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Cochrane Database of Systematic Reviews

Intervenciones para la prevención del SHEO en los ciclos de TRA: una revisión global de revisiones Cochrane

Información

DOI:
https://doi.org/10.1002/14651858.CD012103.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 23 enero 2017see what's new
Tipo:
  1. Overview
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Ginecología y fertilidad

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Selma Mourad

    Correspondencia a: Radboud University Medical Centre, Nijmegen, Netherlands

    [email protected]

  • Julie Brown

    Liggins Institute, The University of Auckland, Auckland, New Zealand

  • Cindy Farquhar

    Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

Contributions of authors

SM drafted first versions of the protocol and overview manuscripts. All three overview authors (SM, JB, CF) contributed to preparation of the protocol, data extraction and analysis of reviews for this overview. JB and CF contributed to the definitive version of the manuscript.

Sources of support

Internal sources

  • Department of Obstetrics and Gynaecology, University of Auckland, New Zealand.

    This department provided infrastructure support.

External sources

  • None, Other.

Declarations of interest

All three overview authors (SM, JB,CF) were co‐review authors on several of the included reviews. CF is a director/shareholder of a small day stay surgical unit and gynaecology clinic and undertakes private practice within these facilities. She has received travel/accommodation/meeting expenses from ESHRE or ASRM for attendance at scientific meetings. She does not receive any industry or commercial payments for research or travel. SM and JB report no conflicts of interest regarding industry.

Acknowledgements

Managing editor of the CGF Group Helen Nagels for helping with identification of registered titles and submitted protocols, and editor Jane Marjoribanks for reviewing and editing the protocol.

Version history

Published

Title

Stage

Authors

Version

2017 Jan 23

Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews

Review

Selma Mourad, Julie Brown, Cindy Farquhar

https://doi.org/10.1002/14651858.CD012103.pub2

2016 Feb 26

Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews

Protocol

Selma Mourad, Julie Brown, Cindy Farquhar

https://doi.org/10.1002/14651858.CD012103

Keywords

MeSH

Flow diagram of included reviews.
Figuras y tablas -
Figure 1

Flow diagram of included reviews.

Extent of effect of interventions on OHSS rate and live birth rate (when reported) or clinical pregnancy: OR and 95% CI.
Figuras y tablas -
Figure 2

Extent of effect of interventions on OHSS rate and live birth rate (when reported) or clinical pregnancy: OR and 95% CI.

Table 1. Review characteristics

Review ID

Number of included trials

Population

Definition of high risk for OHSS (where applicable)

Intervention

Comparison intervention/control

Primary outcomesa

Review limitations

ADA563

D'Angelo 2011

Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome

4 RCTs

340 women with PCOS

downregulated by GnRHa, undergoing superovulation in IVF or ICSI cycles

High risk: women with PCOS

Coasting when

oestradiol levels were > 2500 pg/mL or > 9000 pmol/L

Early unilateral follicular

aspiration

No coasting or other interventions

OHSSa

Live birtha

Clinical pregnancy

Number of oocytes retrieved

Multiple pregnancy

Miscarriage

Comparisons based on limited trial data

Live birth reported in only 1 trial

Trials lacked blinding, and half the trials lacked details on allocation concealment and incomplete outcome assessment

ADA561

D'Angelo 2007

Embryo freezing for preventing ovarian hyperstimulation syndrome

2 RCTs

151 women

downregulated by GnRHa, undergoing superovulation in IVF or ICSI cycles.

High risk: as defined by included studies

Cryopreservation

Fresh embryo transfer

Intravenous albumin

OHSSa

Clinical pregnancya

Live birth

Admissions

Evidence based on 2 trials, 1 for each comparison

Live birth reported in only 1 trial

Issues around methodological quality of both trials

TH1338

Tang 2016

Dopamine agonists for preventing ovarian hyperstimulation syndrome

16 RCTs

2091 women at high risk of developing OHSS undergoing ART

High risk: as defined by included studies

Cabergoline quinagolide, bromocriptine,

cabergoline + albumin,

cabergoline + HES

Placebo/no treatment/other treatment:

Albumin alone

HES

Coasting

Prednisolone

OHSSa

Live birtha

Clinical pregnancy

Adverse effects

Miscarriage

Multiple pregnancy

Allocation concealment and blinding not adequately reported.

