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Table 1 Methodological characteristics of eligible studies

From: The role of endometrial scratching prior to in vitro fertilization: an updated systematic review and meta-analysis

Study, country of origin, number of centers, journal or meeting

Study period

Number of patients randomized

Randomization method

Allocation concealment

Blinding

Prospective power analysis performed

Primary outcome assessed

Financial Support

Protocol Registration

Authors contacted

Karim Zadeh et al., (2008) [11], Iran, single center, Human Reproduction

Not reported

160 (endometrial scratching: 80, control: 80)

Not reported

Not reported

Not reported

Not reported

Implantation (definition not reported)

Not reported

Not reported

Attempted; No response

Karimzadeh et al., (2009) [12], Iran, single center, Australian and New Zealand Journal of Obstetrics and Gynaecology

Not reported

115 (endometrial scratching: 58, control: 57)

Manual randomization (drawing a piece of paper from a bag)

Not reported

Not reported

Yes

Pregnancy (definition not reported)

Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences

Not reported

Attempted; No response.

Karimzade et al., (2010) [13], Iran, single center, Archives of Obstetrics and Gynaecology

1 June,2008- 1 January, 2009

156 (endometrial scratching: 77, control: 79)

Computer generated randomization method

Not reported

Not reported

Not reported

Implantation (gestational sacs on U/S)

Not reported

Yes (retrospectively)

Attempted; No response

Narvekar et al., (2010) [14], India, single center, Journal of Human Reproductive Sciences

May 2007- July 2008

100 (endometrial scratching: 49, control: 51)

Computer-generated random numbers

Third- party sealed consecutively numbered opaque envelopes

Non-blind

Not reported

Live birth (definition not reported)

Not reported

Not reported

Attempted; No response

Safdarian et al., (2011) [15], Iran, single center, Iranian Journal of Reproductive Medicine

July 2008- March 2009

100 (endometrial scratching: 50, control: 50)

Computerized randomization

Not reported

Not reported

Not reported

Implantation (definition not reported)

Infertility Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Yes (retrospectively)

Attempted; No response

Baum et al., (2012) [16], Israel, single center, Gynecological Endocrinology

July 2006- June 2009

36 (endometrial scratching: 18, control: 18)

Table of random numbers

Not reported

Single-blind (patients did not know in which group they were)

Not reported

Implantation (definition not reported)

Clinical pregnancy (intrauterine gestational sac with embryonic pole on U/S)

Not reported

Not reported

Attempted; No response

Inal et al., (2012) [17], Turkey, single center, European Journal of General Medicine

January 2008- March 2009

100 (endometrial scratching: 50, control: 50)

Computer-generated random numbers

Not reported

Not reported

Not reported

Live birth (Definition not reported)

None

Not reported

Attempted; No response

Shohayeb et al., (2012) [18], Egypt and Saudi Arabia, double center, European Journal of Obstetrics & Gynecology and Reproductive Biology

Not reported

210 (endometrial scratching: 105, control: 105)

Random number tables

Third- party closed sealed envelopes

Not reported

Not reported

Implantation (attachment of the embryo to the endometrium during a specific period which is called the window of implantation) Clinical pregnancy (gestational sac with embryonic cardiac activity) Abortion (definition not reported)

Live birth (definition not reported)

Not reported

Not reported

Attempted; No response

Nastri et al., (2013) [19], Brazil, single center, Ultrasound Obstetrics Gynecology

June 2010- March 2012

158 (endometrial scratching: 79, control: 79)

Computer generated random sequence of numbers in blocks of 30 (each block having 15 numbers assigned to intervention and 15 to control)

Third- party sealed consecutively numbered opaque envelopes

Assigned as the participant entered the study; opened just before the procedure

Double-blind

Yes

Clinical pregnancy (at least one fetus with cardiac activity per allocated woman)

Brazilian official government research foundations: CNPq and CAPES

Yes

Attempted; No response

Guven et al., (2014) [20], Turkey, single center, European Journal of obstetrics and gynecology and reproductive biology

September 2010- April 2011

124 (endometrial scratching: 62, control: 62)

Not reported

Sealed envelopes

Not reported

Not reported

Clinical pregnancy (intrauterine gestational sac with embryonic cardiac activity on TVS, 4 weeks after ET)

Not reported

Not reported

Attempted; No response

Yeung et al., (2014) [21], Hong Kong, single center, Human Reproduction

March 2011- August 2013

300 (endometrial scratching: 150, control: 150)

Randomization in a 1: 1 ratio according to a computer-generated randomization list with blocks of 10 in sealed envelopes

Third- party sealed envelopes

Non-blind

Yes

Ongoing pregnancy (at least one sac with embryonic cardiac activity on U/S beyond 20 weeks of gestation)

Small Project Funding of the Committee on Research and Conference Grants, University of Hong Kong

Yes

No

Gibreel et al., (2015) [22], Egypt, multicenter, Gynecology Endocrinology

Not reported

387 (endometrial scratching: 193, control: 194)

Computer-generated tables of random numbers

Opaque sealed envelopes (on the day of start of pituitary downregulation)

Single-blind (patients did not know in which group they were)

Yes

Live birth (delivery of one or more living fetuses after 24 weeks of gestation)

Not reported

Yes

Attempted; No response.

