An overview of Cochrane Reviews
2015
Aboubakr Elnashar
Benha university Hospital, Egypt
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2. Searching for the Best Evidence
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3. The Cochrane Collaboration
 International collaboration
 Prepares, maintains, and disseminates systematic
reviews
 Diverse internal structure (Review Groups,
Centres, Fields, Methods Groups, the Consumer
Network)
Cochrane Library
 The current resource with the highest methodological
rigor
 $235/year or abstracts only
 www.cochrane.org
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4. Increasingly, couples are turning to ART for help
with conceiving and ultimately giving birth to a
healthy live baby of their own.
Fertility treatments are complex, and each ART
cycle consists of several steps. If one of the steps is
incorrectly applied, the stakes are high as
conception may not occur.
With this in mind, it is important that each step of
the ART cycle is supported by good evidence from
well-designed studies.
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5. 95 systematic reviews published in The
Cochrane Library up to July 2015 were
included.
All were high quality.
32 reviews identified interventions that were
effective (n = 19) or promising (n = 13)
14 reviews identified interventions that were
either ineffective (n = 2) or possibly ineffective
(n = 12)
13 reviews were unable to draw conclusions
due to lack of evidence.
(Farquhar et al, 2015)
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6. Results
• Effective interventions:
indicating that the review found evidence of
effectiveness (or improved safety) for an
intervention.
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7. • Ineffective interventions:
indicating that the review found evidence of lack of
effectiveness (or reduced safety) for an
intervention.
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8. 1. Pre-ART and adjuvant strategies
Effective interventions
• Endometrial injury in women undergoing ART:
performed in the month prior to ovulation induction:
increase both LBR or OPR and CPR
(moderate quality evidence).
•No evidence of a difference between the groups in
miscarriage, multiple pregnancy or bleeding rates.
•Endometrial injury on the day of OR: lower LBR or
OPL
(low quality evidence).
(Nastri , 2015)
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9. • Growth hormone for IVF:
in poor responders: significant improvement in LBR
(moderate quality evidence).
(Duffy 2010)
• Metformin treatment before and during IVF or
ICSI in women with PCOS:
No conclusive evidence for improved LBR
(low quality evidence).
Met increased CPR and decreased risk of OHSS
(moderate quality evidence).
(Tso, 2014)
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10. • Surgical treatment for hydrosalpix:
laparoscopic tubal occlusion is an alternative to
laparoscopic salpingectomy in improving IVF PR
(moderate quality evidence).
(Johnson, 2010)
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11. 2. Down-regulation with agonists or antagonists
Effective interventions
• GnRHa protocols for pituitary suppression in ART:
CPR was higher when GnRHa was used in a long
protocol as compared to a short or ultra-short
protocol
(low quality evidence).
(Maheshwari 2011)
• GnRHan for ART:
Antagonist compared with long GnRHa protocols:
reduction in OHSS
No evidence of a difference in LBR
(moderate quality evidence).
(Al-Inany 2011)
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12. • Long-term pituitary down-regulation before IVF for
women with endometriosis:
GnRHa for a period of 3-6 months prior to IVF or
ICSI: increased CPR
(very low quality evidence).
(Sallam, 2006)
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13. 3. Ovarian stimulation
Effective interventions
• Rec vs urinary gonadotrophin for ovarian
stimulation in ART:
all available gonadotrophins were equally effective
and safe.
Choice will depend upon:
availability of the product
convenience of its use
associated costs.
Any specific differences are likely to be too small to
justify further research
(high quality evidence).
(van Wely 2011)
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14. • Long-acting FSH vs daily FSH for ART:
medium dose (150 to 180 μg) of long-acting FSH
appeared to be a safe and as effective as daily FSH
in women with unexplained subfertility.
low dose (60 to 120 μg) of long-acting FSH
compared to daily FSH: Reduced LBR
(moderate quality evidence).
(Pouwer, 2015)
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15. 4. Ovulation triggering
Effective interventions
• Rec Vs. u hCG for final oocyte maturation
triggering in IVF and ICSI cycles:
u hCG remains the best choice for final oocyte
maturation triggering in ART
{availability and cost}
(moderate quality evidence).