One study used a co‐intervention of albumin IV and 1 of HES

Different regimens of cabergoline administration between included studies

Live birth rate reported in only 2 studies

Incomplete reporting of multiple pregnancy rate, adverse effects and miscarriage rate

PMA481

Youssef 2016b

Volume expanders for prevention of OHSS

9 RCTs

1660 (albumin) + 487 (HES) women

at high risk of developing OHSS undergoing ART cycles High risk: determined as number of follicles or oestradiol levels on day of hCG, as defined by included studies

Human albumin

Hydroxyethyl starch (HES)

Placebo/no treatment

OHSSa

Clinical pregnancy

Number of oocytes retrieved

Multiple pregnancy

Miscarriage

Live birth

No reporting of live birth rate

Limited by incomplete data reporting and lack of (details on) blinding

HA413

Youssef 2016

Recombinant vs urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles

18 RCTs

2952 women undergoing ART

Recombinant hCG

Recombinant LH

Urinary hCG

OHSSa

Clinical pregnancy

Miscarriage

Oocytes retrieved

Tolerance

Live birth

Review authors combined ongoing pregnancy and live births together

Only 7 trials reported on live birth

Trials lacked details on allocation concealment, randomisation and blinding

MM1690

Youssef 2014

GnRHa vs hCG for oocyte triggering in antagonist‐assisted reproductive technology

17 RCTs

1847 women undergoing ART

GnRH agonist

hCG

OHSSa

Live birth ratea

Ongoing pregnancy

Clinical pregnancy

Multiple pregnancy

Miscarriage rate

Risk of bias in included studies. Limitations included premature termination, failure to clearly report methods and substantial heterogeneity

Adverse events such as multiple pregnancy rate were not well reported

AWP1710

Pouwer 2015

Long‐acting FSH vs daily FSH for women undergoing assisted reproduction

6 RCTs

3753 women with subfertility

Long‐acting FSH

Daily FSH

OHSSa

Live birth ratea

Ongoing pregnancy rate

Clinical pregnancy rate

Multiple pregnancy rate

Miscarriage rate

Adverse events

Satisfaction

Limited by risk of attrition bias in some primary studies and by serious imprecision

LDT120

Tso 2014

Metformin treatment before and during IVF or ICSI in women with PCOS

9 RCTs

816 women with PCOS

Metformin

Placebo

No treatment

OHSSa

Live birtha

Clinical pregnancya Miscarriage

Adverse events Number of oocytes

retrieved

Total dose FSH (IU) Number of days

gonadotrophin treatment

Cycle cancellation rate

Serum E2 level (nmol/L)

Half the trials were not blinded and lacked details on allocation concealment and randomisation

AM1335

Gibreel 2012

Clomiphene citrate in combination with gonadotropins for controlled ovarian stimulation in women undergoing IVF

14 RCTs,

12 for meta‐analysis

2536 (12 trials)

Subfertile women undergoing ART

Clomiphene citrate

± additional treatments

Alternative treatments for

COH

OHSSa

Live birth ratea

Miscarriage rate

Ectopic pregnancy

Foetal abnormality

Ongoing pregnancy rate

Cancellation rate

Live birth reported in only 5 trials

Most studies suffered from suboptimal methods and information on some outcomes was insufficient

TA1860

Allersma 2013

Natural cycle IVF for subfertile couples

5 RCTs

382 subfertile women and couples undertaking IVF treatment

Natural cycle IVF

Modified natural cycle IVF

COH IVF

OHSSa

Live birtha

Pregnancy

Ongoing pregnancy

Number of oocytes retrieved

Time to live birth

Number of cycles required to conceive

Cumulative pregnancy/live birth rate

Multiple pregnancy

Lack of embryos for cryopreservation

Cycle cancellation

Gestational abnormalities

Cancellation of treatment

Cost‐effectiveness

Few studies, live birth reported in only 1 very small trial

Inclusion criteria differed

MV263

van der Linden 2015

Luteal phase support for ART cycles

94 RCTs

26,198 women with any cause of subfertility undergoing ART

Progesterone

hCG

Placebo or no treatment

hCG

Progesterone + oestrogen Progesterone + GnRHa

Live birtha

Clinical pregnancy

Ongoing pregnancy

Miscarriage

OHSS

Multiple pregnancy

Poor reporting of study methods and imprecision due to small sample sizes

HA412

Al‐Inany 2016

Gonadotrophin‐releasing hormone antagonists for ART

73 RCTs

12,212 women undergoing ART

GnRH antagonist

Long‐course GnRHa

OHSSa

Live birtha

Ongoing pregnancy

Clinical pregnancy

Miscarriage

Cycle cancellation

Only 12 trials reported live birth

Trial methods limited by lack of blinding

Poor reporting of study methods for OHSS

AMY731

Yossry 2006

IVF vs tubal re‐anastomosis (sterilisation reversal) for subfertility after tubal sterilisation

No RCTs

NA

IVF

Tubal re‐anastomosis

Live birtha

Clinical pregnancy Multiple pregnancy

Other serious maternal morbidity, (incl OHSS)

Empty review with no

trials

No longer being updated

ZP672

Pandian 2015

IVF for unexplained subfertility

6 RCTs

733 couples with unexplained subfertility

IVF

Expectant management

Intrauterine insemination Intrauterine insemination +

ovarian stimulation

Clomiphene citrate

Live birtha

OHSS

Clinical pregnancy Multiple pregnancy

Some evidence was based

on a single trial

Limitations included imprecision and heterogeneity for some outcomes

LA541

Albuquerque 2013

Depot vs daily administration of GnRHa protocols for pituitary desensitisation in assisted reproduction cycles

16 RCTs,

12 for meta‐analysis

1811 couples with any cause of subfertility undergoing IVF with COH with hFSH, hMG or rFSH

Pituitary downregulation with depot administration of GnRHa

Daily administration of GnRHa

OHSSa

Live birtha

Clinical pregnancya

Miscarriage

Multiple pregnancy

S tudy quality unclear due to poor reporting. O nly four stu dies reported live birth an d only five described adequate methods for allocation concealment .