Singh et al., (2015) [23], India single center, Journal of Human Reproductive Sciences

April 2013- July 2014

60 (endometrial scratching: 30, control: 30)

Random allocation software

Not reported

Non-blind

Not reported

Implantation (gestational sac on TVS)

None

Not reported

Attempted; No response

Xu et al., (2015) [24], China, single center, Reproductive BioMedicine Online

July 2012- July 2013

79 (endometrial scratching+G-CSF: 13, G-CSF: 14, control: 52)

Randomized number table

Not reported

Not reported

Not reported

Endometrial thickness Clinical pregnancy (gestational sac containing yolk sac at TVS, including ectopic pregnancy) Live birth (definition not reported) Implantation (gestational sac on TVS 4 weeks after ET)

Not reported

Not reported

Attempted; No response

Zhang et al., (2015) [25], China, double center, Chinese Journal of Integrative Medicine

August 2009- March 2012

168 (endometrial scratching: 55, Chinese medicine: 56, control: 57)

Randomization with computer-generated list (concealed to the physician but not to the study nurse)

Not reported

Not reported

Not reported

Biochemical pregnancy (positive serum β-hCG level on day 14 after FET)

Clinical pregnancy (intrauterine gestational sac with a cardiac activity 3 weeks after a positive β-hCG test)

Shanghai Municipal Health Bureau Foundation of Chinese Traditional Medicine

Not reported

Attempted; No response

Aflatoonian et al., (2016) [26], Iran, single center, International Journal of Reproductive Biomedicine

March 2015- January 2016

100 (endometrial scratching: 50, control: 50)

Computer-generated randomization table

Not reported

Non-blind

Yes

Implantation (gestational sacs on TVS) Clinical pregnancy (gestational sac and embryonic cardiac activity on TVS 5 weeks after ET)

Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Yes (retrospectively)

Attempted; No response

Shahrokh-Tehraninejad et al., (2016) [27], Iran, single center, Journal of Family and Reproductive Health

January 2013- December 2014

120 (endometrial scratching: 60, control: 60)

Manual randomization (drawing a piece of printed paper from a plastic bag)

Not reported

Not reported

Not reported

Clinical pregnancy (intrauterine gestational sac on TVS during week 5 after FET)

Not reported

Yes (retrospectively)

Attempted; No response

Zygula et al., (2016) [28], Poland, European Journal of Obstetrics & Gynecology and Reproductive Biology

Not reported

120 (endometrial scratching: 59, control: 61)

Not reported

Not reported

Not reported

Not reported

Clinical pregnancy (definition not reported)

Not reported

Not reported

Attempted; No response

Liu et al., (2017) [29], China, single center, Reproductive Biology Endocrinology

February 2012- November 2014

142 (endometrial injury in proliferative phase: 38, endometrial injury in luteal phase: 32, control in proliferative phase: 36, control in luteal phase: 36)

Table of random numbers

Not reported

Single-blind (patients did not know in which group they were)

Not reported

Implantation (intrauterine gestational sac on U/S)

National Natural Science Foundation of China, Beijing Natural Science Foundation Project and Project Training High-Level Medical Technical Personnel in the Health System in Beijing

Yes (retrospectively)

Attempted; No response

Mak et al., (2017) [30], Hong Kong, single center, Reproductive Biomedicine Online

March 2013- April 2016

229 (endometrial scratching: 115, control: 114)

Computer-generated random numbers

Third party opaque sealed envelopes

Double-blind

Yes

Pregnancy (Positive urine pregnancy test)

Not reported

Yes

No

Tk et al., (2017) [31], India, single center, European Journal of Obstetrics, Gynecology and Reproductive Biology

April 2008- April 2015

111 (endometrial scratching: 55, control: 56)

Computer generated sequence generated in blocks of 10

Consecutively numbered sealed opaque envelopes

Non-blind

Yes

Clinical pregnancy (gestational sac on U/S)

None

Yes (retrospectively)

Attempted; No response

Maged et al., (2018) [32], Egypt, single center, International Journal of Gynecology and Obstetrics

January 1, 2016- March 31, 2017

300 (endometrial scratching: 150, control: 150)

