Effective interventions in ART An overview of Cochrane Reviews

2015

Aboubakr Elnashar Benha university Hospital, Egypt

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Searching for the Best Evidence

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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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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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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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Results

• Effective interventions:

indicating that the review found evidence of

effectiveness (or improved safety) for an

intervention.

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• Ineffective interventions:

indicating that the review found evidence of lack of

effectiveness (or reduced safety) for an

intervention.

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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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• 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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• 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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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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• 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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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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• 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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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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• 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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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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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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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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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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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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• 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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• 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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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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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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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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• 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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• 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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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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