IOK973

van Wely 2011

Recombinant vs urinary gonadotrophin for ovarian stimulation in ART cycles

42 RCTs

9606 normogonadotrophic women undergoing fresh and/or frozen thawed IVF or ICSI cycles

Recombinant FSH

Urinary FSH

OHSSa

Live birtha

Clinical pregnancy

Miscarriage

Multiple pregnancy

Adverse effects

No difference reported in moderate/severe OHSS

WPM1780

Martins 2013

FSH replaced by low‐dose hCG in the late follicular phase vs continued FSH for ART

5 RCTs

351 women undergoing COH for ART

Low‐dose hCG instead of FSH in late follicular phase

Continued FSH in late follicular phase

OHSSa

Live birtha

Clinical pregnancy

Miscarriage

Small studies and low event rate

Total OHSS incidence reported

DHH752

Smulders 2010

Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing ART

23 RCTs

2596 women of any age with subfertility regardless of cause, undergoing ART

Pretreatment with combined oral contraceptive pills

Pretreatment with progestogens

No pretreatment

Placebo

Progestogens

Oestrogens

Live birtha

OHSS

Clinical pregnancy

Miscarriage

Multiple pregnancy

Adverse effects

Only 3/23 studies reported on OHSS

2 of these 3 studies did not define how they diagnosed the condition

IOK972

Kwan 2014

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)

6 RCTs

781 women undergoing COH in an IVF/ICSI cycle

Transvaginal ultrasonography + Oestradiol measurement

Transvaginal ultrasonography

Live birtha

OHSS

Clinical pregnancy

Miscarriage

Multiple pregnancy

Adverse effects

Only total OHSS reported, including mild OHSS

CMB1261

Boomsma 2012

Peri‐implantation glucocorticoid administration for ART cycles

14 RCTs

1879 subfertile patients undergoing IVF/ICSI, regardless of cause of infertility

Glucocorticoids in the peri‐implantation phase

No glucocorticoids in the peri‐implantation phase

Live birtha

Multiple pregnancya

OHSS

Clinical pregnancy Miscarriage

Adverse effects

Only 2 studies, pooled total OHSS

VJP951

Siristatidis 2016

Aspirin for IVF

13 RCTs

2653 women undergoing IVF/ICSI and their partners

Aspirin

No treatment

Placebo

Live birtha

OHSS

Clinical pregnancy Miscarriage

Multiple pregnancy

Adverse effects

Only 1 of 13 studies reported on OHSS and without exact numbers or explanation for numerators/denominators

CS1400

Siristatidis 2009

In vitro maturation in subfertile women with PCOS undergoing assisted reproduction

None

0 women with PCOS and subfertility

In vitro maturation + IVF/ICSI in women with PCOS

Conventional IVF/ICSI in women with PCOS

Live birtha

OHSS

Effectiveness

Clinical pregnancy Miscarriage

Adverse effects

Empty review

IRS911

Cheong 2013

Acupuncture and ART

20 RCTs

4544 women undergoing ART, any type of acupuncture at any time point before, after or during ART, intended to improve ART outcome

Acupuncture of men, women or both during COH

Acupuncture + ART

Acupuncture alone

No treatment

Placebo

Sham acupuncture

Acupuncture + ART

Live birtha

OHSS

Clinical pregnancy Miscarriage

Multiple pregnancy

Adverse effects

No trials reported on OHSS

MHM931

Mochtar 2007

Recombinant luteinising hormone (rLH) for COH in assisted reproductive cycles

14 RCTs

2612 subfertile ovulatory women undergoing IVF or ICSI

High risk: NA

Combination of rLH and rFSH for COH in IVF/ICSI followed by ET in GnRHa and GnRH antagonist protocols

rFSH alone for COH in IVF/ICSI followed by ET in GnRHa and GnRH antagonist protocols

OHSSa

Live birtha

Clinical pregnancy Miscarriage

Only 4/14 trials reported on OHSS

Pooled OHSS

No GRADE assessment in old version

KH291

Duffy 2010

Growth hormone for IVF

10 RCTs

440 women part of a subfertile couple undergoing IVF

Adjuvant growth hormone during conventional IVF

Conventional IVF

Live birtha

OHSS

Clinical pregnancy

Adverse effects

Only 4 of 10 RCTs reported on adverse events (which could include OHSS)