Automated web-based randomization system

Sealed envelopes

Non-blind

Yes

Clinical pregnancy (embryonic cardiac activity within a gestational sac on U/S 4 weeks after ET) Implantation (gestational sacs on U/S 14 days after ET)

Not reported

Not reported

Yes

Pecorino et al., (2018) [33], Italy, single center, Italian Journal of Gynaecology and Obstetrics

Not reported

80 (endometrial scratching: 40, control: 40)

Not reported

Not reported

Non-blind

Not reported

Clinical pregnancy (intrauterine sac with embryonic cardiac activity on U/S) Implantation (definition not reported)

Not reported

Not reported

Attempted; No response

Sherif et al., (2018) [34], Egypt, single center, Middle East Fertility Society Journal

Not reported

60 (endometrial scratching: 30, control: 30)

Computer-generated randomization table (Research Randomizer Version 4.0 software) in a 1: 1 ratio

Not reported

Not reported

Yes

Pregnancy (definition not reported)

Not reported

Yes

Attempted; No response

Eskew et al., (2019) [35], USA, single center, Journal of Assisted Reproduction and Genetics

September 2013- July 2017

100 (endometrial scratching: 53, control: 47)

Computer-generated block randomization

Consecutively numbered sealed opaque envelopes

Double-blind

Yes

Clinical pregnancy Live birth Miscarriage (definitions not reported)

5T32HD055172-09 and UL1 TR002345

Not reported

Attempted; No response

Frantz et al., (2019) [36], France, multicenter, Human Reproduction

February 2010- July 2014

191 (endometrial scratching: 98, control: 93)

Randomization sequence was generated using SAS Software and was stratified by center with a 1: 1 allocation using random block sizes of 4 and 6

Allocation using random block sizes of 4 and 6

Non-blind

Yes

Clinical pregnancy (at least one intrauterine gestational sac with embryonic cardiac activity)

Ministère de la Santé Français

Yes

Yes

Gurgan et al., (2019) [37], Tuukey, single center, Reproductive Biomedicine Online

February 2015- October 2017

305 (endometrial scratching: 153, control: 152)

Computer-generated random number sequence (1: 1 simple randomization)

Not reported

Not reported

No

Clinical pregnancy (at least one gestational sac with embryonic cardiac activity on U/S) Live birth (definition not reported) Implantation (gestational sacs on U/S)

Not reported

Yes, retrospectively

Attempted; No response

Hilton et al., (2019) [38], Canada, multicenter, Archives of Gynecology and Obstetrics

May 2013- May 2015

51 (endometrial scratching: 25, control: 26)

SAS System for Windows- generated numbers accessed electronically (1: 1 ration, stratification by the study center)

Web-based randomization system

Non-blind

Yes

Clinical pregnancy (documented embryonic cardiac activity 5 weeks after implantation)

Ferring Inc.,Canada

Yes

Yes

Lensen et al., (2019) [5, 6], (New Zeeland, UK, Belgium, Sweden), multicenter, New England Journal of Medicine

June 2014- June 2017

1364 (endometrial scratching: 690, control: 674)

Block randomization of two different sizes between 6 and 16 repeating in random order (1: 1 ratio, stratification according to recruiting site and to whether a fresh-ET or frozen-ET)

Block randomization of two different sizes between 6 and 16 repeating in random order

Non-blind

Yes

Live birth (Definition not reported)

University of Auckland and others

Yes

Attempted; No response

Olesen et al., (2019) [39], Denmark, multicenter, Fertility Sterility

February 2014- December 2017

304 (endometrial scratching: 151, control: 153)

Randomization into blocks of 10 for each participating clinic (1: 1 ratio, according to an Internet-based randomization list)

Consecutively numbered opaque sealed envelopes

Non-blind

Yes

Clinical pregnancy (Definition not reported)

Health Research Fund of the Central Denmark

Yes

Attempted; No response

Berntsen et al., (2020) [40], Denmark, double center, European Journal of Obstetrics and Gynecology and Reproductive Biology

2013- 2018

229 (endometrial scratching: 122, control: 107)

Third-party computer randomization (simple 1: 1 randomization, without using block randomization or stratification)

Not reported

Non-blind

Yes

Positive pregnancy test (serum β-hCG>10 IU/l on day 13–15 after ET)

Department of Gynaecology and Obstetrics at Copenhagen University Hospital Hvidovre

Yes

Attempted; No response

Izquierdo Rodriguez et al., (2020) [41], Spain, single center, Reproductive Sciences

January 2017-October 2018 (follow-up until October 2019)

352 (endometrial scratching: 176, control: 176)

Simple randomization by web-based program

Not reported

Non-blind

Yes

Clinical pregnancy per ET (intrauterine gestational sac on TVS at approximately 6 weeks of gestation)