(Youssef, 2011)
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16. • GnRHa Vs. hCG for oocyte triggering in
antagonist ART cycles:
GnRHa:
lower LBR
reduced OPR
higher miscarriage rate
reduction in OHSS rates
A trade off between benefits and harms (moderate
quality evidence).
(Youssef , 2014)
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17. 5. Oocyte retrieval
Effective interventions
• Pain relief:
5 different categories of conscious sedation and
analgesia appeared to be acceptable and were
associated with a high degree of satisfaction in
women.
The optimal method may be individualised
depending on
preferences of the women and their clinicians
resource availability
(very low quality evidence).
(Kwan , 2013)
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18. Ineffective interventions
• Follicular flushing:
No improved C or OPR
No increase in oocyte yield.
Increase operative time
More opiate analgesia
(moderate quality evidence).
(Wongtra-ngan 2010)
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19. 6. Laboratory phase
Effective interventions
• Low oxygen concentrations for embryo culture in
ART:
:an increase in LBR
(moderate quality evidence).
(Bontekoe , 2012)
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20. Ineffective interventions
• Preimplantation genetic screening for abnormal
number of chromosomes (aneuploidies):
using fluorescent in situ hybridization significantly
decreased LBR in women of advanced maternal
age and those with repeated IVF failure
Trials in which PGS was offered to women with a
good prognosis suggested similar outcomes
(moderate quality evidence).
(Twisk, 2006)
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21. 7. Embryo transfer
Effective interventions
• Ultrasound versus ’clinical touch’ for catheter
guidance:
significant increase in CPR
(low quality evidence).
(Brown, 2010)
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22. • Adherence compounds in ET media for ART:
use of hyaluronic acid.
improved LBR and CPR with the
Increase Multiple pregnancy rates
(moderate quality evidence).
(Bontekoe, 2014)
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23. • Number of embryos for transfer:
single embryo transfer compared with double
embryo transfer
 LBR was lower
 fewer multiple pregnancies
(high quality evidence).
cumulative LBR associated with single embryo
transfer followed by a single frozen and thawed ET
was comparable with that after one cycle of double
embryo transfer
(low quality evidence).
(Pandian, 2013)
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24. 8. Luteal phase support
Effective interventions
• LPS:
Progesterone appears to be the best method,
higher LBR and OPR than placebo
lower rates of OHSS than hCG.
Addition of one or more doses of GnRHa to
progesterone:
higher LBR and OPR than progesterone alone.
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25. Addition of oestrogen or hCG did not improve
outcomes, and hCG was associated with higher risk
of OHSS.
The route of progesterone administration did not
seem to matter
(quality of evidence low for most comparisons).
(van der Linden, 2015)
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26. 9. Prevention of OHSS
Effective interventions
•hydroxyethyl starch
decreased the incidence of severe OHSS
(very low quality evidence)
(Youssef 2011)
• Cabergoline:
reduce the risk of OHSS in high risk women,
especially for moderate OHSS
did not affect CPR or miscarriage rates
No increased risk of other adverse events
(low quality evidence).
(Tang, 2012)
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27. • GnRHan compared with long GnRHa protocols:
reduction in OHSS
no evidence of a difference in LBR
(moderate quality evidence).
(Al-Inany, 2011)
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28. • GnRHa versus hCG for oocyte triggering in
antagonist ART cycles:
lower LBR
reduced OPR
higher miscarriage rate
reduction in OHSS rates
a trade off between benefits and harms
(moderate quality evidence).
(Youssef , 2014)
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29. C O N C L U S I O N S
This overview provides the most up to date
evidence on ART cycles from systematic reviews of
RCT
Fertility treatments are costly and the stakes are
high.
Best practice requires using the best available
evidence to optimise outcomes.
The evidence from this overview could be used to
develop clinical practice guidelines and protocols for
use in daily clinical practice, in order to improve
LBR and reduce rates of multiple pregnancy, cycle
cancellation and OHSS.
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