1 study actually mentioned OHSS (however, no cases); pooled OHSS

SD265

Siristatidis 2015

GnRHa protocols for pituitary suppression in assisted reproduction

37 RCTs

3872 women/couples with all types of infertility undergoing ART and using GnRHa for pituitary downregulation

Long protocol

Long luteal protocol

Short protocol

Dose continued

Dose continued after hCG administration

Pretreatment 2 weeks

Short protocol

Ultrashort protocol

Long follicular phase protocol

Ultrashort protocol

Dose stopped

Dose reduced

Dose discontinued after hCG administration

Pretreatment 3 weeks

Live birtha

OHSS

Clinical pregnancy Adverse effects

Only 2 of 37 included RCTs reported on OHSS for 2 of 9 compared regimens

JC1630

Showell 2013

Antioxidants for female subfertility

28 RCTs

3548 subfertile women referred to fertility clinic who might or might not undergo ART (IVF, ICSI or IUI)

Adjuvant antioxidants in females

No treatment

Placebo

Another antioxidant

Live birtha

Clinical pregnancy Miscarriage

Multiple pregnancy

Adverse effects (incl OHSS)

Only 3 studies reported: 1 no data and 2 no cases

aPrimary review outcome.

ART: artifical reproductive technology.

COH: controlled ovarian hyperstimulation.

ET: embryo transfer.

FSH: follicle‐stimulating hormone.

GnRHa: gonadotrophin‐releasing hormone agonist.

hCG: human chorionic gonadotrophin.

HES: hydroxyethyl starch.

hFSH: human follicle‐stimulating hormone.

hMG: human menopausal gonadotrophin.

ICSI: intracytoplasmic sperm injection.

IUI: intrauterine insemination.

IVF: in vitro fertilisation.

LH: luteinising hormone.

NA: not applicable.

OHSS: ovarian hyperstimulation syndrome.

PCOS: polycystic ovary syndrome.

RCT: randomised controlled trial.

rFSH: recombinant follicle‐stimulating hormone.

rLH: recombinant luteinising hormone.

Figuras y tablas -
Table 1. Review characteristics
Table 2. Last search date assessment

Review no.

First review author

Review title

Date last assessed
up to date

< 3 years since last assessed up to date or deemed stable

ADA561

D'Angelo 2007

Embryo freezing for preventing OHSS

26/11/2010

Stable

ADA 563

D'Angelo 2011

Coasting (withholding of gonadotrophins) for preventing OHSS

19/07/2010

X

TH1338

Tang 2016

Dopamine agonists for preventing OHSS

15/08/2016

PMA481

Youssef 2016b

Volume expanders for prevention of OHSS

21/09/2016

HA413

Youssef 2016

Recombinant vs urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles

23/04/2015

MM1690

Youssef 2014

GnRHa vs hCG for oocyte triggering in antagonist‐assisted reproductive technology

08/09/2014

X

LDT1201

Tso 2014

Metformin treatment before and during IVF or ICSI in women with PCOS

15/10/2014

AWP1710

Pouwer 2015

Long‐acting FSH vs daily FSH for women undergoing assisted reproduction

8/06/2015

AM1335

Gibreel 2012

Clomiphene citrate in combination with gonadotrophins for controlled ovarian stimulation in women undergoing IVF

23/03/2012

X

TA1860

Allersma 2013

Natural cycle IVF for subfertile couples

5/03/2013

MV263

van der Linden2015

Luteal phase support for ART cycles

25/11/2014

HA412

Al‐Inany 2016

Gonadotrophin‐releasing hormone antagonists for ART

28/04/2016

AMY731

Yossry 2006

IVF vs tubal re‐anastomosis (sterilisation reversal) for subfertility after tubal sterilisation

15/05/2009

Empty, stable

ZP672

Pandian 2015

IVF for unexplained subfertility

4/05/2015

LA541

Albuquerque 2013

Depot vs daily administration of GnRHa protocols for pituitary desensitisation in assisted reproduction
cycles

3/07/2012

IOK973

van Wely 2011

Recombinant vs urinary gonadotrophin for ovarian stimulation in ART cycles

20/10/2010

X

WPM1780

Martins 2013

FSH replaced by low‐dose hCG in late follicular phase vs continued FSH for ART

5/02/2013

DHH752

Smulders 2010

Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing ART

16/11/2008

X

IOK972

Kwan 2014

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)

30/05/2014

CMB1261

Boomsma 2012

Peri‐implantation glucocorticoid administration for ART cycles

20/09/2011

X

VJP951

Siristatidis 2016

Aspirin for IVF

9/05/2016

CS1400

Siristatidis 2009

In vitro maturation in subfertile women with PCOS undergoing assisted reproduction

17/02/2011

Empty

IRS911

Cheong 2013

Acupuncture and ART

22/07/2013

MHM931

Mochtar 2007

Recombinant luteinising hormone (rLH) for COH in assisted reproductive cycles

25/01/2007

X

KH291

Duffy 2010

Growth hormone for IVF

20/07/2009

X

SD265

Siristatidis 2015

GnRHa protocols for pituitary suppression in assisted reproduction

23/04/2015

JC1630

Showell 2013

Antioxidants for female subfertility

15/04/2014

ART: artifical reproductive technology.