ProcreaTec Fertility Center

Yes

Attempted; No response

Mackens et al. (2020) [42], Belgium, single center, Human Reproduction

3 April 2014- 8 October 2017

200 (endometrial scratching:100, control:100)

Computer-generated randomization

list

Sequentially numbered opaque sealed envelopes

Not reported

Yes

Clinical pregnancy (gestational sac on TVS at 7 weeks of gestation)

Fonds Wetenschappelijk Onderzoek’ (FWO, Flanders, Belgium)

Yes

Yes

Tang et al., (2020) [43], China, single center, Journal of Obstetrics and Gynaecology Research

October 2017- February 2018

220 (endometrial scratching: 110, control: 110)

Manual randomization (sealed envelopes) (details on how the randomization list was generated were not provided)

Sealed envelopes

Non-blind

Yes

Clinical pregnancy (gestational sac on TVS approximately 5 weeks after ET) Live birth (deliveries that resulted in a live born after ET) Implantation (gestational sacs on TVS)

Funded by HeFei Municipal Health Planning Commission, Key Research and Development Project of AnHui Province, Key Talents of Maternal and Child Health in Jiangsu Province and Science Technology Innovation Project of Suzhou

Yes

No

Van Hoogenhuijze et al., (2020) [8, 9], Netherlands, multicenter, Human reproduction

January 2016- July 2018

946 (endometrial scratching: 472, control :474)

Randomization 1: 1 centrally located, non-center-stratified by a web-based programme (ALEA Clinical B.V.) using randomly permuted blocks with block size varying randomly between two and four

Randomly permuted blocks with block size varying randomly between two and four

Non-blind

Yes

Live birth (delivery of at least one live fetus after 24 weeks of gestation)

Dutch organisation for funding of healthcare research ZonMW. The sponsor of the SCRaTCH study was the University Medical

Centre Utrecht (UMCU)

Yes

Yes

Metwally et al., (2021) [44], UK, multicenter, Human Reproduction

4th July,2016- 24th October 2018 (follow-up until 24th October, 2019)

1048 (endometrial scratching: 523, control: 525

Randomization sequence generated by the trial statistician using a computer via a web-based system. 1: 1 stratified block randomization was used, with randomly permuted masked blocks of sizes 2, 4, and 6 stratified by site and planned IVF/ICSI (antagonist or long)

Web-based randomization system with restricted access rights that concealed allocation

Non-blind

Yes

Live birth (live birth beyond the 24th week of pregnancy)

National Institute for Health Research

Yes

No

Zahiri et al., (2021) [45], Iran, single center, Galen Medical Journal

Not reported

228 (endometrial scratching: 114, control: 114)

Not reported

Not reported

Not reported

No

Fetal heart activity (assessed via U/S)

Multiple pregnancies (assessed via U/S) Abortion (loss of gestational products before the 12th week of gestation)

Vice-Chancellorship of Research and Technology, Guilan University of Medical Sciences

Yes

Attempted; No response

Izquierdo et al., (2022) [46], Spain, single center, Journal of Gynecology Obstetrics and Human Reproduction

January 2017- October 2018 (follow-up until October 2019)

352 (endometrial scratching: 176, control: 176)

Simple randomization by web-based program

Not reported

Non-blind

Yes

Live birth (birth of a living baby beyond the 24th week of pregnancy)

ProcreaTec Fertility Center; Analysis of cumulative Live birth rates

did not receive specific funding

Yes

Attempted; No response

Noori et al., (2022) [47], Iran, single center, Journal of Obstetrics and Gynaecology

May 2019- December 2019

100 (endometrial scratching: 50, control: 50)

Sealed envelopes were used as the means of randomization for allocating them into the study groups (details on how the randomization list was generated were not provided)

Sealed envelopes

Not reported

Yes

Chemical pregnancy (β-hCG positive test)

Clinical pregnancy (at least 1 intrauterine gestational sac with embryonic cardiac activity)

Research Department of Zahedan University of Medical Sciences

Yes (retrospectively)

Attempted; No response

Turktekin et al., (2022) [48], Turkey, single center, Annals of Clinical and Analytical Medicine

2019-2020

60 (endometrial scratching: 30, control: 30)

Not reported

Not reported

Not reported

Not reported

Clinical pregnancy rate (evidence of a gestational sac, confirmed by U/S at the 4th week of transfer)

Live birth (delivery of a live fetus after 24 completed weeks of gestational age) Serum β-hCG levels (measured in all patients on the 12th day of embryo transfer) Miscarriage (loss of fetus before 20 weeks of gestation)

None

Not reported

Attempted; No response

  1. ET Embryo transfer, FET Frozen-thawed embryo transfer, hCG Human chorionic gonadotrophin, TVS Transvaginal scan, U/ Ultrasonographic scan