COH: controlled ovarian hyperstimulation.

FSH: follicle‐stimulating hormone.

GnRHa: gonadotrophin‐releasing hormone agonist.

hCG: human chorionic gonadotrophin.

ICSI: intracytoplasmic sperm injection.

IUI: intrauterine insemination.

IVF: in vitro fertilisation.

OHSS: ovarian hyperstimulation syndrome.

PCOS: polycystic ovary syndrome.

rLH: recombinant luteinising hormone.

✔ under 3 years since last assessed as up to date

X over 3 years since last assessed as up to date

Figuras y tablas -
Table 2. Last search date assessment
Table 3. AMSTAR assessment per review

Review no.

First review author + year

Review title

AMSTAR criteria

Prespecified question and inclusion criteria

Duplicate study selection and data extraction

Comprehensive literature search

Grey literature included

Lists included and excluded studies

Describes characteristics of included studies

Study quality assessed

Studies combined using appropriate methods

Likelihood of publication bias considered/tested

Potential for conflict of interest addressed

ADA561

D'Angelo 2007

Embryo freezing for preventing ovarian hyperstimulation syndrome

ADA 563

D'Angelo 2011

Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome

TH1338

Tang 2016

Dopamine agonists for preventing ovarian hyperstimulation syndrome

PMA481

Youssef 2016b

Volume expanders for the prevention of ovarian hyperstimulation syndrome

HA413

Youssef 2016

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

MM1690

Youssef 2014

Gonadotropin‐releasing hormone agonist versus hCG for oocyte triggering in antagonist‐assisted reproductive technology

LDT1201

Tso 2014

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome

AWP1710

Pouwer 2015

Long‐acting FSH versus daily FSH for women undergoing assisted reproduction

AM1335

Gibreel 2012

Clomiphene citrate in combination with gonadotrophins for controlled ovarian stimulation in women undergoing in vitro fertilisation

TA1860

Allersma 2013

Natural cycle IVF for subfertile couples

MV263

van der Linden 2015

Luteal phase support for ART cycles

HA412

Al‐Inany 2016

Gonadotrophin‐releasing hormone antagonists for assisted reproductive technology

AMY731

Yossry 2006

In vitro fertilisation versus tubal re‐anastomosis (sterilisation reversal) for subfertility after tubal sterilisation

NA

NA

NA

NA

ZP672

Pandian 2015

In vitro fertilisation for unexplained subfertility

LA541

Albuquerque 2013

Depot versus daily administration of gonadotrophin‐releasing hormone
agonist protocols for pituitary desensitisation in assisted reproduction
cycles

IOK973

van Wely 2011

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

WPM1780

Martins 2013

FSH replaced by low‐dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques

DHH752

Smulders 2010

Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques

IOK972

Kwan 2014

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)

CMB1261

Boomsma 2012

Peri‐implantation glucocorticoid administration for assisted reproductive technology cycles

VJP951

Siristatidis 2016

Aspirin for in vitro fertilisation

CS1400

Siristatidis 2009

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction

NA

NA

NA

NA

IRS911

Cheong 2013

Acupuncture and assisted reproductive technology

MHM931

Mochtar 2007

Recombinant luteinising hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles

X

KH291

Duffy 2010

Growth hormone for in vitro fertilisation

X

SD265

Siristatidis 2015

Gonadotrophin‐releasing hormone agonist protocols for pituitary suppression in assisted reproduction

JC1630

Showell 2013

Antioxidants for female subfertility

Search date: 24/07/2016.

ART: artifical reproductive technology.

FSH: follicle‐stimulating hormone.

hCG: human chorionic gonadotrophin.

ICSI: intracytoplasmic sperm injection.

IUI: intrauterine insemination.

IVF: in vitro fertilisation.

NA: not applicable.

rLH: recombinant luteinising hormone.

Figuras y tablas -
Table 3. AMSTAR assessment per review
Table 4. Summary of findings for OHSS: per review and/or per intervention

Review title and

comparison intervention/control

Assumed risk with comparator

Corresponding risk

with intervention

Relative effect

(95% CI)

Number of participants

(studies)

Quality of the evidence

(GRADE)

Comments

D'Angelo 2007

Embryo freezing for preventing ovarian hyperstimulation syndrome

(Embryo freezing vs fresh transfer)

Overall OHSS: 60 per 1000

Overall OHSS: 125 per 1000

(62 to 240)

OR 1.12

(0.01 to 2.29)

125

(1 study)

Low

Imprecision, number of events < 300

Evidence based on a single open‐label study with insufficient methodological details provided

D'Angelo 2007

Embryo freezing for preventing ovarian hyperstimulation syndrome

(Embryo freezing vs intravenous albumin)

Moderate or

severe OHSS:

77 per 1000

Moderate or

severe OHSS:

308 per 1000

(41 to 824)

OR 5.33

(0.51 to 56.24)

26

(1 study)

Very low

Imprecision, number of events < 300

Evidence based on a single open‐label trial

D'Angelo 2011

Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome

Moderate or

severe OHSS:

265 per 1000

Moderate or

severe OHSS:

58 per 1000

(11 to 241)

OR 0.17

(0.03 to 0.88)

68

(1 study)

Very low

Imprecision, number of events < 300

Evidence based on a single conference abstract
Insufficient methodological details provided

Tang 2016

Dopamine agonists for preventing ovarian hyperstimulation syndrome

Moderate or severe OHSS: 286 per 1000

Moderate or severe OHSS: 97 per 1000

(71 to 135)

OR 0.27

(0.19 to 0.39)

2091

(16 studies))

Moderate

Imprecision, number of events < 300

Lack of details for allocation concealment and blinding, selective reporting

Youssef 2016b

Volume expanders for the prevention of ovarian hyperstimulation syndrome

(human albumin vs placebo/no treatment)

Moderate or severe OHSS:

122 per 1000

Moderate or severe OHSS: 85 per 1000 (61 to 177)

OR 0,67

(0.47 to 0.95)

1452

(7 studies)

Very low

Imprecision, number of events < 300

Lack of details on allocation concealment and selective reporting

Youssef 2016b

Volume expanders for the prevention of ovarian hyperstimulation syndrome

(HES vs placebo)

Moderate or

severe OHSS: 164 per 1000

Moderate or

severe OHSS: 50 per 1000

(23 to 104)

OR 0.27

(0.12 to 0.59

272

(2 studies)

Very low

Imprecision, number of events < 300

Lack of details on allocation concealment and selective reporting

Youssef 2016b

Volume expanders for the prevention of ovarian hyperstimulation syndrome

(mannitol vs placebo)

Moderate or

severe OHSS: 517 per 1000

Moderate or

severe OHSS: 289 per 1000

(191 to 407)

OR 0.38

(0.22 to 0.64)

226

(1 study)

Low

Imprecision, number of events < 300

Lack of details on allocation concealment and selective reporting

Youssef 2016

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles (r‐hCG vs u‐hCG)

Overall OHSS: 27 per 1000

Overall OHSS:40 per 1000

(15 to 102)

OR 0.39

(0.25 to 0.61)

374

(3 studies)

Moderate

Imprecision, number of events < 300

One of the trials lacked methodological details on randomisation, allocation concealment and blinding

Youssef 2016

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles (r‐LH vs u‐hCG)

Overall OHSS: 10 per 1000

Overall OHSS:

17 per 1000

(11 to 84)

OR 1.76

(0.37 to 8.45)

417

(3 studies)

Low

Imprecision, number of events < 300

One of the trials lacked adequate methodological details

Youssef 2014

Gonadotropin‐releasing hormone agonist versus hCG for oocyte triggering in antagonist‐assisted reproductive technology

Overall OHSS: 5 per 1000

Overall OHSS:

1 per 1000

(0 to 2)

OR 0.15

(0.05 to 0.47)

989

(9 studies)

Moderate

Imprecision, number of events < 300

All studies at high risk of bias in 1 or more domains

None clearly reported blinded outcome assessment

Tso 2014

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome.

Overall OHSS: 270 per 1000

Overall OHSS: 97 per 1000

(62 to 153)

OR 0.29

(0.18 to 0.49)

798

(8 studies)

Moderate

Imprecision, number of events < 300

Pouwer 2015

Long‐acting FSH versus daily FSH for women undergoing assisted reproduction

(low dose)

Overall OHSS: 47 per 1000

Overall OHSS: 57 per 1000

(26 to 125)

RR 1.22

(0.56 to 2.66)

645

(3 studies)

Moderate

Imprecision, number of events < 300

Pouwer 2015

Long‐acting FSH versus daily FSH for women undergoing assisted reproduction

(medium dose)

Overall OHSS: 63 per 1000

Overall OHSS: 60 per 1000 (45 to 85)

RR 0.96

(0.68 to 1.35)

3075

(5 studies)

Low

Imprecision, number of events < 300

Confidence intervals compatible with clinically meaningful benefit in either arm or with no effect, plus high risk of attrition bias in 2 studies

Pouwer 2015

Long‐acting FSH versus daily FSH for women undergoing assisted reproduction

(high dose)

Overall OHSS: 0 per 1000

Overall OHSS: 0 per 1000

(0 to 0)

RR 1.73

(0.09 to 32.75)

33

(1 study)

Very low

Imprecision, number of events < 300

High risk of attrition bias

Gibreel 2012

Clomiphene citrate in combination with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation

(clomiphene + gonadotropins vs gonadotropins)

Overall OHSS: 50 per 1000

Overall OHSS:12 per 1000

(5 to 27)

OR 0.23

(0.1 to 0.52)

1559

(5 studies)

Low

Imprecision, number of events < 300

Very wide 95% confidence interval crossing the threshold points of appreciable benefit or harm, which is 25%

Allersma 2013

Natural cycle IVF for subfertile couples

(natural cycle vs conventional IVF)

Overall OHSS: 67 per 1000

Overall OHSS:

13 per 1000

(1 to 393)

OR 0.10

(0.01 to 4.06)

60

(1 study)

Very low

Imprecision, number of events < 300

Only 1 study reporting on OHSS

Allocation concealment method not reported

van der Linden 2015

Luteal phase support for ART cycles

(hCG versus placebo/no treatment)

Overall OHSS: 41 per 1000

Overall OHSS:

155 per 100

(76 to 292)

OR 4.28

(1.191 to 9.6)

387

(1 study)

Low

Imprecision, number of events < 300

Poor reporting of study methods

van der Linden 2015

Luteal phase support for ART cycles

(progesterone vs hCG regimens)

Overall OHSS: 126 per 1000

Overall OHSS: 72 per 1000

(31 to 162)

OR 0.54

(0.22 to 1.34)

615

(4 studies)

Low

Imprecision, number of events < 300

Poor reporting of study methods

van der Linden 2015

Luteal phase support for ART cycles

(progesterone + GnRH agonist)

Overall OHSS: 50 per 1000

Overall OHSS: 50 per 1000

(17 to 137)

OR 1.00

(0.33 to 3.01)

300

(1 study)

Very low

Imprecision, number of events < 300

Poor reporting of study methods

van der Linden 2015

Luteal phase support for ART cycles

(progesterone vs progesterone + oestrogens)

Overall OHSS: 39 per 1000

Overall OHSS: 22 per 1000

(8 to 62)

OR 0.56

(0.2 to 1.63)

461

(2 studies)

Low

Imprecision, number of events < 300

Poor reporting of study methods

Al‐Inany 2016

Gonadotrophin‐releasing hormone antagonists for assisted reproductive technology

(GnRH antagonist vs GnRH agonist)

Overall OHSS: 114 per 1000

Overall OHSS: 73 per 1000

(62 to 85)

OR 0.61
(0.51 to 0.72)

7944

(36 studies)

Moderate

Methodological limitations including poor allocation concealment and lack of blinding

Yossry 2006

In vitro fertilisation versus tubal reanastomosis (sterilisation reversal) for subfertility after tubal sterilisation

(IVF vs tubal reanastomosis)

NA

NA

NA

NA

NA

Empty review

Pandian 2015

In vitro fertilisation for unexplained subfertility

(IVF vs IUI + gonadotropins/clomiphene citrate)

Overall OHSS: 58 per 1000

Overall OHSS: 66 per 1000

(26 to 158)

OR 1.15 (0.43 to 3.06)

324

(2 studies)

Low

Imprecision, number of events < 300

Only 2 studies on OHSS reported

Albuquerque 2013

Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles

(depot vs daily gonadotropins)

Overall OHSS: 3 per 100

Overall OHSS: 2 per 100
(1 to 6)

OR 0.84
(0.29 to 2.42)

570

(5 studies)

Low

Most studies were classified as at unclear risk of bias for all domains

Imprecision, number of events < 300
Studies were insufficient to assess publication bias

van Wely 2011

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

(rFSH vs HMG/HMG‐HP)

Overall OHSS: 17 per 1000

Overall OHSS: 17 per 1000

(10 to 28)

OR 1.00

(0.58 to 1.71)

3197

(11 studies)

High

Imprecision, number of events < 300

van Wely 2011

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

(rFSH vs FSH‐P)

Overall OHSS: 28 per 1000

Overall OHSS:49 per 1000

(25 to 95)

OR 1.79

(0.89 to 3.62)

1490

(6 studies)

Higha

Imprecision, number of events < 300

van Wely 2011

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

(rFSH vs FSH‐HP)

Overall OHSS: 28 per 1000

Overall OHSS:

31 per 1000

(20 to 48)

OR 1.11

(0.70 vs 1.75)

3053

(14 studies)

Higha

Two additional trials excluded in sensitivity analyses because it was unclear if data were reported according to ITT analysis (those were included for "Overall OHSS")

van Wely 2011

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

(rec‐hCG vs u‐hCG)

Overall OHSS: 19 per 1000

Overall OHSS:

22 per 1000

(16 to 30)

OR 1.18 (0.86 vs 1.61)

7740

(32 studies)

Higha

Imprecision number of events < 300

Martins 2013

FSH replaced by low‐dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques

(low‐dose hCG vs FSH in late follicular phase)

Overall OHSS: 3 per 100

Overall OHSS: 1 per 100

(0 to 4)

OR 0.30 (0.06 to 1.59)

351

(5 studies)

Very low

Imprecision, number of events < 300

Inconsistency, high risk of bias

Smulders 2010

Oral contraceptive pill, progestogen or oestrogen pre‐ treatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques

(OAC plus antagonist vs antagonist)

Overall OHSS: 17 per 1000

Overall OHSS: 25 per 1000

(5 to 133)

OR 1.5 (0.26 to 8.8)

234

(1 study)

Very low

Single study reporting on OHSS

Imprecision, number of events < 300

Wide confidence intervals that cross line of no effect

High risk of attrition bias

Smulders 2010

Oral contraceptive pill, progestogen or oestrogen pre‐ treatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques

(OAC plus antagonist vs agonist)

Overall OHSS: 55 per 1000

Overall OHSS: 35 per 1000

(12 to 100)

OR 0.63

(0.21 to 1.92)

290 (2 studies)

Very low

Imprecision, number of events < 300

One study at high risk of attrition bias

Kwan 2014

Monitoring of stimulated cycles in assisted reproduction

(IVF and ICSI)

(transvaginal ultrasound + estradiol vs transvaginal ultrasound)

Overall OHSS: 36 per 1000

Overall OHSS: 36 per 1000

(18 to 75)

OR 1.03

(0.48 to 2.20)

781

(6 studies)

Low

Imprecision, number of events < 300 with wide confidence intervals

Methods of randomisation inadequately described in 3 of 6 trials, allocation concealment inadequately described in all 6 trials and blinding inadequately described in 5 of 6 trials

No definition of OHSS provided by authors of these 6 studies

Boomsma 2012

Peri‐implantation glucocorticoid administration for assisted reproductive technology cycles

(adjuvant glucocorticoids vs no glucocorticoids)

Overall OHSS: 194 per 1000

Overall OHSS: 159 per 1000

(64 to 392)

OR 0.82 (0.33 to 2.02)

151

(2 studies)

Low

Imprecision, number of events < 300

Siristatidis 2016

Aspirin for in vitro fertilisation

(aspirin vs no treatment/placebo)

NA

NA

NA

NA

NA

Only 1 study reported on OHSS; no exact numbers or explanation of numerators/denominators given

Siristatidis 2009

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction

(IVM vs conventional IVF)

NA

NA

NA

NA

NA

Empty review

Cheong 2013

Acupuncture and assisted reproductive technology

(acupuncture vs no acupuncture/sham acupuncture)

NA

NA

NA

NA

NA

No studies reported on OHSS

Mochtar 2007

Recombinant luteinizing hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles

(combined rLH + FSH vs FSH )

Overall OHSS: 20 per 1000

Overall OHSS:

27 per 1000

(12 to 59)

OR 1.34

(0.58 to 3.09)

986

(7 studies)

Low

Imprecision, number of events < 300

Some methodological details unclear

Duffy 2010

Growth hormone for in vitro fertilization

(growth hormone vs no treatment/placebo)

NA

NA

NA

NA

NA

Only 1 study reported on OHSS; however, no cases of OHSS were reported

Siristatidis 2015

Gonadotropin‐releasing hormone agonist protocols for pituitary suppression in assisted reproduction

(different protocols vs other protocol)

Overall OHSS: 20 per 1000

Overall OHSS: 27 per 1000

(12 to 59)

OR 1.34

(0.58 to 3.09)

986

(7 studies)

Low

Imprecision, number of events < 300

Some methodological details unclear

Showell 2013

Antioxidants for female subfertility

(antioxidants vs no treatment/placebo/other antioxidant)

NA

NA

NA

NA

NA

Although 3 studies reported on OHSS, no numbers were given, so effect size could not be calculated

aReview authors GRADED these outcomes as 'high quality'; however, the total event rate < 300 would justify downgrading for this to moderate‐quality evidence.

ART: artifical reproductive technology.

FSH: follicle‐stimulating hormone.

FSH‐HP: highly purified FSH.

hCG: human chorionic gonadotrophin.

HES: hydroxyethyl starch.

ICSI: intracytoplasmic sperm injection.

IUI: intrauterine insemination.

IVF: in vitro fertilisation.

IVM: in vitro maturation.

NA: not applicable.

OAC: oral anticoagulant.

OHSS: ovarian hyperstimulation syndrome.

OR: odds ratio.

rFSH: recombinant follicle‐stimulating hormone.

r‐hCG: recombinant human chorionic gonadotrophin.

rLH: recombinant luteinising hormone.

Total: any grade of OHSS.

u‐hCG: urinary human chorionic gonadotrophin.

Figuras y tablas -
Table 4. Summary of findings for OHSS: per review and/or per intervention